[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-malignant-solid-neoplasm\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-malignant-solid-neoplasm":35},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,54,0,25,[9,56,89,110,142,162,192,302,341,362,380,399,418,440,458,477,501,530,540,564,585,603,638,658,674],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":44,"lastUpdatePostDateStruct":45,"startDateStruct":48,"completionDateStruct":50,"leadSponsor":52,"locationsCount":55},"100053568","phase-1-testing-the-safety-of-the-combination-of-anti-cancer-drugs-cx-5461-pidnarulex-and-trastuzumab-deruxtecan-t-dxd-for-human-epidermal-growth-factor-receptor-2-her2-positive-solid-tumors-and-breast-cancer-100053568",false,"NCT07137416","Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer","Phase 1b Study of Pidnarulex and Trastuzumab Deruxtecan in Patients With HER2 Expressing Solid Tumors","Inclusion Criteria:\n\n* DOSE ESCALATION PHASE ONLY: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* DOSE EXPANSION PHASE ONLY: Participants must have histologically or cytologically confirmed invasive breast cancer, with either locally advanced or metastatic disease\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CX-5461 (pidnarulex) in combination with T-DXd in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL\n\n  * No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment\n* Platelets ≥ 100,000\u002FmcL\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (or ≤ 2 × institutional ULN in patients with documented Gilbert's syndrome)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) ≤ 3 × institutional ULN (or ≤ 5 × ULN in patients with liver metastases)\n* International normalized ratio (INR)\u002Fprothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN\n* Glomerular filtration rate (GFR) ≥ 60 mL\u002Fmin\u002F1.73 m\\^2 (using the Cockcroft-Gault equation for participants with creatinine levels above institutional ULN)\n* Patients must have had at least one prior line of cytotoxic chemotherapy. Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy. Patients must not have progressed on a prior anthracycline in the metastatic setting. Receipt of anthracycline in the (neo)adjuvant setting is allowed, provided that disease recurrence occurred later than 6 months after the completion of treatment\n* Prior poly (ADP-ribose) polymerase (PARP) inhibition is allowed\n* No specific germline mutation is required\n* DOSE ESCALATION PHASE ONLY:\n\n  * HER2-positive (IHC 3+) solid cancers,\n  * HR+ HER2 positive\u002Flow\u002Fultralow breast cancer or triple negative breast cancer (TNBC) HER2-low breast cancer, with HER2 positive defined by the current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines,\n  * HER2-low, with HER2-low defined as IHC 2+\u002Fin situ hybridization (ISH)-, IHC 1+\u002FISH-, or IHC 1+\u002FISH untested\n* DOSE EXPANSION PHASE ONLY:\n\n  * Either the primary invasive tumor and\u002For the metastasis must be:\n\n    * HER2-low, with HER2-low defined as IHC 2+\u002FISH-, IHC 1+\u002FISH-, or IHC 1+\u002FISH untested. Any estrogen receptor (ER) and progesterone receptor (PR) expression is permitted but must be known, or\n    * HR+ HER2-ultralow defined as IHC 0 with membrane staining\n* Participants must have at least one lesion that is not within a previously radiated field that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Bone lesions are not considered measurable by definition. Biopsy of the lesion that will be used for disease evaluation (measurable disease) is not allowed in the dose expansion portion of this study\n* Peripheral neuropathy grade ≤ 1\n* Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days before randomization\u002Fenrollment\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* The effects of CX-5461 (pidnarulex) and T-DXd on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) 14 days prior to study entry and for the duration of study participation and for at least 7 months (women of childbearing potential \\[WOCBP\\] only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking CX-5461 (pidnarulex) and T-DXd and for 7 months after cessation of treatment. Men treated or enrolled on this protocol must also agree to use adequate contraception 14 days prior to the study, for the duration of study participation, and 6 months after completion of CX-5461 (pidnarulex) and T-DXd administration\n* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\[FSH\\] \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) or on ovarian suppression are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method\n* Male patients must not freeze or donate sperm starting at screening and throughout the study period, and at least 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study\n* Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives (LAR) may sign and give informed consent on behalf of study participants\n* Patients who have had chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic radiation therapy). These patients will be excluded because T-DXd is known to increase the risk of developing pneumonitis\n\nExclusion Criteria:\n\n* Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, have current ILD, or where there is suspected ILD that cannot be ruled out by imaging at screening. These patients will be excluded because T-DXd is known to increase the risk of developing ILD and pneumonitis\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy at the time of screening. These patients will be excluded because T-DXd is known to increase the risk of developing ILD and pneumonitis\n* Patients who have had chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer) within 3 weeks (2 weeks or five half-lives, whichever is longer for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents), weekly paclitaxel; 6 weeks for nitrosoureas or mitomycin C. These patients will be excluded to allow for recovery of toxicities related to chemotherapy and minimize risk of drug interactions\n* Patients who have had cancer immunotherapy including monoclonal antibody therapy within 4 weeks\n* Patients who have had a major surgery within 4 weeks\n* Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade ≤ 1 or baseline. Patients with chronic grade 2 toxicities may be eligible (e.g., grade 2 chemotherapy-induced neuropathy). Patients should no longer be symptomatic nor require treatment with corticosteroids or anticonvulsants and must have recovered from the acute toxic effect of radiotherapy\n* Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of CX-5461 (pidnarulex) will be determined based on their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from participation in the trial. A list of agents that interact with CYP450 isoenzymes is provided\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CX-5461 (pidnarulex), T-DXd, or the inactive ingredients in the drug products, including patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies\n* Patients with a corrected QT interval (QTc) prolongation to \\> 470 ms (females) or \\> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)\n* Patients with clinically significant corneal disease, cicatricial conjunctivitis or active ocular surface disease in the opinion of the investigator\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because CX-5461 (pidnarulex) and T-DXd are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with CX-5461 (pidnarulex) and T-DXd, breastfeeding should be discontinued if the mother is treated with CX-5461 (pidnarulex) and T-DXd and avoided for 7 months after the last dose","ALL","18 Years",{"count":20,"type":21},36,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast cancer and other solid tumors that express varying levels of a protein called HER2 and that has spread from where it first started (primary site) to other places in the body (metastatic), that cannot be removed by surgery (unresectable), or that has spread to nearby tissue or lymph nodes (locally advanced). Pidnarulex is an enzyme inhibitor that causes cell death and prevents tumor cell growth. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving pidnarulex in combination with trastuzumab deruxtecan may be safe, tolerable and\u002For effective in treating patients with metastatic, unresectable, or locally advanced HER2-expressing breast cancer or other solid tumors.",[27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Invasive Breast Carcinoma","Locally Advanced Breast Carcinoma","Metastatic Breast Carcinoma","Metastatic HER2-Low Breast Carcinoma","Metastatic HER2-Positive Breast Carcinoma","Metastatic Hormone Receptor-Positive Breast Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Triple-Negative Breast Carcinoma","Unresectable Breast Carcinoma","Unresectable HER2-Low Breast Carcinoma","Unresectable HER2-Positive Breast Carcinoma","Unresectable Hormone Receptor-Positive Breast Carcinoma","Unresectable Malignant Solid Neoplasm","Unresectable Triple-Negative Breast Carcinoma","RECRUITING","2026-07-10",{"date":46,"type":47},"2026-07-13","ACTUAL",{"date":49,"type":21},"2026-10-05",{"date":51,"type":21},"2028-01-10",{"name":53,"class":54},"National Cancer Institute (NCI)","NIH",2,{"id":57,"slug":58,"hasResults":12,"nctId":59,"briefTitle":60,"officialTitle":61,"acronym":4,"eligibilityCriteria":62,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":63,"targetDuration":4,"studyType":22,"phases":65,"briefSummary":67,"conditions":68,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":80,"lastUpdatePostDateStruct":81,"startDateStruct":83,"completionDateStruct":85,"leadSponsor":87,"locationsCount":88},"100482618","phase-2-targeted-therapy-directed-by-genetic-testing-in-treating-patients-with-locally-advanced-or-advanced-solid-tumors-the-combomatch-screening-trial-100482618","NCT05564377","Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial","Molecular Analysis for Combination Therapy Choice (ComboMATCH)","Inclusion Criteria:\n\n* Patient must have measurable disease\n* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 OR patient must have Lansky performance status of \\>= 50% or Karnofsky performance status of \\>= 50%\n* Patient must be deemed potentially eligible for a ComboMATCH Treatment Trial as assessed by the enrolling provider\n* All patients must have sequencing results available from a National Cancer Institute (NCI) credentialed Designated Laboratory (DL)\n* Patients must have locally advanced or advanced histologically documented solid tumors requiring therapy and meet one of the following criteria:\n\n  * Patients must have progressed on at least one line of standard systemic therapy OR\n  * Patients whose disease has no standard treatment that has been shown to prolong overall survival\n* Patient must meet one of the following requirements:\n\n  * Patients 18 years and older who have tumor amenable to minimal risk image-guided or direct vision biopsy and must be willing and able to undergo a tumor biopsy to obtain samples for research if the patient is to enroll in a ComboMATCH treatment trial OR\n  * Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:\n\n    * Tissue must have been collected within 12 months prior to registration to the EAY191 Registration Trial\n    * Patient must not have had a Response Evaluation Criteria in Solid Tumors (RECIST) response (complete response \\[CR\\] or partial response \\[PR\\]) to any intervening therapy after collection of the tissue\n    * Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available OR\n  * Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:\n\n    * Formalin-fixed paraffin-embedded tumor tissue block(s) or slides must be available\n  * NOTE: See specific ComboMATCH Treatment Trial protocol for tissue collection and management instructions. Performance of the mandatory research biopsy or submission of pre-trial formalin-fixed paraffin-embedded (FFPE) and collection and submission of the blood specimens for the integrated studies will be performed under the consent authority of the specific treatment trial protocol to which the patient is registered. No procedures to collect specimens for research only are to be performed for patients registered to the EAY191 Registration Trial only\n* NOTE: Each ComboMATCH Treatment Trial contains specific eligibility criteria. If patient is found to not be eligible for the assigned ComboMATCH Treatment Trial, indication of ineligibility will trigger re-evaluation and potential assignment to another Treatment Trial",{"count":64,"type":21},2900,[66],"PHASE2","This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.",[69,27,28,70,71,72,35,73,74,75,76,77,78,79,41],"Advanced Malignant Solid Neoplasm","Locally Advanced Malignant Solid Neoplasm","Malignant Female Reproductive System Neoplasm","Metastatic HER2-Negative Breast Carcinoma","Recurrent Endometrial Carcinoma","Recurrent Fallopian Tube Carcinoma","Recurrent Malignant Female Reproductive System Neoplasm","Recurrent Malignant Solid Neoplasm","Recurrent Ovarian Carcinoma","Recurrent Primary Peritoneal Carcinoma","Unresectable HER2-Negative Breast Carcinoma","2026-07-01",{"date":82,"type":47},"2026-07-02",{"date":84,"type":47},"2023-04-07",{"date":86,"type":21},"2030-07-01",{"name":53,"class":54},481,{"id":90,"slug":91,"hasResults":12,"nctId":92,"briefTitle":93,"officialTitle":94,"acronym":4,"eligibilityCriteria":95,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":96,"targetDuration":4,"studyType":22,"phases":98,"briefSummary":99,"conditions":100,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":101,"lastUpdatePostDateStruct":102,"startDateStruct":104,"completionDateStruct":106,"leadSponsor":108,"locationsCount":109},"100492051","phase-1-studying-the-safety-and-determining-the-optimal-dose-of-novobiocin-in-patients-with-tumors-that-have-alterations-in-dna-repair-genes-100492051","NCT05687110","Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes","A Phase 1 Study of the Polymerase Theta (POLθ) Inhibitor Novobiocin in BRCA- Mutant and Other DNA Damage Repair-Deficient Solid Tumors","Inclusion Criteria:\n\n* Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* Patients must have histologically confirmed solid tumor with a known pathogenic mutation in BRCA1\u002F2, PALB2, RAD51C, RAD51D, ATM, BARD1, BLM, BRIP1, CDK12, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN (NBS1), RAD50 and RAD51B as confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified method. Patients with alterations defined only by germline testing are eligible. Other qualifying HRD alterations may be considered if approved by the principal investigator and the Cancer Therapy Evaluation Program (CTEP) monitor\n* Any number of prior therapy regimens is allowed\n* Patients with cancers for which PARP inhibitors have been approved as standard-of-care must have received a PARP inhibitor prior to enrollment on this study. Other patients may be either PARP inhibitor-naïve (i.e., never have received a PARP inhibitor) or have disease that is PARP inhibitor-resistant (i.e., disease that has progressed radiologically based on Response Evaluation Criteria in Solid Tumors \\[RECIST\\] 1.1 while receiving any PARP inhibitor)\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of novobiocin in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group Performance (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%)\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Leukocytes \\>= 3,000\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Total bilirubin =\\\u003C 1.5 × institutional upper limit of normal (ULN)\n* Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine transferase (ALT)(serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 1.5 × institutional ULN\n* Glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin (via the chronic kidney disease epidemiology \\[CKD-EPI\\] glomerular filtration rate estimation)\n* Fridericia's formula-corrected QT interval (QTcF) =\\\u003C 480 ms\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, stable and off steroids for 1 month\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the patient is asymptomatic and the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* Patients must have tumors amenable to biopsies, and be willing to undergo biopsies at two time points (pre- and on-treatment)\n* The effects of novobiocin on the developing human fetus are unknown. For this reason and because polymerase theta (POLtheta) inhibitor agents have the potential to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of novobiocin administration. Effective contraception is defined as a method that achieves a failure rate of less than 1% per year when used consistently and correctly. (Note: Because of a concern for decreased effectiveness of estrogen-containing oral agents when given with novobiocin, barrier methods and abstinence are the preferred methods for contraception). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and\u002For family member available will also be eligible\n\nExclusion Criteria:\n\n* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to novobiocin\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4\u002F5 are ineligible. Patients receiving any medications or substances that are known to be substrates of breast cancer resistance protein (BCRP\u002FABCG2) and\u002For organic anion transporting polypeptides (OATP1B1, OATP1B3 and OATP2B1) and\u002For organic anion transporters (OAT1 and OAT3) within 14 days prior to the first dose of study drug are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients using herbal\u002Fdietary supplements with known hepatotoxicity risk are ineligible\n* Patients receiving concurrent medications associated with a risk of corrected QT interval (QTc) prolongation and\u002For Torsades de Pointes are not allowed within 14 days of initiation of study treatment. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference such as CredibleMeds or Lexicomp. Drugs listed in the \"drugs to avoid in CLQTS (congenital long QT syndrome)\" and \"known risk of TdP (torsade de pointes)\" should be excluded. Granisetron is an acceptable antiemetic on this study. If a patient must take ondansetron, they may NOT take any other concomitant agents which might impact their QTc\n* Patients must have UGT1A1 testing at screening. Patients homozygous for A(TA)7TAA in the promoter region (also known as UGT1A1 \\*28), homozygous for the G71R allele (also known as UGT1A1\\*6), or with compound alterations of \\*28 and \\*6, are excluded as they are at risk for further reduction of UGT1A1 activity that may disrupt bilirubin clearance\n\n  * UGT1A1 testing must address both \\*28 and \\*6 alterations\n* Patients with uncontrolled intercurrent illness. Additionally, patients with acute liver disease, poorly controlled liver disease, or cirrhosis are excluded\n* Patients with (known) active or poorly controlled alcohol use disorder are excluded\n* Pregnant women are excluded from this study because novobiocin is a POLtheta inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with novobiocin, breastfeeding should be discontinued if the mother is treated with novobiocin",{"count":97,"type":21},43,[24],"This phase I trial tests the safety, side effects, and best dose of novobiocin in treating cancer patients with alterations in deoxyribonucleic acid (DNA) repair genes. Novobiocin is an antibiotic that blocks the activity of a protein called DNA polymerase theta, which helps repair DNA that has become damaged as cells grow and divide. Cancer cells that cannot repair their damaged DNA die. This medication may help shrink or stabilize cancer with a mutation in DNA repair genes.",[35,41],"2026-06-27",{"date":103,"type":47},"2026-06-30",{"date":105,"type":47},"2023-07-06",{"date":107,"type":21},"2026-09-01",{"name":53,"class":54},23,{"id":111,"slug":112,"hasResults":12,"nctId":113,"briefTitle":114,"officialTitle":115,"acronym":4,"eligibilityCriteria":116,"healthyVolunteers":117,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":118,"targetDuration":4,"studyType":22,"phases":120,"briefSummary":122,"conditions":123,"keywords":126,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":131,"lastUpdatePostDateStruct":132,"startDateStruct":134,"completionDateStruct":136,"leadSponsor":138,"locationsCount":141},"100402096","mobile-health-application-pact-to-improve-engagement-in-advance-care-planning-100402096","NCT04515810","Mobile Health Application (PACT) to Improve Engagement in Advance Care Planning","Planning Advance Care Together (PACT) to Improve Engagement in Advance Care Planning","Inclusion Criteria:\n\n* PATIENT: Diagnosis of poor prognosis advanced cancer defined as locally advanced or metastatic solid cancer and\u002For disease progression following at least first line systemic therapy and\u002For relapsed or refractory hematologic cancer.\n* PATIENT: Have internet access through a computer or a mobile device; the principal investigator (PI) will ensure that those who have access to a computer or mobile device have access to a computer or mobile device with internet access to ensure they can complete study procedures.\n* PATIENT: The ability to provide informed consent.\n* PATIENT: Identification of a loved support person if one is available; patients who are unable to identify a support person willing to participate with them will be allowed to continue in the study on their own.\n* PATIENT: 18 years of age or older.\n* SUPPORT PERSON: The person (family member or friend) whom the patient indicates being a support person.\n* SUPPORT PERSON: English speaking.\n* SUPPORT PERSON: 18 years of age or older and able to provide informed consent.\n* PROVIDER: Current clinical practice and\u002For research with advanced cancer patients.\n* PROVIDER: A history of 3+ years working with advanced cancer patients.\n* PROVIDER: 18 years of age or older. Providers across disciplines (e.g., social work, oncology) will be enrolled.\n\nExclusion Criteria:\n\n* PATIENT: Not fluent in English.\n* PATIENT: Severely cognitively impaired (as measured by Short Portable Mental Status Questionnaire scores of \\>= 6) to be delivered by trained study research staff during screening.\n* PATIENT: Too ill or weak to complete the interviews (as judged by the interviewer).\n* PATIENT: Currently receiving hospice at the time of enrollment.\n* PATIENT: Children and young adults under age 18.",true,{"count":119,"type":21},400,[121],"NA","This clinical trial tests a new mobile health application (app) called Planning Advance Care Together (PACT) to help people with cancer talk about and plan for advance care planning (the care they would want if they were unable to communicate) with their loved ones and doctors. The development of the PACT mobile app may help future patients incorporate their social network (typically, but not exclusively, family) into the advance care planning process.",[70,35,124,125],"Recurrent Hematologic Malignancy","Refractory Hematologic Malignancy",[127,128,129,130],"Advance Care Planning","Advance Directives","End-of-Life","Cancer","2026-06-24",{"date":133,"type":47},"2026-06-26",{"date":135,"type":47},"2025-02-18",{"date":137,"type":21},"2026-12-31",{"name":139,"class":140},"Fred Hutchinson Cancer Center","OTHER",4,{"id":143,"slug":144,"hasResults":12,"nctId":145,"briefTitle":146,"officialTitle":147,"acronym":4,"eligibilityCriteria":148,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":149,"targetDuration":4,"studyType":22,"phases":150,"briefSummary":151,"conditions":152,"keywords":4,"overallStatus":153,"whyStopped":4,"lastUpdateSubmitDate":154,"lastUpdatePostDateStruct":155,"startDateStruct":156,"completionDateStruct":157,"leadSponsor":159,"locationsCount":161},"100644542","magnetic-resonance-guided-stereotactic-body-radiation-therapy-for-the-treatment-of-metastatic-solid-tumors-one-shot-trial-100644542","NCT07671768","Magnetic Resonance-Guided Stereotactic Body Radiation Therapy for the Treatment of Metastatic Solid Tumors, ONE SHOT Trial","ONE SHOT: Single-Fraction Adaptive MR-Guided Radiation Therapy for Metastatic Solid Tumors","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) 0-2\n* Histologically confirmed metastatic solid tumor (any primary site)\n* 1-3 metastases ≤ 5 cm each located outside the brain and spine\n* Lesions treatable at 25-30 Gy × 1 fraction with MR guidance\n* No overlapping prior radiation\n* Absolute neutrophil count (ANC) \\> 1.5 cell\u002Fmm\\^3\n* Hemoglobin (Hgb) \\> 8.0 gm\u002FdL\n* Platelet (PLT) \\> 150,000\u002Fmm\\^3\n* Total bilirubin \\\u003C or equal to 1.5 x upper limit of normal\n* Aspartate aminotransferase (AST) \\\u003C or equal to three times upper limit of normal\n* Alanine aminotransferase (ALT) \\\u003C or equal to three times upper limit of normal\n* Informed consent obtained\n\nExclusion Criteria:\n\n* Uncontrolled infection or major comorbidity\n* Pregnant or breastfeeding\n* MRI contraindication\n* Life expectancy \\\u003C 3 months",{"count":7,"type":21},[121],"This clinical trial studies the side effects of magnetic resonance (MR)-guided stereotactic body radiation therapy (SBRT) and to see how well it works in treating patients with solid tumors that have spread from where they first started (primary site) to other places in the body (metastatic). SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body. The total dose of radiation is divided into smaller doses given over 1-5 days. This type of radiation therapy helps spare normal tissue. During MR-guided SBRT, MR imaging is used to define and localize the area to be treated and provide more accurate delivery. This allows the treatment to be given over one day. MR-guided SBRT may be safe, tolerable, and\u002For effective in treating patients with metastatic solid tumors. Tumors in the central nervous system will not be treated on this study.",[35],"NOT_YET_RECRUITING","2026-06-23",{"date":133,"type":47},{"date":80,"type":21},{"date":158,"type":21},"2038-07-01",{"name":160,"class":140},"Jonsson Comprehensive Cancer Center",1,{"id":163,"slug":164,"hasResults":12,"nctId":165,"briefTitle":166,"officialTitle":167,"acronym":4,"eligibilityCriteria":168,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":169,"targetDuration":4,"studyType":22,"phases":171,"briefSummary":173,"conditions":174,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":182,"lastUpdatePostDateStruct":183,"startDateStruct":185,"completionDateStruct":187,"leadSponsor":189,"locationsCount":191},"100554543","phase-3-testing-longer-duration-radiation-therapy-versus-the-usual-radiation-therapy-in-patients-with-cancer-that-has-spread-to-the-brain-100554543","NCT06500455","Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain","Phase III Trial of Single Fraction Stereotactic Radiosurgery (SRS) Versus Fractionated SRS (FSRS) for Intact Brain Metastases","Inclusion Criteria:\n\n* Pathologically (histologically or cytologically) proven diagnosis of one of the following solid tumor malignancies within 5 years prior to registration:\n\n  * Non-small cell lung cancer\n  * Melanoma\n  * Breast cancer\n  * Renal cell carcinoma\n  * Gastrointestinal cancer\n  * If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest\u002Fabdomen\u002Fpelvis, positron emission tomography \\[PET\\]\u002FCT, etc.) is required\n* Patients must have at least 1 and up to 8 total intact brain metastases detected on a contrast-enhanced MRI performed ≤ 21 days prior to registration\n* At least 1 of the up to 8 lesions must be a study eligible lesion, defined as lesion with a maximum diameter as measured on any orthogonal plane (axial, sagittal, coronal) of ≥ 1.0 cm and ≤ 3.0 cm\n* All brain metastases must be located outside of the brainstem and ≥ 5 mm from the optic nerves or optic chiasm and ≤ 3.0 cm in maximum dimension\n\n  * Note: brainstem metastases per the MRI within 21 days of registration are an exclusion criterion; however, if the MRI used for treatment planning performed within 7 days of SRS\u002FFSRS reveals a brainstem metastasis, the patient remains eligible if the patient is considered an appropriate radiosurgery candidate per the local investigator\n* Patients must have a diagnosis-specific graded prognostic assessment ≥ 1.5\n* No more than 2 lesions planned for resection if clinically indicated\n* No known leptomeningeal disease (LMD)\n\n  * Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive cerebrospinal fluid (CSF) cytology and\u002For unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion\n* Age ≥ 18 years\n* Karnofsky performance status (KPS) ≥ 60\n* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal\n* No prior radiotherapy to the brain (partial or whole brain irradiation, SRS, FSRS, or prophylactic cranial irradiation \\[PCI\\])\n* New York Heart Association Functional Classification II or better (NYHA Functional Classification III\u002FIV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)\n* No active infection currently requiring intravenous (IV) antibiotic management\n* No hepatic insufficiency resulting in clinical jaundice and\u002For coagulation defects\n* No chronic obstructive pulmonary disease exacerbation or other acute respiratory illness precluding study therapy",{"count":170,"type":21},269,[172],"PHASE3","This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.",[28,31,175,176,177,35,178,179,180,181],"Metastatic Digestive System Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Neoplasm in the Brain","Metastatic Melanoma","Metastatic Renal Cell Carcinoma","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","2026-06-22",{"date":184,"type":47},"2026-06-25",{"date":186,"type":47},"2024-12-12",{"date":188,"type":21},"2028-06-30",{"name":190,"class":140},"NRG Oncology",270,{"id":193,"slug":194,"hasResults":12,"nctId":195,"briefTitle":196,"officialTitle":197,"acronym":198,"eligibilityCriteria":199,"healthyVolunteers":12,"sex":17,"minAge":200,"maxAge":4,"enrollmentInfo":201,"targetDuration":4,"studyType":22,"phases":203,"briefSummary":204,"conditions":205,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":294,"lastUpdatePostDateStruct":295,"startDateStruct":296,"completionDateStruct":298,"leadSponsor":300,"locationsCount":161},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol\n\n  * NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test =\\\u003C 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained =\\\u003C 28 days prior to pre-registration:\n\n  * Hemoglobin \\>= 9.0 g\u002FdL (Must be \\>= 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 or \\>= 1.5 X 10\\^9\u002FL\n  * Platelet count \\>= 100,000\u002Fmm\\^3 or \\>= 100 X 10\\^9\u002FL (Must be \\>=7 days after most recent transfusion)\n  * Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) =\\\u003C 3 x ULN or =\\\u003C 5 x ULN with liver metastases\n  * Creatinine =\\\u003C 1.5 x ULN OR calculated creatinine clearance must be \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see specified limits for inclusion) or NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease \\>= 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor \\>= 2 cm on pre-surgery evaluation imaging (residual disease \\>= 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to proceed with surgery and provide tissue specimens for complete exome and transcriptome sequencing\n\n  * NOTE: Patients who had sequencing under certain Mayo IRB protocols and neoantigens identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test ≤7 days prior to pre-registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive \\>= 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction =\\\u003C 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke =\\\u003C 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in =\\\u003C 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major Surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n  * Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002Fribonucleic acid (RNA)\u002Fdeoxyribonucleic acid (DNA) quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are \\>= 2 cores with passing cellularity; (3) \\>= 30% of tumor RNA with fragment sizes are \\>= 200 base pairs (DV200 \\>= 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Requirement for systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in","16 Years",{"count":202,"type":21},132,[24,66],"This phase I\u002FII trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.",[27,206,207,208,28,209,210,211,212,213,214,215,216,217,218,219,220,221,222,223,224,225,226,227,70,228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,176,35,178,245,179,246,36,247,248,249,250,251,252,253,254,255,256,257,258,259,260,261,262,263,264,265,266,267,180,181,268,269,270,271,272,273,274,275,276,277,278,279,280,281,282,283,41,284,285,286,287,42,288,289,290,291,292,293],"Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Lung Non-Small Cell Carcinoma","Locally Advanced Melanoma","Locally Advanced Merkel Cell Carcinoma","Locally Advanced Renal Cell Carcinoma","Locally Advanced Skin Squamous Cell Carcinoma","Locally Advanced Triple-Negative Breast Carcinoma","Locally Advanced Unresectable Breast Carcinoma","Locally Advanced Unresectable Cervical Carcinoma","Locally Advanced Unresectable Gastric Adenocarcinoma","Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma","Locally Advanced Unresectable Renal Cell Carcinoma","Locally Advanced Urothelial Carcinoma","Metastatic Cervical Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Merkel Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Urothelial Carcinoma","Skin Squamous Cell Carcinoma","Stage III Cervical Cancer AJCC v8","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IIIA Cervical Cancer AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIB Cervical Cancer AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IIIB Lung Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Lung Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IVA Cervical Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Cervical Cancer AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Stage IVB Lung Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Triple-Negative Breast Carcinoma","Unresectable Cervical Carcinoma","Unresectable Endometrial Carcinoma","Unresectable Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Head and Neck Squamous Cell Carcinoma","Unresectable Hepatocellular Carcinoma","Unresectable Lung Non-Small Cell Carcinoma","Unresectable Melanoma","Unresectable Merkel Cell Carcinoma","Unresectable Renal Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Urothelial Carcinoma","Breast Adenocarcinoma","Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","2026-06-18",{"date":154,"type":47},{"date":297,"type":47},"2022-03-31",{"date":299,"type":21},"2028-03-31",{"name":301,"class":140},"Mayo Clinic",{"id":303,"slug":304,"hasResults":12,"nctId":305,"briefTitle":306,"officialTitle":307,"acronym":4,"eligibilityCriteria":308,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":309,"targetDuration":4,"studyType":22,"phases":310,"briefSummary":311,"conditions":312,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":294,"lastUpdatePostDateStruct":335,"startDateStruct":336,"completionDateStruct":338,"leadSponsor":340,"locationsCount":141},"100404756","phase-2-measuring-the-effects-of-talazoparib-in-patients-with-advanced-cancer-and-dna-repair-variations-100404756","NCT04550494","Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations","A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response","Inclusion Criteria:\n\n* Adult patients with solid tumors and documented germline or somatic aberrations in genes involved in DNA damage response (DDR) and whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options. Molecular testing performed at an National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) (NCT02465060) study-designated Clinical Laboratory Improvement Act (CLIA) laboratory or at Myriad Genetics, GeneDx, Invitae, or the Frederick National Laboratory for Cancer Research (FNLCR) Molecular Characterization Laboratory (MoCha) will be acceptable for determination of eligibility\n* Patients with the following germline or somatic genetic aberrations will be eligible based on compelling preclinical and\u002For clinical data suggesting that these deleterious mutations confer sensitivity to PARP inhibitors; no more than 6 patients (across both cohorts) with an eligibility mutation in any one gene will be enrolled\n\n  * Deleterious BRCA1 or BRCA2 mutations\n  * Loss of function mutations (including novel loss of function frameshift or nonsense mutations) in the following Fanconi anemia genes: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN\n  * A known functional mutation (including novel loss of function frameshift or nonsense mutations) in any of the following DDR genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, CDK12, CHK1, CHK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L\n* Age \\>= 18 years of age\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2\n* Life expectancy of greater than 3 months\n* Leukocytes \\>= 3,000\u002FmcL\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Hemoglobin \\>= 10 g\u002FdL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (=\\\u003C 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) \u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 3 x institutional upper limit of normal\n* Creatinine =\\\u003C 1.5 x institutional upper limit of normal OR Creatinine clearance (CrCl) \\>= 60 mL\u002Fmin\u002F1.73m\\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL\u002Fmin\u002F1.73m\\^2\n* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \\>= 20 mm (\\>= 2 cm) by chest x-ray or as \\>= 10 mm (\\>= 1 cm) with CT scan, MRI, or calipers by clinical exam\n* Patients must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements\n* The effects of talazoparib on the developing human fetus are unknown. For this reason and because PARP inhibitors are known to be teratogenic, women of child-bearing potential must agree to use a highly effective method of contraception for the duration of study participation and for at least 7 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male patients with female partners of reproductive potential and pregnant partners who are treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and for at least 4 months after completion of talazoparib administration\n* Patients must be able to swallow whole tablets or capsules. Nasogastric or gastric-tube (G-tube) administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed\n* Ability to understand and the willingness to sign a written informed consent document\n* Patients must have recurrent, locally advanced or metastatic disease\n* Patients must have progressed on or after at least one line of standard-of-care (SOC) intervention, except for those patients without SOC or for whom talazoparib is SOC\n* PATIENTS WITH OVARIAN CANCER:\n* All patients with ovarian cancer should have one prior platinum-based therapy\n* Patients with ovarian cancer with platinum-sensitive disease are eligible. Patients with platinum-refractory disease are not eligible\n* Patients with gBRCAm ovarian cancer must also have progressed on a PARP inhibitor. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* PATIENTS WITH PANCREATIC CANCER:\n* All patients with pancreatic cancer should have received prior platinum-containing therapy in the metastatic setting\n* PATIENTS WITH BREAST CANCER:\n* Patients with HER2+ breast cancer should have had 2 prior systemic lines of therapy in the metastatic setting, including anti-HER2 therapy\n* Patients with breast cancer who are eligible for a PARP inhibitor by Food and Drug Association (FDA) approvals must have had prior PARP inhibitor as per FDA indication. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* PATIENTS WITH GASTRIC CANCER:\n* Patients with HER2+ gastric cancer should have had received anti-HER2 therapy in the metastatic setting\n* PATIENTS WITH PROSTATE CANCER:\n* Patients with prostate cancer who are eligible for a PARP inhibitor by FDA approvals must have had prior PARP inhibitor for eligibility. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* All patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on prior therapy\n* Patients with castration resistant prostate cancer must have castrate levels of testosterone (\\\u003C 50 ng\u002FdL \\[1.74 nmol\u002FL\\])\n* Patients with metastatic hormone receptor (HR) prostate cancer and mutations in either BRCA1, BRCA2, or ATM should continue to receive anti-androgen receptor (anti-AR) therapy\n\nExclusion Criteria:\n\n* Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter (6 weeks for nitrosoureas or mitomycin C). Patients must be \\>= 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study and be \\>= 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events\n* Patients who have had prior treatment with talazoparib are ineligible\n* Patients who have had prior monoclonal antibody therapy must have completed that therapy \\>= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment) except for monoclonal antibody therapies that have been proven to be safe when combined with PARP inhibitor (PARPi) treatment (such as anti-PD-1\u002FPD-L1 and anti-HER2), which must be completed \\>= 4 weeks prior to enrollment\n* Patients who are receiving any other investigational agents\n* Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for \\>= 1 month without requiring steroid and anti-seizure medication are eligible to participate\n* Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of talazoparib will be determined following review by the principal investigator\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded. Low-dose warfarin (=\\\u003C 1 mg\u002Fday) is permitted\n* Women who are currently lactating\n* History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled",{"count":20,"type":21},[66],"This phase II trial studies if talazoparib works in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and has mutation(s) in deoxyribonucleic acid (DNA) damage response genes who have or have not already been treated with another PARP inhibitor. Talazoparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. All patients who take part on this study must have a gene aberration that changes how their tumors are able to repair DNA. This trial may help scientists learn whether some patients might benefit from taking different PARP inhibitors \"one after the other\" and learn how talazoparib works in treating patients with advanced cancer who have aberration in DNA repair genes.",[27,28,313,210,214,314,30,315,70,316,317,318,31,319,35,320,321,322,323,324,325,77,326,327,328,329,330,331,332,333,334],"Castration-Resistant Prostate Carcinoma","HER2-Positive Breast Carcinoma","Locally Advanced Gastric Carcinoma","Locally Advanced Ovarian Carcinoma","Locally Advanced Pancreatic Carcinoma","Locally Advanced Prostate Carcinoma","Metastatic Gastric Carcinoma","Metastatic Ovarian Carcinoma","Metastatic Pancreatic Carcinoma","Metastatic Prostate Carcinoma","Platinum-Sensitive Ovarian Carcinoma","Recurrent Breast Carcinoma","Recurrent Gastric Carcinoma","Recurrent Pancreatic Carcinoma","Recurrent Prostate Carcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage III Prostate Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","Stage IV Prostate Cancer AJCC v8",{"date":182,"type":47},{"date":337,"type":47},"2021-04-26",{"date":339,"type":21},"2026-12-01",{"name":53,"class":54},{"id":342,"slug":343,"hasResults":12,"nctId":344,"briefTitle":345,"officialTitle":346,"acronym":4,"eligibilityCriteria":347,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":348,"targetDuration":4,"studyType":22,"phases":350,"briefSummary":351,"conditions":352,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":355,"startDateStruct":357,"completionDateStruct":359,"leadSponsor":361,"locationsCount":161},"100544094","phase-1-testing-the-combination-of-the-anticancer-drugs-trastuzumab-deruxtecan-ds-8201a-and-azenosertib-zn-c3-in-patients-with-stomach-or-other-solid-tumors-100544094","NCT06364410","Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors","Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing\u002FAmplified Gastric\u002FGastroesophageal Junction Cancer and Other Solid Tumors","Inclusion Criteria:\n\n* In the dose escalation, patients must have a histologically documented locally advanced, unresectable, or metastatic solid tumor that has progressed following at least one prior line of treatment in the metastatic setting or has no satisfactory alternative treatment option and all of the following:\n\n  * HER2 expression by immunohistochemistry (IHC) (1+, 2+, or 3+) or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS) (on any Clinical Laboratory Improvements Amendments \\[CLIA\\] platform on tissue), AND\n  * T-DXd (DS-8201a)-naive disease\n* In the dose expansion, patients must have histologically documented locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer that has progressed following at least one prior line of treatment in the metastatic setting and have all of the following:\n\n  * HER2 expression by IHC (1+, 2+, or 3+) or HER2 amplification by ISH or NGS (on any CLIA platform on tissue), AND\n  * T-DXd (DS-8201a)-naive disease\n  * Received prior trastuzumab-based treatment, if eligible for such treatment\n* For the dose escalation and dose expansion, patients can have evaluable or measurable disease\n* Potential trial participants should have recovered from clinically significant adverse events (AEs) of their most recent therapy\u002Fintervention prior to enrollment\n* Age ≥ 18 years. Because no dosing or AE data are currently available on the use of T-DXd (DS-8201a) in combination with azenosertib (ZN-c3) in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (Karnofsky ≥ 70%). Both T-DXd (DS-8201a) and azenosertib (ZN-c3) have fatigue as an adverse effect. Due to the overlapping adverse effect, the performance status cannot be less restrictive\n* Absolute neutrophil count ≥ 1.5 × 10\\^9\u002FL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Hemoglobin \\> 9.0 g\u002FdL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Platelets ≥ 100 × 10\\^9\u002FL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Aspartate aminotransferase (AST \\[serum glutamic-oxaloacetic transaminase (SGOT)\\])\u002Falanine aminotransferase (ALT \\[serum glutamate pyruvate transaminase (SGPT)\\]) ≤ 3 × institutional ULN. In the presence of liver metastases, AST or ALT up to 5 × institutional ULN is permitted (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Measured of calculated creatinine clearance (CrCl) ≥ 60 mL\u002Fmin (CrCl should be calculated per institutional standard; glomerular filtration rate can also be used in place of CrCl) ≥ 60 mL\u002Fmin for patients with creatinine levels \\> 1.5 x institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* International normalized ratio\u002Fprothrombin time and activated partial thromboplastin time ≤ 1.5 × institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment\n* Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first cycle of study treatment\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Life expectancy ≥ 3 months\n* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test result within 3 days of study treatment initiation\n* Agents composed of HER2 antibody conjugated to a topoisomerase 1 inhibitor and azenosertib (ZN-c3) are known to be teratogenic; thus, WOCBP must agree to use highly effective contraception from time of screening and throughout the study treatment period and for at least 7 months after final study treatment administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period and for at least 7 months after the final study treatment administration\n* Women of non-childbearing potential defined as premenopausal females with documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for WOCBP if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their postmenopausal status, they can resume use of HRT during the study without use of a contraception method\n* Male patients involved with WOCBP must agree to use a highly effective form of contraception or avoid intercourse from time of screening and throughout the study treatment period and for at least 4 months after the last dose of study treatment. Male patients must not freeze or donate sperm starting at screening and throughout the study period and at least 4 months after the final study treatment administration. Preservation of sperm should be considered prior to enrollment in this study\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n* Willing to undergo biopsy as required by the study (dose expansion only)\n\n  * Note: Patients in the dose escalation who have insufficient\u002Finadequate archival tissue may have optional pre-treatment biopsy\n* Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery (any surgical incision should be fully healed prior to study drug administration); 4 weeks from antibody-based therapy; 2 weeks or or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); and 4 weeks from radiation therapy. These washout periods are included to ensure patients have maximal bone marrow recovery and as this is a multicenter trial, to ensure uniformity in interpretation of recovery\n\nExclusion Criteria:\n\n* As azenosertib (ZN-c3) is a substrate of CYP3A4, use of prescription or non-prescription drugs known to be moderate or strong inhibitors or inducers of CYP3A4 are prohibited with the exception of moderate or strong inhibitors or inducers of CYP3A4 that are part of the prophylactic antiemetic regimen. Chloroquine\u002Fhydroxychloroquine are metabolized by CYP3A4 and therefore, should be prohibited. For patients who have received prior moderate or strong inhibitors or inducers of CYP3A4, the required washout period is approximately 5 half-lives prior to study treatment initiation\n* Patients who are receiving any other investigational agents\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs\n* Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy\n* Patients who require supplemental oxygen for activities of daily living\n* Pregnant women are excluded from this study because T-DXd (DS-8201a) and azenosertib (ZN-c3) have the potential risk for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with T-DXd (DS-8201a) and azenosertib (ZN-c3), breastfeeding should be discontinued if the mother is treated with T-DXd (DS-8201a) or azenosertib (ZN-c3)\n* Patients with history of non-infectious pneumonitis\u002Finterstitial lung disease (ILD), current ILD, or where suspected ILD cannot be ruled out by imaging at screening\n* Patients with active infections requiring treatment (antibiotic, antifungal, or antiviral) at the time of study treatment initiation are not eligible. Patients who have completed such treatment and whose infection is controlled\u002Fresolved (and afebrile) for at least 7 days before cycle 1 day 1 are eligible\n* Patients with history of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills\n* Patients with current signs or symptoms of bowel obstruction including sub-occlusive disease related to underlying disease\n* Patients with a medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association class IIb to IV), and\u002For troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment\n* Patients with clinically significant corneal disease\n* Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment)\n* Patients with history of Torsades de Pointes unless all risk factors that contributed to Torsades de Pointes have been corrected\n* Based on an average of triplicate 12-lead electrocardiogram (ECG), patients with a mean resting corrected QT (QTc) interval using Fridericia formula of \\> 470 msec for both males and females at screening or a history of congenital long QT syndrome will be excluded\n* Patients with prior treatment with a WEE1 inhibitor (dose escalation and dose expansion)\n* Patients with prior treatment with T-DXd (DS-8201a) or other topoisomerase inhibitors (dose escalation and dose expansion)\n* Patients with uncontrolled intercurrent illness\n* Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation\n* Patients with clinically significant chronic gastrointestinal disorder with diarrhea as a major symptom; ≥ grade 2 diarrhea at baseline. Please contact the protocol principal investigator (PI) for any patient with more than two episodes of diarrhea per day averaged over at least a 7-day period at time of screening to determine whether the diarrhea would be considered clinically significant\n* Patients with spinal cord compression",{"count":349,"type":21},48,[24],"This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), that have spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and\u002For more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.",[210,211,214,215,315,224,70,319,242,35,353,280,41],"Unresectable Gastric Carcinoma","2026-06-16",{"date":356,"type":47},"2026-06-17",{"date":358,"type":47},"2025-02-03",{"date":360,"type":21},"2027-07-08",{"name":53,"class":54},{"id":363,"slug":364,"hasResults":12,"nctId":365,"briefTitle":366,"officialTitle":367,"acronym":4,"eligibilityCriteria":368,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":369,"targetDuration":4,"studyType":22,"phases":371,"briefSummary":372,"conditions":373,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":374,"startDateStruct":375,"completionDateStruct":377,"leadSponsor":378,"locationsCount":379},"100540005","phase-2-personalized-antibody-drug-conjugate-therapy-based-on-rna-and-protein-testing-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-adc-match-screening-and-treatment-trial-100540005","NCT06311214","Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)","Optimizing Antibody-Drug Conjugate Therapy Through Molecular Analysis for Therapy Choice (ADC MATCH)","Inclusion Criteria:\n\n* SCREENING PROTOCOL INCLUSION CRITERIA:\n* Patients must have histologically confirmed solid tumor requiring therapy and meet one of the following criteria:\n\n  * Patients must have disease not amenable to curative-intent therapy AND\n  * Patients who have had disease progression after treatment with all available therapies for their disease that are known to confer benefit or are intolerant to such treatment will be eligible, if other eligibility criteria are met. If the patient is currently receiving therapy without progression, the clinician must have assessed that the current therapy is no longer benefitting the patient, or that the patient is not tolerating the therapy. Patients can be screened on ADC MATCH if they have had three or fewer-lines of chemotherapy in the advanced\u002Fmetastatic setting and are expected to need a treatment change within 6 months, and ADC MATCH is felt to be appropriate next line therapy AND\n  * Patients with disease for which no standard treatment exists that has been shown to confer benefit OR\n  * Patients who are willing to forego standard therapies known to confer benefit\n\n    * NOTE: Patients can be on therapy at the time of initiating the Screening Protocol if the patient is interested in treatment on ADC MATCH upon progression, and the physician deems this appropriate\n* Patient must have undergone RNA testing in a Clinical Laboratory Improvement Act (CLIA) environment or must submit archival tissue to determine RNA overexpression of ADC TOIs by the TARGET Assay. Patients who have high TOI RNA expression will have confirmation of TOI expression by CLIA IHC assay at MD Anderson Cancer Center (MDACC). Only patients with confirmed TOI protein expression will be eligible for assignment to a treatment cohort. Retrospective confirmation in another central laboratory may also be performed. (A proportion of specimens in patients who are negative for RNA overexpression may be tested to better understand the concordance between the TARGET Assay and immunohistochemistry (IHC) assays, as funding and tissue availability allows. Only patients with RNA and protein expression with be eligible for treatment on ADC MATCH)\n* Patients must be willing to undergo mandatory pre-treatment and on-treatment tumor biopsies. Patients who do not consent to these research biopsies will not be eligible for prescreening. Patients who have screened and consented to a treatment cohort but are found to have disease that cannot be safely biopsied will be eligible for treatment provided all other eligibility criteria are met\n* Patients must have measurable disease. (Per radiologic imaging within the past 2 months).\n\n  * Note: Patients with active metastatic disease that is not measurable but who are expected to be eligible for a Treatment Cohort can be screened after discussion with the primary investigator (PI)\n* Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of the Cancer Therapy Evaluation Program (CTEP) investigational new drug (IND) agents to be used in the study in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group performance status of 0-2 based on most recent assessment (Karnofsky ≥ 50%)\n* No history of transfusion dependence\n* No history of persistent bone marrow suppression (absolute neutrophil count ≥ 1,500\u002FmL and platelets ≥ 100,000\u002FmL not attributable to active therapy; patients currently on bone marrow suppressive therapy can undergo assessment for the screening protocol but cannot be treated on any of the treatment cohorts unless bone marrow suppression is reversed off the suppressive therapy) (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)\n* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × ULN (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)\n* Aspartate transaminase (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine transaminase (serum glutamate pyruvate transaminase \\[SGPT\\]) ≤ 2.5 × institutional ULN. Transaminases up to 5 × ULN in the presence of liver metastases are not allowed to initiate the screening protocol but are allowed for the treatment cohorts (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)\n* Creatinine ≤ institutional ULN OR glomerular filtration rate ≥ 60 mL\u002Fmin\u002F1.73 m\\^2 for patients with creatinine levels above institutional normal unless data exists supporting safe use at lower kidney function values, no lower than 30 mL\u002Fmin\u002F1.73 m\\^2 (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)\n* Patients must have albumin ≥ 3 g\u002FdL\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational agents are eligible for this study\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this study, patients should be class 2B or better\n* Women of childbearing potential must not be known to be pregnant. Pregnancy testing is not required\n* Ability to understand and the willingness to sign a written informed consent document\n* ADDITIONAL INCLUSION CRITERIA FOR TREATMENT COHORTS:\n* Women of childbearing potential must have a negative serum pregnancy test result at treatment cohort screening\n* The effects of the study drugs on the developing human fetus are unknown. For this reason and because investigational agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completion of study drug administration (unless otherwise indicated in the eligibility section \\[Section 2\\] of the Treatment Cohort protocols). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after completion of study drug administration\n* Hemoglobin \\> 9.0 g\u002FdL\n* Leukocytes ≥ 3000\u002FmL\n* Absolute neutrophil count ≥ 1,500\u002FmL\n* Platelets ≥ 100,000\u002FmL\n* Patient must be willing to sign the relevant treatment cohort consent form\n* Patients should have received no more than 3 prior lines of chemotherapy in the advanced\u002Fmetastatic setting. Therapy given for only 1 cycle and discontinued because of toxicity in the absence of disease progression will not be counted as a line of therapy. Radio-sensitizing chemotherapy, if only given with radiation therapy will not be considered a line of therapy\n* Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* COHORT A INCLUSION CRITERIA:\n* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort A registration\n* Patient must have high Trop-2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay\n\n  * Patients who have Trop-2 IHC testing without RNA testing or who have Trop-2 IHC 2 or 3+ expression but do not have Trop-2 expression detected on RNA testing will not be eligible for the trial.\n  * Patients who have Trop-2 RNA expression and Trop-2 IHC 2+ or 3+ on another Trop-2 IHC test will undergo Trop-2 testing with the integral MDACC IHC assay\n  * Patients who already have RNA expression testing demonstrating Trop-2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision Oncology Decision Support team without having to repeat Trop-2 IHC results as part of pre-screening. Patients who have had TROP2 2+ testing result performed outside of MDACC will have to undergo MDACC TROP2 IHC analysis before enrollment\n* COHORT B INCLUSION CRITERIA:\n* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort B registration\n* Patient must have high Nectin-4 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay\n* COHORT C INCLUSION CRITERIA:\n* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort C registration\n* Patient must have HER2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center (MDACC) IHC assay\n\n  * Patients who have HER2 IHC testing without RNA testing or who have HER2 IHC 2 or 3+ expression but do not have HER2 expression detected on RNA testing will not be eligible for the trial\n  * Patients who have HER2 RNA expression and HER2 IHC 3+ or 2+ on another HER2 IHC test will undergo HER2 testing with the integral MDACC IHC assay\n  * Patients who already have RNA expression testing demonstrating HER2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision Oncology Decision Support team without having to repeat HER2 IHC results as part of pre-screening. Patients who have had HER2 2+ testing result performed outside of MDACC will have to undergo MDACC HER2 IHC analysis before enrollment\n* Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after completion of study drug administration. Women should not breastfeed during the study treatment period and for 7 months after completion of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of study drug administration. Female patients must not donate, or retrieve for their own use, ova from the time of screening throughout the study treatment period and for at least 7 months after the final study drug administration. Female patients may wish to consider preservation of ova prior to enrollment in the study. Male patients should refrain from freezing or donating sperm during the study and for 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in the study\n* LVEF ≥50% within 28 days before enrollment\n\nExclusion Criteria:\n\n* SCREENING PROTOCOL EXCLUSION CRITERIA:\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease. Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks after central nervous system-directed therapy shows no evidence of progression\n* Clinically significant cardiovascular condition including: (1) history of congestive heart failure (New York Health Association class \\> 2), (2) any history of unstable angina, (3) myocardial infraction within the past 12 months, or (4) any history of supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention within the past 12 months\n* History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful\n* Active or chronic corneal disorder including, but not limited to, Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and\u002For active ocular conditions requiring ongoing treatment\u002Fmonitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the ADCs used in the study\n* History of interstitial lung disease or pneumonitis requiring steroid therapy\n* Grade 2 or greater peripheral neuropathy\n* Patients requiring the use of full dose coumarin-derivative anticoagulants such as warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted\n\n  * Note: Warfarin may not be started while enrolled in the treatment cohorts. Stopping the anticoagulation for biopsy should be per site standard operating practice\n* Pregnant women are excluded from the study because the study drugs are investigational or approved agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with any of the study drugs, breastfeeding should be discontinued if the mother is treated with any of the study drug\n* ADDITIONAL EXCLUSION CRITERIA FOR TREATMENT COHORTS:\n* Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery; 4 weeks from antibody-based therapy; 2 weeks or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); and 4 weeks from radiation therapy. Patients should have received no more than 3 prior lines of chemotherapy. Testosterone suppression as supportive treatment for castration-resistant prostate cancer and ovarian suppression in premenopausal patients with breast cancer that have supportive treatment and not anticancer treatment role (with luteinizing hormone-releasing hormone analogs) will be allowed if the patients were on these supportive treatments before starting the study. Use of bone-modifying medications (bisphosphonates or denosumab) will be allowed. Palliative radiotherapy of non-target lesions is permitted, but presence of new or worsening metastases will be considered progressive disease. If there is clear evidence of clinical benefit, study treatment may be continued 2 weeks after completion of palliative radiotherapy to lesions that are non-target lesions. Patients can be on therapy during treatment cohort screening\n* Patients who are currently receiving any other investigational agent(s)\n* Received systemic therapy with corticosteroids at \\> 20 mg\u002Fday prednisone or equivalent within 1 week prior to cycle 1 day 1\n* Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia\n* When the corrected QT interval (QTc) by Fridericia's formula is \\\u003C 120 ms, \\> 450 ms in males and \\> 470 ms in females. When the QTc by Rautaharju's formula is ≥ 120 ms, \\> 450 ms in males and \\> 470 ms in females\n* Uncontrolled infection requiring intravenous antibiotic, antiviral, or antifungal use\n* Received a live, attenuated vaccine within 30 days prior to cycle 1 day 1. Enrolled patients should not receive live vaccine during the study. Non-live COVID vaccines will be allowed on study, but it is recommended to avoid their use during the first treatment cycle (from 3 days prior to cycle 1 day 1 through cycle 2 day 3)\n* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations\n* COHORT A EXCLUSION CRITERIA:\n* Patients with histologically documented advanced colorectal cancer, urothelial cancer, head and neck cancer (Note: exceptions include patients with adenoid cystic cancer, salivary gland cancer, thyroid cancer, and parathyroid cancer, who are eligible), triple negative breast cancer (TNBC), HR-positive breast cancer, HER2-positive breast cancer, small cell lung cancer, NSCLC, and endometrial cancer\n\n  * Note: Patients with cancer of unknown primary are allowed\n* Patients who have received growth factor support within 2 weeks of study treatment initiation\n* Coadministration of sacituzumab govitecan-hziy(IMMU-132) with inhibitors of UGT1A1 may increase systemic exposure to the active metabolite, SN-38. UGT1A1 inhibitors should not be administered concomitantly with sacituzumab govitecan-hziy (IMMU-132) unless there are no therapeutic alternatives\n* Prior topoisomerase 1 inhibitor treatment\n* Prior treatment with a Trop-2-targeting ADC\n* Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of treatment cohort A registration\n* COHORT B EXCLUSION CRITERIA:\n* Patients with histologically documented advanced urothelial cancer, head and neck cancer (to include salivary gland cancer and adenoid cystic cancer), breast cancer, lung cancer, gastric cancer, gastroesophageal junction cancer, esophageal cancer, prostate cancer, or penile cancer\n\n  * Note: Patients with cancer of unknown primary are allowed\n* Concomitant use of strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4. Washout period is 2 weeks prior to study treatment initiation\n* History of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes mellitus is defined as hemoglobin A1c ≥ 8% or hemoglobin A1c between 7 and \\\u003C 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained\n* Known active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated\n* Known hypersensitivity to enfortumab vedotin or to any excipient in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20), or known hypersensitivity to biopharmaceutical produced in Chinese hamster ovary cells\n* Prior treatment with an ADC with vedotin payload\n* COHORT C EXCLUSION CRITERIA:\n* Patients with histologically documented advanced breast cancer, non-small cell lung cancer (NSCLC), colorectal carcinoma (CRC), gastric cancer, or gastroesophageal junction (GEJ) cancer\n\n  * Note: Patients with cancer of unknown primary are allowed\n* Previous treatment with topoisomerase I inhibitors as a free form or as other formulations\n* Prior",{"count":370,"type":21},500,[66],"This phase II ADC MATCH screening and multi-sub-study treatment trial is evaluating whether biomarker-directed treatment with one of three antibody-drug conjugates (ADCs) (sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan) works in treating patients with solid tumor cancers that have high expression of the Trop-2, nectin-4, or HER2 proteins and that may have spread from where they first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced) or to other places in the body (metastatic). Precision medicine is a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, or treat disease in a way that is tailored to the patient. ADCs such as sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan are monoclonal antibodies attached to biologically active drugs and are a form of targeted therapy. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a drug called govitecan. Sacituzumab attaches to a protein called Trop-2 on the surface of tumor cells and delivers govitecan to kill them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. Trastuzumab deruxtecan is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Personalized treatment with sacituzumab govitecan, enfortumab vedotin, or trastuzumab deruxtecan may be an effective treatment option for patients with advanced or metastatic solid tumors that screen positive for high expression of Trop-2, nectin-4, or HER2, respectively.",[69,35],{"date":356,"type":47},{"date":376,"type":47},"2025-03-18",{"date":299,"type":21},{"name":53,"class":54},27,{"id":381,"slug":382,"hasResults":12,"nctId":383,"briefTitle":384,"officialTitle":385,"acronym":4,"eligibilityCriteria":386,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":387,"targetDuration":4,"studyType":388,"phases":4,"briefSummary":389,"conditions":390,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":393,"startDateStruct":394,"completionDateStruct":396,"leadSponsor":398,"locationsCount":161},"100521894","evaluation-of-anti-pd-1-therapy-by-monitoring-t-cell-responses-in-melanoma-lung-and-other-cancer-types-100521894","NCT06075524","Evaluation of Anti-PD-1 Therapy by Monitoring T Cell Responses in Melanoma, Lung and Other Cancer Types","Maximizing Anti-PD-1 Therapy by Monitoring T Cell Responses in Melanoma, Lung and Other Cancer Types","Inclusion Criteria:\n\n* Are 18 years of age or older\n* Have histologic evidence of locally or regionally advanced or stage IV malignancy\n* Are considered appropriate for starting therapy with anti-PD-1\u002Fanti-PD-L1 monoclonal antibody by their treating physician (prior therapy with immune checkpoint inhibitor (ICI) is allowed)\n* Have an understanding of the protocol and its requirements, risks, and discomforts\n* Are willing to undergo peripheral blood collection at the time points mentioned in the protocol\n* Are able and willing to sign an informed consent\n\nExclusion Criteria:\n\n* Inability on the part of the patient to understand the informed consent or be compliant with the protocol\n* Patients receiving any concurrent anti-cancer therapy or investigational agents (with the exception of an anti-PD-1\u002Fanti-PD-L1 agent as mentioned above)\n* Patients who are pregnant, nursing, or are of childbearing potential and are unwilling to employ adequate contraception",{"count":370,"type":21},"OBSERVATIONAL","This study explores the role of T cells in monitoring disease status and response during anti-PD-1\u002FPD-L1 treatment in patients with melanoma, lung and other cancer types. Measuring levels of specific targets such as Bim and soluble PD-L1 during therapy may help track treatment resistance and clinical outcomes. This information may also help researchers determine why some people with melanoma, lung and other cancer types respond to PD-1\u002FPD-L1 treatment and others do not.",[209,213,391,70,228,392,35,178,251,180],"Locally Advanced Lung Carcinoma","Metastatic Lung Carcinoma",{"date":294,"type":47},{"date":395,"type":47},"2015-06-15",{"date":397,"type":21},"2028-12-31",{"name":301,"class":140},{"id":400,"slug":401,"hasResults":12,"nctId":402,"briefTitle":403,"officialTitle":404,"acronym":4,"eligibilityCriteria":405,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":406,"targetDuration":4,"studyType":22,"phases":408,"briefSummary":409,"conditions":410,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":411,"startDateStruct":412,"completionDateStruct":414,"leadSponsor":416,"locationsCount":417},"100492053","phase-1-testing-the-combination-of-two-anti-cancer-drugs-peposertib-m3814-and-tuvusertib-m1774-for-advanced-solid-tumors-100492053","NCT05687136","Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and Tuvusertib (M1774) for Advanced Solid Tumors","A Molecularly Driven Phase 1b Dose Escalation and Dose Expansion Study of the DNA-PK Inhibitor Peposertib (M3814) in Combination With the ATR Inhibitor Tuvusertib (M1774)","Inclusion Criteria:\n\n* Patients must have histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or if the treating investigator deems the study appropriate.\n* For the dose escalation and dose expansion phases, patients must have genomic (tumor next-generation sequencing \\[NGS\\], circulating tumor deoxyribonucleic acid \\[ctDNA\\], fluorescence in situ hybridization \\[FISH\\], etc.) or immunohistochemical evidence (e.g., loss of expression) of inactivating ATM mutations, MYC amplification, mutation of FBXW7, CCNE1 amplification, SWI\u002FSNF member mutation (ARID1A, PBRM1, SMARCA4, ARID2, ARID1b, SMARCB1, SMARCA2, SS18) and mutation or loss of expression of ATRX\u002FDAXX. Mutations may be germline or somatic. All mutations\u002Falterations must be approved by the overall principal investigator (PI). Other SWI\u002FSNF mutations may be considered after discussion with the overall PI.\n* Progression on at least one prior standard therapy (if no standard therapy exists, the patient may be allowed if the treating investigator deems appropriate).\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with tuvusertib (M1774) in patients \\\u003C 18 years of age, children are excluded from this study.\n* Life expectancy \\> 3 months.\n* Eastern cooperative oncology group (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%).\n* Measurable disease by response evaluation criteria in solid tumors (RECIST) 1.1 (RECIST 1.1 non-measurable disease permitted for the dose escalation portion).\n* Hemoglobin \\>= 9 g\u002FdL.\n* Absolute neutrophil count \\>= 1,500\u002FmcL.\n* Platelets \\>= 100,000\u002FmcL.\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN).\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 3 × institutional ULN or =\\\u003C 5.0X the ULN if liver metastases are present.\n* Glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin\u002F1.73m\\^2.\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Anti-retroviral therapy agents must be considered for potential drug-drug interactions per exclusion.\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured or have evidence of clearance of HCV (i.e., undetectable HCV viral load). For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.\n* Able to swallow whole capsules or tablets.\n* Willing to undergo paired biopsies (expansion arm); if a biopsy is not feasible or safe, the patient may be allowed to participate after discussion with the overall PI.\n* Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n\n  * Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 6 months after the last dose of study medication.\n  * Male patients of reproductive potential must agree to avoid impregnating a partner while receiving study drug and for 3 months after the last dose of study drug by complying with adequate methods of contraception.\n  * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and\u002For family member available will also be eligible.\n\nExclusion Criteria:\n\n* Patients who have received immunotherapy within 21 days of Cycle 1 Day 1.\n* Patients who have received therapeutic radiation therapy within 21 days, or palliative radiation therapy within 7 days, of Cycle 1 Day 1.\n* Patients who have undergone major surgery within 21 days of Cycle 1 Day 1.\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> Grade 1) with the exception of alopecia, controlled endocrine toxicity (e.g., hypothyroidism), and cutaneous toxicity which will be permitted at Grade 2.\n* Patients who are receiving any other investigational agents.\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required during the first cycle of therapy.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to peposertib (M3814) and tuvusertib (M1774).\n* Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes, CYP1A2, CYP3A4\u002F5, CYP2C19, and CYP2C9. Concomitant use of substrates hMATE1, hMATE2, and CYP3A4\u002F5 substrates with a narrow therapeutic index are also excluded. Opioids may interact with these enzymes; use of opioids while on study is allowed but should be closely monitored. Concomitant administration of sensitive substrates of P-gp, BCRP, OCT1, OATP1B1, and OATP1B3 should be avoided (if the use is unavoidable, carefully monitor patients for signs of increased toxicity). Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time before the patient can be treated:\n\n  * Strong inducers of CYP1A2, CYP3A4\u002F5, CYP2C19, and CYP2C9: \\>= 3 weeks prior to study treatment.\n  * Strong inhibitors of CYP1A2, CYP3A4\u002F5, CYP2C19, and CYP2C9: \\>= 1 week prior to study treatment.\n  * Substrates of hMATE1, hMATE2, CYP3A4\u002F5, P-gp, BCRP, OCT1, OATP1B1, and OATP1B3 with a narrow therapeutic index: \\>= 1 day prior to study treatment.\n* Patients who cannot discontinue proton-pump inhibitors (PPIs). H-2-receptor antagonist should be held during the 2 weeks of concurrent dosing with peposertib (M3814). There is no H-2-receptor antagonist restriction during the off weeks without peposertib (M3814) dosing. H-2-receptor antagonists should not be taken within 12 hours before or 2 hours after tuvusertib (M1774). Antacids should not be taken within 2 hours before or 2 hours after tuvusertib (M1774).\n* Patients who received hematopoietic growth factor (e.g., granulocyte colony-stimulating factor, erythropoietin) within 14 days prior to the first dose of study intervention.\n* Patients with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.\n* QTcF (using the Fridericia correction calculation) of \\>= 470 msec\n* Pregnant women and women who are breastfeeding are excluded from this study because the effects of the study drugs on the developing fetus are unknown.\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as assessed by the treating investigator may be included with the approval of the sponsor-investigator.",{"count":407,"type":21},66,[24],"This phase I trial tests the safety, side effects and best dose of peposertib (M3814) in combination with tuvusertib (M1774) in treating patients with solid tumors that have spread to other places in the body (advanced). Peposertib and tuvusertib stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.",[69,35,41],{"date":356,"type":47},{"date":413,"type":47},"2024-06-07",{"date":415,"type":21},"2026-08-31",{"name":53,"class":54},6,{"id":419,"slug":420,"hasResults":12,"nctId":421,"briefTitle":422,"officialTitle":423,"acronym":4,"eligibilityCriteria":424,"healthyVolunteers":12,"sex":17,"minAge":425,"maxAge":4,"enrollmentInfo":426,"targetDuration":4,"studyType":22,"phases":428,"briefSummary":429,"conditions":430,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":433,"startDateStruct":434,"completionDateStruct":436,"leadSponsor":438,"locationsCount":439},"100467889","phase-1-testing-the-safety-and-efficacy-of-the-combination-of-two-anti-cancer-drugs-zen003694-and-abemaciclib-for-adult-and-pediatric-patients-12-17-years-with-metastatic-or-unresectable-nut-carcinoma-breast-cancer-and-other-solid-tumors-100467889","NCT05372640","Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors","A Phase 1 Study of BET Bromodomain Inhibitor ZEN003694 in Combination With the CDK4\u002F6 Inhibitor Abemaciclib in Patients With NUT Carcinoma, Breast Cancer and Other Solid Tumors","Inclusion Criteria:\n\n* Participants must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* Dose Escalation Cohort Only: Participants must have evaluable disease or measurable disease per RECIST 1.1 criteria\n* Dose Expansion Cohort Only:\n\n  * Participants must have a diagnosis of NUT carcinoma (NC) based on standard criteria for the disease, with diagnostic testing performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory:\n\n    * Ectopic expression of NUT protein per World Health Organization (WHO) criteria as determined by immunohistochemistry (IHC) testing, OR\n    * Detection of the NUT gene translocation as determined by fluorescence in situ hybridization (FISH) testing, OR\n    * Detection of the NUT gene translocation as determined by either deoxyribonucleic acid (DNA) next-generation sequencing (NGS) or ribonucleic acid (RNA) sequencing.\n  * Participants must have measurable disease per RECIST 1.1 criteria\n* Any number of prior lines of therapy in the metastatic setting are allowed, including prior BET inhibitor therapy and prior CDK4\u002F6 inhibitor therapy\n* Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \\[CTCAE\\] grade =\\\u003C 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy\n* Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy\n* Participants may have previously undergone surgical resection\n* Age \\>= 12 years. Patients 12-17 years of age must be \\> 40 kg at enrollment. Patients 12-17 years of age will not participate in the mandatory tumor biopsies. Since there is no data on patients less than 18 years of age, this population may require lower doses and additional safety precautions and should be closely monitored. Because no dosing or adverse event data are currently available on the use of ZEN003694 in combination with abemaciclib in patients \\\u003C 12 years of age, younger children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 for participants \\>= 16 years of age, Lansky \\>= 50% if \\\u003C 16 years of age\n* Hemoglobin \\>= 8 g\u002FdL; Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion\n* Absolute neutrophil count \\>= 1.5 x 10\\^9\u002FL\n* Platelets \\>= 1 x 10\\^11\u002FL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) for age. Patients with Gilbert's syndrome with a total bilirubin =\\\u003C 2.0 times ULN and direct bilirubin within normal limits are permitted\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional ULN for age\n* Serum or plasma creatinine =\\\u003C 1.5 x institutional ULN OR calculated creatinine clearance \\>= 50 mL\u002Fmin (via the chronic kidney disease epidemiology \\[CKD-EPI\\] glomerular filtration rate estimation) for participants \\>= 18 years old, or 60 mL\u002Fmin\u002F1.73m\\^2 for patients 12-17 years as calculated based on bedside Schwartz formula\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Hepatitis C (HepC antibody) testing is required. Hepatitis C RNA is optional; however, a confirmatory negative Hepatitis C RNA test must be obtained to be able to enroll participants with positive Hepatitis C antibody due to prior resolved disease\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and has been clinically stable for at least 1 month. Patients must meet the following criteria:\n\n  * Disease outside the CNS is present\n  * Recovery from acute toxicity associated with the treatment to =\\\u003C CTCAE grade 1 or baseline (with the exception of alopecia), with no requirement for escalating doses of corticosteroids over the past 7 days\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* Ability to swallow and retain oral medications\n* The effects of ZEN00364 and abemaciclib on the developing human fetus are unknown. For this reason and because BETi and CDKi-inhibiting agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential must have a negative pregnancy test prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 weeks after completion of ZEN003694 and abemaciclib administration\n\n  * For female subjects of child-bearing potentially receiving ZEN003694, hormonal means of birth control alone, such as oral, injectable, dermal, subdermal or topical contraceptives are NOT acceptable forms of birth control given that their efficacy has not been evaluated when given in combination with the investigational drugs. \"Adequate contraception\" is defined as the following:\n\n    * Contraceptive methods with a failure rate of =\\\u003C 1% used in combination with the barrier method. The following contraceptive methods are acceptable to use in combination with the barrier method: intrauterine device (IUD), intrauterine system (IUS), or oral contraceptive pills (OCPs) that meet the \\\u003C 1% failure rate as stated in the product label. Note: Hormonal IUDs\u002FOCPs may only be used if the following criteria are met: male condoms are required AND subjects are informed of the potential for reduced systemic hormone levels from the IUD\u002FOCP when taking ZEN003694. Alternatively, male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, \"documented\" refers to the outcome of the investigator's\u002Fdesignee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\n  * Male subjects with female partners of child-bearing potential must use one of the following contraceptive methods:\n\n    * Vasectomy with documentation of azoospermia OR\n    * Condom use PLUS partner use of a highly effective contraceptive (=\\\u003C 1% rate of failure per year) such as intrauterine device or system, or hormonal birth control such as contraceptive subdermal implant, combined estrogen and progestogen oral contraceptive, injectable progestogen, contraceptive vaginal ring, or percutaneous contraceptive patches\n  * Male subjects should not donate sperm while on study and for 12 weeks after the last dose of study medication. Male subjects whose partners are or become pregnant must continue to use condoms for 12 weeks after the last dose of study medication\n* Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and\u002For family member available may be eligible after discussion with the Principal Investigator of this study. There will be a separate assent process for minors\n\nExclusion Criteria:\n\n* Participants who have had cytotoxic chemotherapy, immunotherapy, or other investigational therapy within 2 weeks prior to entering the study. There is a two-week required washout period for previous BET inhibitor therapy\n* Participants who have had radiotherapy within at least 2 weeks prior to entering the study. Stereotactic radiosurgery (SRS) within 1 week prior to entering the study will be allowed\n* Participants who have had major surgery within 3 weeks prior to entering the study\n* Participants who have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 1 week (whichever is shorter) of study entry\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or abemaciclib\n* Patients requiring medications or substances that are strong inhibitors or strong inducers of CYP3A4 or CYP3A enzymes are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 and abemaciclib. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http:\u002F\u002Fmedicine.iupui.edu\u002Fclinpharm\u002Fddis\u002Ftable.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients with uncontrolled intercurrent illness, including but not limited to: ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (e.g. estimated creatinine clearance \\\u003C 30ml\u002Fmin), history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea that, in the judgment of the investigator, would preclude participation in this study\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. As proton pump inhibitors (PPIs), H2 receptor antagonists, and antacids may alter the pharmacokinetics of ZEN003694 by reducing ZEN003694 exposure, patients receiving proton pump inhibitors are ineligible. If H2 blockers or other acid reducing agents are used concomitantly with ZEN003694, a staggered dosing schedule should be used. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Pregnant women are excluded from this study because ZEN003694 is a BETi agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694, breastfeeding should be discontinued if the mother is treated with ZEN003694. These potential risks may also apply to other agents used in this study\n* Fridericia's formula-corrected QT interval (QTcF) \\>= 450 msec on screening electrocardiogram (ECG) by Fredericia (machine or manual read allowed). Patients should avoid medications which prolong the QT\n* Patients receiving any medications or substances that are Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) or Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Patients with radiation to \\> 25% of the bone marrow\n* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694\n* Myocardial infarction or unstable angina within 6 months prior to the first dose of ZEN003694\n* Impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 and\u002For abemaciclib\n* The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest","12 Years",{"count":427,"type":21},45,[24],"This phase I trial tests the safety, side effects, and best dose of ZEN003694 when given together with abemaciclib in treating patients with NUT carcinoma, breast cancer or other solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that overproduce BET protein. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ZEN003694 and abemaciclib may help shrink or stabilize cancer in patients with NUT carcinoma, breast cancer or other solid tumors.",[27,28,31,35,431,37,41,432],"Metastatic NUT Carcinoma","Unresectable NUT Carcinoma",{"date":356,"type":47},{"date":435,"type":47},"2023-08-10",{"date":437,"type":21},"2027-06-07",{"name":53,"class":54},7,{"id":441,"slug":442,"hasResults":12,"nctId":443,"briefTitle":444,"officialTitle":445,"acronym":4,"eligibilityCriteria":446,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":447,"targetDuration":4,"studyType":22,"phases":449,"briefSummary":450,"conditions":451,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":452,"startDateStruct":453,"completionDateStruct":455,"leadSponsor":457,"locationsCount":20},"100464385","phase-2-testing-the-combination-of-the-anti-cancer-drugs-zen003694-zen-3694-and-talazoparib-in-patients-with-advanced-solid-tumors-the-combet-trial-100464385","NCT05327010","Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial","Phase 2 Trial of the Combination of the BET Inhibitor, ZEN003694 (ZEN-3694), and the PARP Inhibitor Talazoparib, in Patients With Molecularly-Selected Solid Tumors (ComBET)","Inclusion Criteria:\n\n* Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* Patients must have a tumor lesion that can be biopsied with 'low' or 'minimal' risk and at least one measurable disease site, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1\n\n  * Note: Tumor lesions that are situated in a previously irradiated area may or may not be considered measurable\n* Patients in cohorts 1, 2, and 4 should have at least one relevant mutation. Patients enrolled in cohorts 1-3 do not require that PARP inhibitor (i) be the immediate prior therapy to be eligible for the trial. Patients should sign a screening consent that will allow the review of local next generation sequencing (NGS) or equivalent Clinical Laboratory Improvement Amendment (CLIA)-certified assay results by MD Anderson's Precision Oncology Decision Support (PODS) team to ensure that the mutations are actionable. No variants of uncertain significance (VUS) will be allowed\n\n  * Patients in Cohort 1 must have (i) a germline or somatic mutation in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination-therapy\n  * Patients in Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: BARD1; FANCA; BRIP1; PALB2; RAD51; RAD51C; RAD51D, with no evidence of mutations in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination therapy\n  * Patients in Cohort 3 must be (i) patients who have had PR\u002FCR on prior PARPi monotherapy or PARPi combination treatment; and (ii) patients with no evidence of BRCA1 or BRCA2 mutations or any of the relevant DDR aberrations listed in cohort 2. Patients with ovarian cancer should not have progressed on platinum-therapy within six months of therapy\n  * Patients in Cohort 4 must have KRAS mutated advanced solid tumors. Prior treatments with KRAS inhibitors are permitted. Patients with KRAS G12C mutations must have already had KRAS G12C targeted therapy (e.g., sotorasib) previously\n* Patients must have received at least one line of systemic therapy in the advanced\u002Fmetastatic setting. Subjects with diseases without known effective options, and subjects who have declined standard of care therapy prior to study introduction, are also eligible. Patients with ovarian cancer in cohort 3 should not have progressed on platinum within six months of therapy\n* Age \\>= 18 years\n\n  * Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with talazoparib in patients \\\u003C 18 years of age, children are excluded from this study\n* Patients must be greater than 4 weeks (6 weeks for nitrosoureas or mitomycin C) beyond treatment with any chemotherapy or other investigational therapy including hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation. Patients must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities =\\\u003C grade 1) with the exception of alopecia or anorexia\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%)\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Platelets \\>= 150,000\u002FmcL\n* Hemoglobin \\>= 10.0 g\u002FdL (no blood transfusions in the preceding 28 days)\n* Total bilirubin 1.5 x =\\\u003C institutional upper limit of normal (ULN) OR direct bilirubin = ULN for subjects with total bilirubin levels \\> 1.5 x ULN\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional ULN\n* Creatinine 1.5 x institutional ULN OR glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin\u002F1.73 m\\^2 for subjects with creatinine levels \\> 1.5 x institutional ULN, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL\u002Fmin\u002F1.73 m\\^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable viral load while on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable. Patients with known symptomatic brain metastases requiring steroids are excluded. Of note, patients who required a single dose of corticosteroids on days receiving radiation treatment do not require a 2-week washout. Follow-up brain imaging after central nervous system (CNS)-directed therapy must show no evidence of progression and patient should be clinically stable for at least 1 month. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. However, patients with concurrent malignancy that is progressing or requiring active treatment are excluded\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be of class 2B or better\n* The effects of the combination ZEN003694 (ZEN-3694) and talazoparib on the developing human fetus are unknown. For this reason, and because BET inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately\n* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 7 months after completion of study drug administration\n* Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior tubal ligation (\\>\u002F= 1 year before screening), total hysterectomy, or menopause (defined as 12 consecutive months of amenorrhea)\n* Ability to understand and the willingness to sign a written informed consent document\n\nExclusion Criteria:\n\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or talazoparib\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or P-gp, strong inhibitors of BCRP, sensitive substrates of CYP1A2, proton-pump-inhibitors (H2 antagonists are allowed), and herbal medications\u002Fpreparations (vitamins are allowed) are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 (ZEN-3694). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.\n* Patients with uncontrolled intercurrent illness\n* Patients with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is a BET inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 month following the last dose of the study drug. These potential risks may also apply to other agents used in this study\n* Patients who are involved in the planning and\u002For conduct of the study\n* Patients who are unable or unwilling to swallow pills\n* Active infection requiring intravenous (IV) antibiotics, or other uncontrolled intercurrent illness requiring hospitalization\n* Patients receiving any medications or substances that are factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Patients with radiation to \\> 25% of the bone marrow\n* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694) or talazoparib\n* Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor\n* Patients with cerebrovascular accident (CVA), myocardial infarction, or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib\n* Patients with impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 (ZEN-3694) or talazoparib\n* Patients that have had major surgery other than diagnostic surgery, dental surgery, or stenting within 4 weeks prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib",{"count":448,"type":21},88,[66],"This phase II trial tests whether ZEN003694 (ZEN-3694) in combination with talazoparib works to shrink tumors in patients with solid tumors that are unlikely to be cured or controlled with treatment and that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Another aim of this study is to find out if, and how, patients' genes influence their response to this specific drug combination. For this part of the study, investigators will run tests using samples of patients' tumor tissue and blood that will be collected during the study. ZEN-3694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that overproduce BET protein. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Genes are pieces of the DNA code that individuals inherit from their parents. Some genes work to protect against cancer by correcting damage that can occur in the DNA when cells divide. BRCA1 and BRCA2 are two examples of these types of genes, and they are called tumor-suppressor genes. For example, if a person has a mutation in a BRCA1\u002F2 gene they have a greatly increased risk of developing breast and ovarian cancer because their cells may no longer be able to completely repair damaged DNA. It is the accumulation of DNA damage which causes a cell to change into a cancerous cell. Other genes are also involved in this process, and these are called DNA damage repair genes. The KRAS mutation is a change in a protein in normal cells. Normally KRAS serves as an information hub for signals in the cell that lead to cell growth, but when there is a mutation in KRAS it signals too much and cells grow without being told to, which causes cancer. Combination therapy with ZEN-3694 and talazoparib may be effective at slowing or stopping tumor growth in patients with advanced cancer.",[69,35,41],{"date":356,"type":47},{"date":454,"type":47},"2022-11-14",{"date":456,"type":21},"2027-12-31",{"name":53,"class":54},{"id":459,"slug":460,"hasResults":12,"nctId":461,"briefTitle":462,"officialTitle":463,"acronym":4,"eligibilityCriteria":464,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":465,"targetDuration":4,"studyType":22,"phases":467,"briefSummary":468,"conditions":469,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":470,"lastUpdatePostDateStruct":471,"startDateStruct":472,"completionDateStruct":474,"leadSponsor":476,"locationsCount":161},"100519451","phase-1-autologous-cd8-and-cd4-transgenic-t-cells-expressing-high-affinity-krasg12v-mutation-specific-t-cell-receptors-fh-a11krasg12v-tcr-in-treating-patients-with-metastatic-solid-tumor-cancers-with-kras-g12v-mutations-100519451","NCT06043713","Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity KRASG12V Mutation-Specific T Cell Receptors (FH-A11KRASG12V-TCR) in Treating Patients With Metastatic Solid Tumor Cancers With KRAS G12V Mutations","Phase I Study of Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity KRASG12V Mutation-Specific T Cell Receptors in Participants With Metastatic Solid Tumors With KRAS G12V Mutations","Inclusion Criteria:\n\n* LEUKAPHERESIS: Diagnosis of metastatic solid tumor\n* LEUKAPHERESIS: Tissue confirmation of solid tumor. Confirmation of diagnosis must be or have been performed by internal pathology review of archival biopsy material or other pathologic material at Fred Hutch\u002FUniversity of Washington Cancer Consortium (UWMC)\n* LEUKAPHERESIS: HLA-A\\*11:01 confirmed through HLA typing at a clinically accredited laboratory\n* LEUKAPHERESIS: Previously documented KRASG12V mutation in tumor or plasma cell-free deoxyribonucleic acid (cfDNA) specimens by polymerase chain reaction (PCR) or next-generation sequencing (NGS) test\n* LEUKAPHERESIS: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm, unless lymph node in which case short axis must be ≥ 15 mm. Baseline imaging (for example, diagnostic CT chest\u002Fabdomen\u002Fpelvis and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) if clinically indicated, must be obtained within 8 weeks of the first planned T cell infusion. MRI can be substituted for CT in participants unable to have CT contrast\n* LEUKAPHERESIS: Participants must be willing to undergo tumor biopsy for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +\u002F- 1 week after the 2nd infusion (if applicable), if safe and feasible (these time windows may vary due to manufacturing or clinical reasons). Should there be no tumor tissue that is accessible for biopsy, subjects will still be considered for participation, at the discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled. Patients can also refuse biopsies at any time after enrollment\n* LEUKAPHERESIS: Participants must be at least two weeks or five half-lives (for small molecules) from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates and denosumab are permitted\n* LEUKAPHERESIS: Participants must have progressed on or be intolerant to at least one lines of prior therapy including any targeted therapies indicated for subjects with each of the tumor types eligible to enroll, as applicable\n* LEUKAPHERESIS: Patients with solid tumors harboring targetable molecular alterations including but not limited to EGFR mutations, ALK, ROS, NTRK fusions, microsatellite instability (MSI)-high, tumor mutational burden (TMB) high, BRAF v600 mutations, HER2 amplifications, must have been treated or refused treatment with applicable targeted therapies, as applicable\n* LEUKAPHERESIS: Fertile male and female participants must be willing to use an effective contraceptive method before, during, and for at least 4 months after the last A11KRASG12V-TCR infusion\n* LEUKAPHERESIS: 18 years or older at the time of enrollment\n* LEUKAPHERESIS: Capable of understanding and providing a written informed consent\n* LEUKAPHERESIS: Eastern Cooperative Oncology Group (ECOG) performance status of =\\\u003C 1\n\n  * No uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days\n* LEUKAPHERESIS: No uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days\n* LEUKAPHERESIS: Renal: Creatinine clearance \\>= 50 ml\u002Fmin by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or 24-hour urine clearance\n* LEUKAPHERESIS: Hepatic: Total bilirubin \\\u003C 2.0 mg\u002FdL\n* LEUKAPHERESIS: Hepatic: Aspartate transferase (AST) and alanine transaminase (ALT) \\\u003C 5x upper limit of normal (ULN)\n* LEUKAPHERESIS: Hepatic: Participants with suspected Gilbert syndrome may be included if total bilirubin (Bili) \\> 3 mg\u002FdL but no other evidence of hepatic dysfunction\n* LEUKAPHERESIS: Cardiac: Participants 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and LVEF must be \\>= 35%. Cardiac evaluation for other participants is at the discretion of the treating physician\n* LEUKAPHERESIS: Hematologic: Absolute neutrophil count (ANC) \\>= 1000 cells\u002F mm\\^3\n* LEUKAPHERESIS: Nutrition: Albumin \\>= 3 g\u002FdL\n* START OF TREATMENT: Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \\>= 10 mm, unless lymph node in which case short axis must be \\>= 15 mm. Baseline imaging (for example, diagnostic CT chest\u002Fabdomen\u002Fpelvis and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 8 weeks of the first planned T cell infusion. MRI can be substituted for CT in participants unable to have CT contrast\n* START OF TREATMENT: Participants must be willing to undergo tumor biopsy for research purposes if safe and feasible at baseline (prior to first T cell infusion), 2-3 weeks after the first T cell infusion, and approximately 2 weeks +\u002F- 1 week after the 2nd infusion (if applicable), if safe and feasible (these windows may vary due to manufacturing or clinical reasons). Should there be no tumor tissue that is accessible for biopsy, subjects will still be considered for participation, at discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons, biopsies may be cancelled or rescheduled\n* START OF TREATMENT: Participants must be at least two weeks from last systemic treatment: At least 2 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, vaccines), or chemotherapy cancer treatment. At least five half-lives must have passed from treatment with small molecules or other investigational agents. There is no washout period for radiation, so long as radiated lesion is not the lesion being evaluated for RECIST measurements on the protocol. Bisphosphonates and denosumab are permitted\n* START OF TREATMENT: ECOG performance status of =\\\u003C 1\n* START OF TREATMENT: Renal: Creatinine clearance \\>= 50 ml\u002Fmin by CKD-EPI or 24-hour urine clearance\n\n  * Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement\n* START OF TREATMENT: Hepatic: Total bilirubin \\\u003C 2.0 mg\u002FdL\n\n  * Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement\n* START OF TREATMENT: AST and ALT \\\u003C 5x upper limit of normal (ULN)\n* START OF TREATMENT: Participants with suspected Gilbert syndrome may be included if total Bili \\> 3 mg\u002Fdl but no other evidence of hepatic dysfunction\n* START OF TREATMENT: Pulmonary: =\\\u003C grade 1 dyspnea and oxygen saturation of arterial blood (SaO2) \\>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, participants with forced expiratory volume in the first second (FEVI) \\>= 50% of predicted and diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected) \\>= 40% of predicted will be eligible\n\n  * Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement\n* START OF TREATMENT: Hematologic: ANC \\>= 1000 cells\u002F mm\\^3\n\n  * Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement\n* START OF TREATMENT: Nutrition: Albumin \\>= 3 g\u002FdL\n\n  * Exceptions may be at the discretion of the PI to allow participants with organ function affected by their organ-specific tumor involvement\n* START OF TREATMENT: Participants with a history of chronic obstructive pulmonary disease (COPD), emphysema, or greater than 30 pack year smoking history should undergo PFTs and meet the following criteria:\n\n  * FEVI \\>= 50% of predicted and DLCO (corrected) \\>= 40% of predicted will be eligible\n\nExclusion Criteria:\n\n* LEUKAPHERESIS: Prior solid organ transplant or allogeneic hematopoietic stem cell transplant: Kidney transplant participants will be considered on a case-by-case basis requiring discussion with PI. If the participant has had a kidney transplant, participant must have dialysis access, dialysis plan, supportive nephrologist, willingness to stop transplant immunosuppression, and express understanding that rejection is possible outcome. Dialysis or costs related to transplant kidney will not be supported by the study. Participants having had any other solid organ transplants will be excluded, as will those with any history of allogeneic hematopoietic stem cell transplant\n* START OF TREATMENT: Pregnancy, breastfeeding, or expecting to conceive or father children for the duration of the trial through 4 months after last T-cell infusion. Participants of childbearing potential must have a negative serum pregnancy test within the 2 weeks (14 days) preceding T cell infusion. Childbearing potential is defined as women who have not been surgically sterilized and who are not post-menopausal (free of menses for at least 1 year)\n* START OF TREATMENT: Active autoimmune disease: Participants with active autoimmune disease requiring immunosuppressive therapy are excluded. Case by case exemptions are possible with approval by PI\n* START OF TREATMENT: Corticosteroid therapy at a dose equivalent of \\> 0.5 mg\u002Fkg of prednisone per day. The following treatments are permitted: intranasal, inhaled, topical, or local steroid applications; systemic corticosteroids at physiologic doses equivalent to no more than \\> 0.5 mg\u002Fkg\u002Fday prednisone; steroids as premedication for contrast dye allergy\n* START OF TREATMENT: Concurrent use of other investigational anti-cancer agents\n* START OF TREATMENT: Active uncontrolled infection: Human immunodeficiency virus (HIV) positive participants on highly active antiretroviral therapy (HAART) with a CD4 count \\> 500 cells\u002Fmm\\^3 are considered controlled, as are individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have hepatitis well controlled on medication\n* START OF TREATMENT: Uncontrolled concurrent illness: Participants may not have uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* START OF TREATMENT: Untreated brain metastases: Participants with small asymptomatic brain metastases (\\\u003C 1 cm) or those with brain metastases previously treated and controlled with surgery or radiotherapy will be considered for inclusion at discretion of PI, so long as all other eligibility criteria are met\n* START OF TREATMENT: Active treatment for prior immune related adverse event to any immunotherapy: Participants receiving ongoing treatment for prior serious immune-related adverse events are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of up to 0.5mg\u002Fkg\u002Fday prednisone per day, unless otherwise approved by PI\n* START OF TREATMENT: Other medical, social, or psychiatric factor that interferes with medical appropriateness and\u002For ability to comply with study, as determined by the PI\n* START OF TREATMENT: Known allergic reactions to any of the components of study treatments\n* START OF TREATMENT: Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days",{"count":466,"type":21},24,[24],"This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ transgenic T cells expressing high affinity KRASG12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR) and to see how well they work in treating patients with solid tumor cancers that has spread from where it first started (primary site) to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize KRAS G12V, a protein on the surface of tumor cells. These KRAS G12V-specific T cells may help the body's immune system identify and kill KRAS G12V solid cancer tumor cells.",[35],"2026-06-15",{"date":356,"type":47},{"date":473,"type":47},"2023-12-15",{"date":475,"type":21},"2028-01-01",{"name":139,"class":140},{"id":478,"slug":479,"hasResults":12,"nctId":480,"briefTitle":481,"officialTitle":482,"acronym":4,"eligibilityCriteria":483,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":484,"targetDuration":4,"studyType":22,"phases":486,"briefSummary":487,"conditions":488,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":494,"lastUpdatePostDateStruct":495,"startDateStruct":496,"completionDateStruct":498,"leadSponsor":500,"locationsCount":109},"100492388","phase-1-testing-the-combination-of-the-anti-cancer-drugs-temozolomide-and-m1774-to-evaluate-their-safety-and-effectiveness-100492388","NCT05691491","Testing the Combination of the Anti-Cancer Drugs Temozolomide and M1774 to Evaluate Their Safety and Effectiveness","A Phase 1\u002F2 Trial Evaluating the Combination of Temozolomide and the Ataxia Telangiectasia and Rad3-Related Inhibitor M1774","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed diagnosis of metastatic advanced cancer.\n* In dose escalation, any solid tumor patients with either O6-methylguanine DNA methyltransferase (MGMT) promoter hypermethylation positivity on testing \u002F pre-screening of archival tissue OR an extracranial solid tumor where TMZ is considered a standard of care per National Comprehensive Cancer Network (NCCN) guidelines (neuroendocrine tumor, small cell lung cancer, melanoma or soft tissue sarcoma). The tumor lesion must be safely accessible to a mandatory biopsy. Patients with MGMT promoter hypermethylated colorectal cancer must be mismatch repair proficient \u002F microsatellite stable.\n* In phase 2, only patients with mismatch repair proficient \u002F microsatellite stable colorectal cancer that have MGMT promoter hypermethylation positivity on pre-screening of archival tissue will be eligible.\n* In dose escalation, patients must have progressed after treatment with all available therapies including immunotherapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Patients may not have previously received temozolomide or an ataxia telangiectasia and rad3-related (ATR) inhibitor.\n* For patients with mismatch repair proficient \u002F microsatellite stable colorectal cancer in the phase 2 portion, patients must have received prior therapy with 1 or more systemic therapies in the metastatic setting that includes 5-fluorouracil, irinotecan, and oxaliplatin. Patients with microsatellite stable colorectal cancer (mCRC) need to have had exposure, unless contraindicated, to all 3 of oxaliplatin, irinotecan, and fluoropyrimidine (FP).\n\nThe use of 5-fluorouracil and oxaliplatin in the adjuvant setting is acceptable, provided the development of metastatic disease was less than 6 months after the completion of adjuvant therapy.\n\nPatients with a prior hypersensitivity reaction to oxaliplatin in the adjuvant setting do not require retreatment in the metastatic setting.\n\n* Age \\>=18 years. Because no dosing or adverse event data are currently available on the use of M1774 in combination with temozolomide in patients \\\u003C 18 years of age, children are excluded from this study.\n* Measurable disease on CT and\u002For MRI per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria.\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (or Karnofsky \\>= 60%).\n* Hemoglobin \\>=10 g\u002FdL (No blood transfusions are allowed within 14 days of cycle 1 day 1 \\[C1D1\\]).\n* White blood cells (WBC) \\> 3 x 10\\^9\u002FL.\n* Absolute neutrophil count \\>= 1,500\u002FmcL.\n* Platelets \\>= 100,000\u002FmcL.\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN).\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine-aminotransferase (ALT) (serum glutamic-pyruvic transaminase \\[SGPT\\]) =\\\u003C 3 x institutional ULN except for when liver metastases are present, in which case they must be =\\\u003C 5 x institutional ULN.\n* Glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin\u002F1.73 m\\^2.\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for 4 weeks.\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.\n* The effects of M1774 on the developing human fetus are unknown. For this reason and because ATR inhibitors agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after completion of M1774 administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of M1774 administration.\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia and neuropathy, which may be =\\\u003C grade 2.\n* History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to M1774 or temozolomide, including dacarbazine.\n* Patients with uncontrolled intercurrent illness.\n* Pregnant women are excluded from this study because M1774 is an ATR inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M1774 breastfeeding should be discontinued if the mother is treated with M1774. These potential risks also apply to temozolomide.\n* Patients with a prior history of ataxia telangiectasia.\n* Patients who are not able to swallow orally administered medication or have gastrointestinal disorders likely to interfere with absorption of the study medication.\n* Patients who cannot discontinue proton-pump inhibitors (PPIs) while taking M1774. H-2 receptor antagonists are allowed but should not be taken within 12 hours before or 2 hours after M1774. Antacids are also allowed, but should not be taken 2 hours before 2 hours after M1774.\n* Extensive RT involving greater than 30% of the bone marrow is not permitted during the study.\n* A Fridericia's correction formula (QTcF) \\> 480 ms is exclusionary given the potential for QT.",{"count":485,"type":21},42,[24,66],"This phase I\u002FII trial studies the side effects and best dose of temozolomide and M1774 and how well they works in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and may have spread to nearby tissue, lymph nodes, or distant parts of the body (advanced). Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. M1774 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Adding M1774 to temozolomide may shrink or stabilize cancer for longer than temozolomide alone.",[69,489,490,35,491,492,493],"Advanced Microsatellite Stable Colorectal Carcinoma","Hematopoietic and Lymphatic System Neoplasm","Metastatic Microsatellite Stable Colorectal Carcinoma","Stage III Colorectal Cancer AJCC v8","Stage IV Colorectal Cancer AJCC v8","2026-06-13",{"date":354,"type":47},{"date":497,"type":47},"2023-09-28",{"date":499,"type":21},"2027-03-01",{"name":53,"class":54},{"id":502,"slug":503,"hasResults":12,"nctId":504,"briefTitle":505,"officialTitle":506,"acronym":4,"eligibilityCriteria":507,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":508,"targetDuration":4,"studyType":22,"phases":510,"briefSummary":512,"conditions":513,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":522,"lastUpdatePostDateStruct":523,"startDateStruct":525,"completionDateStruct":527,"leadSponsor":528,"locationsCount":161},"100624088","phase-4-morning-versus-afternoon-administration-of-immunotherapy-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-knight-shift-study-100624088","NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases",{"count":509,"type":21},160,[511],"PHASE4","This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.",[514,515,516,517,69,518,519,520,243,244,176,35,178,179,521,250,251,252,267,180,181],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","2026-06-10",{"date":524,"type":47},"2026-06-12",{"date":526,"type":47},"2026-06-08",{"date":397,"type":21},{"name":529,"class":140},"OHSU Knight Cancer Institute",{"id":531,"slug":4,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":532,"targetDuration":4,"studyType":22,"phases":533,"briefSummary":25,"conditions":534,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":522,"lastUpdatePostDateStruct":535,"startDateStruct":537,"completionDateStruct":538,"leadSponsor":539,"locationsCount":55},"100603507",{"count":20,"type":21},[24],[27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42],{"date":536,"type":47},"2026-06-11",{"date":49,"type":21},{"date":51,"type":21},{"name":53,"class":54},{"id":541,"slug":542,"hasResults":12,"nctId":543,"briefTitle":544,"officialTitle":545,"acronym":4,"eligibilityCriteria":546,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":547,"targetDuration":4,"studyType":22,"phases":549,"briefSummary":550,"conditions":551,"keywords":555,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":522,"lastUpdatePostDateStruct":557,"startDateStruct":558,"completionDateStruct":560,"leadSponsor":562,"locationsCount":55},"100564533","phase-2-pemetrexed-response-in-relation-to-tumor-alterations-of-gene-status-for-the-treatment-of-patients-with-metastatic-urothelial-bladder-cancer-and-other-solid-tumors-100564533","NCT06630416","Pemetrexed Response in Relation to Tumor Alterations of Gene Status for the Treatment of Patients With Metastatic Urothelial Bladder Cancer and Other Solid Tumors","A Phase II Trial to Evaluate Pemetrexed Response in Relation to Tumor Alterations of Gene Status in Patients With Previously Treated Metastatic Urothelial Carcinoma and Other Solid Tumors","Inclusion Criteria:\n\n* Patients must have pathologically or cytologically confirmed metastatic urothelial bladder carcinoma (Arm A) or other metastatic\u002Flocally-advanced solid malignancy (Arm B) and MLL4- protein (KMT2D-gene) or UTX-protein (KDM6A-gene) or MTAP loss of function mutation including but not limited to SNVs that cause truncation, CNVs, and indels confirmed by next generation sequencing or immunohistochemistry techniques.\n* Patients must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), measured preferably by computed tomography (CT) scan.\n* Patients who have received any prior neoadjuvant or systemic chemotherapy are eligible.\n\n  * Notes:\n\n    * Patients must have progressive disease despite two prior lines of therapy in the metastatic setting or locally advanced setting unless the patient was not suitable for an approved second line regimen due to intolerance or another clinical factor;\n    * Treatment cannot have included prior pemetrexed. Any prior intravesical therapy, or immunotherapy is allowed. At least 3 weeks (21 days) wash-out period since prior chemotherapy or radiation therapy or targeted agent is required.\n* Patients must be aged ≥ 18 years.\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n* Patients must have adequate organ and bone marrow function as defined:\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL (growth factor allowed and can be added at the discretion of the treating oncologist)\n* Hemoglobin (Hgb) ≥ 8.5 g\u002FdL (without the need for transfusion within the previous one week)\n* Platelets (PLT) ≥ 100,000\u002FmL (without the need for platelet transfusion within the previous one week)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin ≤ 3.0 mg\u002FdL\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present\n* Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present\n* Creatinine clearance ≥ 45 mL\u002Fmin\u002F1.73 m\\^2 using the standard Cockcroft and Gault formula\n* Patients must have the ability to comply with the administration of supplemental therapies including folic acid, vitamin B12 and steroids as directed by study team and as per standard of care and institutional standards and practice for pemetrexed use.\n* Patients must be able swallow oral medication or not have problems\u002Fdiseases that affect absorption or oral medication.\n* Patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration. Please note this lab is not a requirement for eligibility, however, if it was previously done as part of the patient's health care, it should be documented for eligibility.\n* Patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Please note this lab is not a requirement for eligibility, however, if the lab has been completed previously as part of the patient's health care, then it should be documented for eligibility.\n* Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with a known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Please note this lab is not a requirement for eligibility, however if it was previously done as part of the patient's health care, it should be documented for eligibility.\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.\n* Pemetrexed is known to be teratogenic. For this reason, patients of child-bearing potential (POCBP) and their partners with sperm-producing reproductive capacity must agree to use adequate contraception from time of informed consent, for the duration of study participation, and for 180 days following completion of pemetrexed therapy. Should a POCBP become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must also agree to use adequate contraception with partners of childbearing potential from time of informed consent, for the duration of study participation, and 180 days after completion of administration\n\n  * Note: A POCBP is any patient (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) with an egg-producing reproductive tract who meets the following criteria:\n\n    * Has not undergone a hysterectomy or bilateral oophorectomy\n    * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months)\n* POCBP must have a negative pregnancy test prior to registration on study.\n* The ability to interrupt nonsteroidal anti-inflammatory drugs (NSAIDS) or aspirin at higher dose (\\> 1.3 g per day) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.\n* Patients must be able to understand and voluntarily sign a written informed consent and willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.\n\nExclusion Criteria:\n\n* Patients who received prior pemetrexed containing chemotherapy.\n* Patients who have had chemotherapy or radiotherapy ≤ 21 days (prior to planned treatment start date). For palliative radiation, 5 day wash out is sufficient.\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia, neuropathy and other non-significant adverse events deemed not clinically significant by the treating investigator, adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0).\n* Patients who are receiving any other investigational agents. A 21 day wash out period will be required after discontinuation of an investigational agent prior to first day of study treatment.\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed.\n* Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:\n\n  * Ongoing or active infection requiring systemic treatment\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints\n* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.\n\n  * Note: To be eligible for this trial, patients should be class 2B or better\n* Patients with presence of third space fluid which cannot be controlled by drainage\n\n  * Note: For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy\n* Has received the final dose of any of the following treatments\u002F procedures with the specified minimum intervals before first dose of study drug:\n\n  * Focal radiation therapy - 7 days\n  * Surgery with general anesthesia - 7 days\n  * Surgery with local anesthesia - 3 days\n  * For palliative radiation - 5 days\n* Patients of child bearing (POCB) potential who are pregnant or nursing.\n\n  * Note: Registration of patients is completed in Northwestern Oncology Trial Information System (NOTIS)",{"count":548,"type":21},64,[66],"This phase II trial tests how well pemetrexed works in treating patients with urothelial bladder cancer and other solid tumors that have spread from where they first started (primary site) to other places in the body (metastatic) with mutations that result in a loss of function in the MLL4-protein\u002FKMT2D-gene or UTX-protein\u002FKDM6A-gene or MTAP enzyme. Loss of function due to a genetic mutation means a gene's activity may be reduced or eliminated. Mutations that result in a loss of function in the MLL4-protein or KMT2D-gene are found in 9.96% of all cancers including bladder carcinoma patients, esophageal squamous cell carcinoma and esophageal adenocarcinoma patients. In addition, mutations that result in a loss of function in the UTX-protein or KDM6A-gene are found in approximately 5% of all tumors, including bladder cancers, endometrial cancer, and esophagogastric cancer amongst many other tumor types. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid and may kill tumor cells. Giving pemetrexed may increase response in patients with metastatic urothelial bladder cancer and other solid tumors with the loss of function in the MLL4-protein\u002FKMT2D-gene or UTX-protein\u002FKDM6A-gene or MTAP enzyme.",[552,35,553,554],"Metastatic Bladder Urothelial Carcinoma","Stage IV Bladder Cancer AJCC v8","MTAP Deletion",[556],"KMT2D (gene)\u002FMLL4 (protein) or KDM6A (gene)\u002FUTX (protein) or MTAP loss of function mutations",{"date":524,"type":47},{"date":559,"type":47},"2024-11-27",{"date":561,"type":21},"2030-05-10",{"name":563,"class":140},"Northwestern University",{"id":565,"slug":566,"hasResults":12,"nctId":567,"briefTitle":568,"officialTitle":569,"acronym":4,"eligibilityCriteria":570,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":571,"targetDuration":4,"studyType":22,"phases":573,"briefSummary":574,"conditions":575,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":522,"lastUpdatePostDateStruct":578,"startDateStruct":579,"completionDateStruct":581,"leadSponsor":583,"locationsCount":584},"100500986","phase-1-testing-the-addition-of-an-anti-cancer-drug-zen003694-to-the-usual-chemotherapy-treatment-capecitabine-for-metastatic-or-unresectable-cancers-100500986","NCT05803382","Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers","Phase I Trial of ZEN003694 (ZEN-3694) in Combination With Capecitabine in Patients With Solid Tumors","Inclusion Criteria:\n\n* Dose Escalation additional criteria: Patients must have histologically confirmed cancer that is metastatic or unresectable and must have progressed on standard therapies which would have included fluorouracil (5-FU) or capecitabine\n* Dose Escalation additional criteria specifically for colorectal cancer (CRC) patients: Willingness and ability to undergo a pre-treatment biopsy\n* Dose Expansion additional criteria: Patients must have histologically confirmed CRC that is metastatic or unresectable and must have progressed on standard therapies which would have included 5-FU or capecitabine\n* Dose Expansion additional criteria: Willingness and ability to undergo pre- and on- treatment biopsies\n* Patients must have measurable disease\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with capecitabine in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky \\>= 60%)\n* Availability of archival tumor tissue at the time of patient enrollment for molecular profiling studies\n* Prior to study dosing, previous systemic therapy must have been completed for at least five half-lives or 2 weeks, whichever is shorter\n* Absolute neutrophil count \\>= 1,000\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Total bilirubin =\\\u003C 1.5 institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 3 x institutional ULN\n* Glomerular filtration rate (GFR) \\>= 50 mL\u002Fmin\u002F1.73 m\\^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients should be New York Heart Association Functional Classification of class 2B or better\n* The effects of ZEN003694 (ZEN-3694) and capecitabine on the developing human fetus are unknown. For this reason and because BET inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential and men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of ZEN003694 (ZEN-3694) and capecitabine administration\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n\nExclusion Criteria:\n\n* Previous treatment with BET inhibitors\n* History of inability to tolerate capecitabine at the projected treatment dose on this trial\n* Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed\n* Treatment for HIV, hepatitis B or hepatitis C only if this interferes with the current treatment (e.g. through drug-drug interactions)\n* Gastrointestinal pathology or history that adversely impacts the ability to take or absorb oral medication\n* Hepatic tumor burden \\> 30% or peritoneal carcinomatosis\n* Untreated\u002Funcontrolled central nervous system (CNS) disease\n* Known dihydropyrimidine dehydrogenase (DPD) deficiency\n* Severe intercurrent illness or comorbidity\n* Inability to comply with the protocol and\u002For not willing or who will not be available for follow-up assessments\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia and neuropathy up to and including grade 2\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or other agents used in study\n* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors of CYP3A4 must be discontinued at least 7 days, and inducers 14 days prior to the first dose of ZEN003694 and capecitabine. Substrates of CYP1A2 with narrow therapeutic window must be avoided while taking ZEN003694\n* Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued if the mother is treated with ZEN003694 (ZEN-3694). These potential risks may also apply to other agents used in this study",{"count":572,"type":21},30,[24],"This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with the usual treatment with capecitabine in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and that it has progressed on previous standard treatment. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Capecitabine is in a class of medications called antimetabolites. It is taken up by cancer cells and breaks down into fluorouracil, a substance that kills cancer cells. Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors.",[576,35,493,577,41],"Metastatic Colorectal Carcinoma","Unresectable Colorectal Carcinoma",{"date":536,"type":47},{"date":580,"type":47},"2023-11-08",{"date":582,"type":21},"2027-06-30",{"name":53,"class":54},22,{"id":586,"slug":587,"hasResults":12,"nctId":588,"briefTitle":589,"officialTitle":590,"acronym":4,"eligibilityCriteria":591,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":592,"targetDuration":4,"studyType":22,"phases":594,"briefSummary":595,"conditions":596,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":522,"lastUpdatePostDateStruct":597,"startDateStruct":598,"completionDateStruct":600,"leadSponsor":602,"locationsCount":161},"100355402","phase-2-durvalumab-in-combination-with-chemotherapy-in-treating-patients-with-advanced-solid-tumors-durva-trial-100355402","NCT03907475","Durvalumab in Combination With Chemotherapy in Treating Patients With Advanced Solid Tumors, DURVA+ Trial","DURVA+ : Evaluation of the Safety and Pharmacodynamics of Anti-PD-L1 Antibody Durvalumab in Combination With Chemotherapy in Patients With Advanced Solid Tumors","Inclusion Criteria:\n\n* Patients with histologically documented metastatic or locally advanced (not amenable to surgery) solid tumors whose disease has progressed following at least one line of standard therapy and\u002For no standard of treatment exists that has been shown to prolong survival.\n\n  * If anti-PD-1 or one of the 6 chemotherapy agents is standard-of-care, prior therapy with the agent would not be required.\n* Patient must have tumor amenable to biopsy and be willing to undergo a tumor biopsy.\n\n  * Flash frozen tissue collected as part of another study or from a procedure performed due to medical necessity may be acceptable as the baseline sample if the samples were collected within 3 months prior to registration and the patient has not received any investigational or targeted treatment since that time.\n  * A patient who cannot be safely biopsied may be considered for the study upon discussion with Principal Investigator.\n* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \\>= 20 mm with conventional techniques or as \\>= 10 mm with spiral computed tomography (CT) scan.\n* Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment. Patients with prostate cancer may continue luteinizing hormone-releasing hormone (LHRH) agonists or antagonists.\n* Age ≥ 18 years. Children are excluded from this study, but may be eligible for future pediatric trials.\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2.\n* Absolute neutrophil count \\>= 1,000\u002FuL (mcL).\n* Platelets \\>= 100,000\u002FuL (mcL).\n* Total bilirubin \\\u003C 1.5 x institutional upper limit of normal.\n\n  * This will not apply to patients with confirmed Gilbert syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only at the discretion of the principal investigator (PI), study chair or their designee.\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 3 x institutional upper limit of normal, or up to 5 x upper limit of normal (ULN) if liver metastases are present.\n* Calculated creatinine clearance \\> 40 mL\u002Fmin by the Cockcroft-Gault formula\n* Any prior systemic therapy (including checkpoint inhibitors), or major surgery must have been completed \\>= 3 weeks (\\> 6 weeks for nitrosoureas or mitomycin C) or 5 half-lives of the agent, whichever is shorter, prior to enrollment on protocol, and toxicity from prior treatment must have recovered to eligibility levels. Radiation therapy must have been completed \\>= 1 week prior to starting treatment. Radiofrequency ablation (RFA) of localized lesions should have been performed \\>= 1 week prior to starting treatment. All radiation-related toxicity must have resolved to \\\u003C grade 2.\n\n  * Palliative radiotherapy is permitted between disease progression on Arm 1 and crossover to a combination therapy arm (Arms 2-7), provided there is a washout period of \\>= 1 week and any toxicity from radiation has resolved to \\\u003C grade 2\n  * Patients on any arm may receive palliative radiotherapy or loco-regional ablative therapy and remain on study, provided the radiation is not delivered to the target lesion and the patient does not have tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST)\n* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon-alpha or interleukin-2) must have been completed at least 3 weeks before the first dose of durvalumab.\n* Body weight \\> 30 kg.\n* Human immunodeficiency virus (HIV)-infected (HIV1\u002F2 antibody-positive) patients may participate if they meet all the following eligibility requirements:\n\n  * They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on this same regimen; the most recent undetectable viral load must be within the past 12 weeks.\n  * They must have a CD4 count \\>= 250 cells\u002FuL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \\\u003C 200 cells\u002FuL over the past 2 years, unless it was deemed related to chemotherapy-induced bone marrow suppression.\n\n    * For patients who have received chemotherapy in the past 6 months, a CD4 count \\\u003C 250 cells\u002FuL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy.\n  * They must have an undetectable viral load and a CD4 count \\>= 250 cells\u002FuL within 28 days of enrollment.\n  * They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.\n  * Monitoring for HIV-infected patients should include:\n\n    * Viral load and CD4 count every 8-10 weeks.\n* The effects of targeted agents on the developing human fetus are unknown. The cytotoxic agents chosen for combination with durvalumab adversely affect human fertility and gestation. For these reasons, women of childbearing potential and men must agree to use highly effective contraception prior to study entry for the duration of study participation and for 6 months following the last dose of a study drug.\n* Because there may be a risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued while the patient is on this trial and for 6 months following the last dose of study drug.\n* Patients should be willing not to donate blood while participating in this study or for at least 90 days following the last dose of study drug.\n* Left ventricular ejection fraction greater than 50% or the institutional lower limit of normal by echocardiography (ECHO) at entry (patients enrolling on Arm 3 only).\n* Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Patients who received prior therapy with a checkpoint inhibitor and were taken off drug for serious adverse events are excluded. Patients who had prior CTLA-4 inhibitor treatment and did not experience serious adverse events are eligible for all arms. Patients who had prior PD-L1\u002FPD-1 inhibitor treatment and did not experience serious adverse events are excluded from the durvalumab monotherapy arm but are eligible for the chemotherapy combinations.\n* Patients with pancreatic cancer, prostate cancer, or microsatellite stable (MSS) colorectal cancer, or other histologies where clinical evidence exists that single-agent inhibition of PD-L1\u002FPD-1 has minimal activity will not receive single-agent durvalumab but may be eligible to receive this agent with chemotherapy (Arms 2-7).\n* Women who are pregnant or breastfeeding.\n* Patients who are receiving any other investigational agents. Patients on other trials will be eligible as long as they are no longer receiving study treatment.\n* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[e.g., colitis or Crohn's disease\\], diverticulitis \\[with the exception of diverticulosis\\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\\]). The following are exceptions:\n\n  * Patients with vitiligo or alopecia\n  * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement\n  * Any chronic skin condition that does not require systemic therapy\n  * Patients without active disease in the last 5 years may be included but only after consultation with the study physician\n  * Patients with celiac disease controlled by diet alone\n* History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (e.g. bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. Patients with active tuberculosis (TB) are also excluded.\n* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions:\n\n  * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)\n  * Systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or glucocorticoid equivalent dose of another steroid\n  * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)\n* Patients should not be vaccinated with live attenuated vaccines within 30 days before starting or after completing durvalumab treatment.\n* Patients who have a history of seizures will not be eligible, unless they have either not had seizures or have been on stable doses of anti-seizure medicine and had no seizures for 4 weeks, in which case they will be eligible. Patients taking enzyme-inducing anticonvulsants (i.e., carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone) will only be eligible for Arm 1 (durvalumab monotherapy) and Arm 2 (durvalumab + gemcitabine).\n* Patients receiving warfarin are not eligible for Arm 4 (capecitabine) due to the potential for life-threatening interactions. Patients on warfarin are eligible to enroll in one of the other arms provided there is increased vigilance with respect to monitoring international normalized ratio (INR).\n* Patients with uncontrolled intercurrent illness including, but not limited to psychiatric illness\u002Fsocial situations that would limit compliance with study requirements, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the past 6 months, invasive fungal infections, or active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e., quantifiable hepatitis B virus \\[HBV\\]-deoxyribonucleic acid \\[DNA\\] and\u002For positive hepatitis B surface antigen \\[HbsAg\\], quantifiable HCV-ribonucleic acid \\[RNA\\]), are not eligible to participate. Testing for HBV-DNA and HCV-RNA will be mandatory for patients with hepatocellular carcinoma (HCC) only; testing for hepatitis B or other infections for eligibility will be performed only if clinically indicated.\n* History of grade \\>= 2 infusion reactions or allergic reactions to humanized monoclonal antibodies. Exception: patients with a history of grade 2 infusion reactions to checkpoint inhibitors may be eligible if resumption of prior therapies with pre-medications has been documented without recurrence of infusion reactions of any grade; those patients should receive the same pre-medications with the first and subsequent doses of durvalumab.\n* History of primary immunodeficiency.\n* History of allogeneic organ transplant.",{"count":593,"type":21},115,[66],"This phase II trial studies the side effects of durvalumab when given together with chemotherapy in treating patients with solid tumors that have spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine hydrochloride, pegylated liposomal doxorubicin hydrochloride, capecitabine, carboplatin, paclitaxel, and nab-paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with durvalumab may improve how immune cells respond and attack tumor cells.",[70,35],{"date":536,"type":47},{"date":599,"type":47},"2019-07-16",{"date":601,"type":21},"2027-06-01",{"name":53,"class":54},{"id":604,"slug":605,"hasResults":12,"nctId":606,"briefTitle":607,"officialTitle":608,"acronym":4,"eligibilityCriteria":609,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":610,"targetDuration":4,"studyType":22,"phases":612,"briefSummary":613,"conditions":614,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":631,"lastUpdatePostDateStruct":632,"startDateStruct":633,"completionDateStruct":635,"leadSponsor":636,"locationsCount":161},"100421724","phase-2-avapritinib-for-the-treatment-of-ckit-or-pdgfra-mutation-positive-locally-advanced-or-metastatic-malignant-solid-tumors-100421724","NCT04771520","Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors","Phase 2 Study of Avapritinib in Patients With CKIT or PDGFRA Mutation-Positive Malignant Solid Tumors","Inclusion Criteria:\n\n1. The patient (or legally acceptable representative if applicable) provides written informed consent for the study.\n2. Male or female ≥18 years of age on the day of informed consent signing. Adolescent patients aged 12 years and older are allowed with signed assent and parental consent according to institutional guidelines and requirements.\n3. Cohorts 1 and 2: Patient has a locally advanced or metastatic solid tumor and has progressed on appropriate standard therapy, has not shown clinically meaningful benefit to appropriate standard therapy, has no available standard therapy, or has declined appropriate standard therapy.\n\n   • NOTE: Specific solid tumor types include but are not limited to melanoma, breast cancer, lung cancer, gastroesophageal cancer, colorectal cancer, sarcoma, solid tumors NOS, and primary CNS tumors. Patients with any other recurrent solid tumor type with the exception of gastrointestinal stromal tumor (GIST) will be eligible.\n4. Cohort 3: Patient has newly diagnosed IDH wild-type, MGMT-unmethylated glioblastoma. Patients must have received prior treatment with radiation and concurrent temozolomide per standard of care.27 Patients must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.\n5. Measurable disease per the RECIST v1.1 or RANO criteria, as appropriate, for Cohorts 1 and 2. Patients in Cohort 3 can have measurable or non-measurable disease per the RANO criteria.\n\n6 Documented pathogenic CKIT activating mutation (Cohort 1) OR pathogenic PDGFRA activating mutation (Cohort 2) based on Clinical Laboratory Improvement Amendments-certified next-generation sequencing diagnostic test. Cohort 3 should have pathogenic CKIT or PDGFRA activating mutation\u002Famplification based on CLIA-certified NGS diagnostic test. CKIT and PDGFRA mutation pathogenicity will be verified by the MD Anderson Cancer Center's Precision Oncology Decision Support team. Acceptable CKIT\u002FPDGFRA mutations for study eligibility are listed in Appendix E.\n\n7\\. Has available archival tissue for CKIT\u002FPDGFRA mutation (amplification \\[Cohort 3 only\\]) retrospective testing.\n\n8\\. Adequate organ and marrow function as defined below within 7 days of study treatment initiation:\n\n* White blood cell count \\>2,500\u002FµL and \\\u003C15,000\u002FµL\n* Absolute neutrophil count ≥1.5 × 109\u002FL (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)\n* Platelet count ≥75 × 109\u002FL (without transfusion within 2 weeks of laboratory test used to determine eligibility)\n* Hemoglobin ≥9.0 g\u002FdL (without blood transfusion within 7 days of laboratory test used to determine eligibility)\n* Total bilirubin ≤1.5 × upper limit of normal (ULN); if hepatic metastases are present, ≤3.0 × ULN\n* Aspartate transaminase and alanine transaminase ≤2.5 × ULN; if hepatic metastases are present, ≤5.0 × ULN\n* Serum creatinine ≤2.0 × ULN or creatinine clearance ≥45 mL\u002Fmin. 9. Cardiac ejection fraction \\>45% per screening echocardiogram or multigated acquisition scan.\n\n  10\\. Eastern Cooperative Oncology Group performance status of 0-2.\n\n  11\\. Life expectancy ≥3 months.\n\n  12\\. Willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations.\n\n  13\\. Willing to undergo biopsy as required by the study.\n\n  14\\. Females must be postmenopausal (defined as ≥45 years of age with at least 12 months of spontaneous amenorrhea) or premenopausal with documented surgical sterilization (tubal ligation, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or evidence of non-childbearing status for women of childbearing potential (negative serum beta-human chorionic gonadotropin pregnancy test) within 3 days of study treatment initiation.\n\n  15\\. Females of childbearing potential must either abstain from heterosexual intercourse or use a highly effective method of contraception for the course of the study and for 6 weeks after the last dose of study treatment.\n\n  16\\. Males with female partners of reproductive potential must either abstain from sexual intercourse or they and their partners must use a highly effective method of contraception when engaging in sexual intercourse for the course of the study through 30 days after the last dose of study treatment.\n\nExclusion Criteria:\n\nPatients eligible for this study must not meet any of the following criteria:\n\n1. Patients who have GIST.\n2. Patients with tyrosine kinase inhibitor-resistant CKIT mutation V654A or T670I.\n3. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases. Note: Patients with stable brain metastases (defined as asymptomatic or no requirement for high-dose or increasing dose of systemic corticosteroids) and without imminent need of radiation therapy) are eligible (including those with untreated brain metastases). If applicable, patients must have completed brain radiation therapy and recovered adequately from any associated toxicity and\u002For complications prior to eligibility assessment. For patients who have received prior radiation therapy, post-treatment magnetic resonance imaging scan should show no increase in brain lesion size\u002Fvolume.\n4. History of documented congestive heart failure (New York Heart Association functional classification III-IV) or serious cardiac arrhythmias requiring treatment.\n5. QT interval corrected using Fridericia's formula of \\>470 msec.\n6. Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to study treatment initiation.\n7. Prior anticancer chemotherapy, hormone therapy, immunotherapy, targeted therapy, radiation therapy, or surgery within 2 weeks prior to study treatment initiation.\n\n   * NOTE: Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline (except alopecia). Patients with ≤ Grade 2 neuropathy are eligible.\n   * NOTE: If patient received major surgery, she\u002Fhe must have recovered adequately from the toxicity and\u002For complications from the intervention prior to study treatment initiation.\n   * NOTE: Patients in Cohort 3 must have completed radiation and concurrent temozolomide 3-8 weeks prior to study treatment initiation.\n8. Symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.\n9. History of psychotic or depressive disorder. Patients whose disorder is well controlled on a stable antipsychotic or antidepressant medication for at least 12 months prior to study entry will be eligible.\n10. Concomitant use of a known strong cytochrome P450 (CYP)3A4 inhibitor or strong CYP3A4 inducer. The required washout period prior to study treatment initiation is 2 weeks or 5 half-lives, whichever is shortest.\n11. Females who are pregnant or breastfeeding.\n12. Unable to swallow and retain oral medications.\n13. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).\n14. Known additional malignancy that is progressing or requires active treatment. NOTE: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone potentially curative therapy are not excluded.\n15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the investigator.\n16. Prior treatment with an intracerebral agent or bevacizumab (Cohort 3 only).\n17. Prior treatment including radiation, chemotherapy, or immunotherapy for low-grade glioma (Cohort 3 only).",{"count":611,"type":21},50,[66],"This phase II trial studies the effect of avapritinib in treating malignant solid tumors that have a genetic change (mutation) in CKIT or PDGFRA and have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Avapritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Avapritinib may help to control the growth of malignant solid tumors.",[28,215,218,220,70,228,615,616,35,178,617,618,619,620,621,622,623,624,625,626,627,261,493,180,628,270,629,274,630],"Locally Advanced Primary Malignant Central Nervous System Neoplasm","Locally Advanced Sarcoma","Metastatic Primary Malignant Central Nervous System Neoplasm","Metastatic Sarcoma","Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Prognostic Stage IIIC Breast Cancer AJCC v8","Prognostic Stage IV Breast Cancer AJCC v8","Stage IIIC Colorectal Cancer AJCC v8","Stage IVA Colorectal Cancer AJCC v8","Stage IVB Colorectal Cancer AJCC v8","Stage IVC Colorectal Cancer AJCC v8","2026-06-09",{"date":536,"type":47},{"date":634,"type":47},"2021-01-20",{"date":137,"type":21},{"name":637,"class":140},"M.D. Anderson Cancer Center",{"id":639,"slug":640,"hasResults":12,"nctId":641,"briefTitle":642,"officialTitle":643,"acronym":4,"eligibilityCriteria":644,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":645,"targetDuration":4,"studyType":22,"phases":646,"briefSummary":647,"conditions":648,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":651,"lastUpdatePostDateStruct":652,"startDateStruct":653,"completionDateStruct":655,"leadSponsor":657,"locationsCount":161},"100517314","group-cognitive-behavior-sessions-cbcsm-to-decrease-distress-in-cancer-patients-100517314","NCT06015932","Group Cognitive Behavior Sessions (CBCSM) to Decrease Distress in Cancer Patients","A Non-Randomized Translational Trial of Cognitive Behavioral Cancer Stress Management (CBCSM) and Its Effects on Cancer Distress","Inclusion Criteria:\n\n* Eligible for the cognitive behavioral cancer stress management (CBCSM) clinical service\n* Cancer diagnosis with predicted survival \\> 1 year\n* Cancer treatment within past 1 year or treatment planning in progress\n* Age \\>= 18-years\n* Moderate distress screen, indicated by Impact of Event Scale-Revised (IES-R) score \\>= 14 or clinical judgment\n* Written informed research consent\n\nExclusion Criteria:\n\n* Inability to actively participate in and learn from group therapy (e.g., psychotic symptoms, neurological condition, personality pathology) as determined by clinical judgment in clinical consultation (Individual therapy or alternative group therapy will be offered)",{"count":119,"type":21},[121],"This clinical trial tests how well cognitive behavioral cancer stress management (CBCSM) group sessions work to decrease psychological distress in cancer patients. CBCSM teaches patients how to recognize and reduce the impacts of cancer associated stress on the biological, psychological, and social life domains.",[649,650,35],"Hematopoietic and Lymphoid System Neoplasm","Malignant Solid Neoplasm","2026-06-05",{"date":631,"type":47},{"date":654,"type":47},"2017-12-20",{"date":656,"type":21},"2029-12-31",{"name":301,"class":140},{"id":659,"slug":660,"hasResults":12,"nctId":661,"briefTitle":662,"officialTitle":663,"acronym":4,"eligibilityCriteria":664,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":665,"targetDuration":4,"studyType":388,"phases":4,"briefSummary":666,"conditions":667,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":651,"lastUpdatePostDateStruct":668,"startDateStruct":669,"completionDateStruct":671,"leadSponsor":673,"locationsCount":161},"100480036","examining-blood-and-tissue-samples-to-identify-diagnostic-markers-in-patients-with-metastatic-cancer-undergoing-tumor-removal-100480036","NCT05530759","Examining Blood and Tissue Samples to Identify Diagnostic Markers in Patients With Metastatic Cancer Undergoing Tumor Removal","Integrated Genomics and Patient-Derived Cancer Models","Inclusion Criteria:\n\n* Patients (or the legally authorized representative\u002Fguardian signing on behalf of the participant) must understand and provide written informed consent prior to initiation of any study-specific procedures\n* \\>= 18 years of age\n* Patients must have a diagnosis of confirmed malignancy\n* Patient is a good medical candidate for a standard of care biopsy or surgical procedure to obtain tissue or has archival tissue available for analysis\n\nExclusion Criteria:\n\n* Uncontrolled concurrent illness including psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent\n* Inaccessible tumor for biopsy or patient does not have tumor tissue available for research use\n* Biopsy must not be considered to be more than minimal risk to the patient. Contraindications to percutaneous biopsy:\n\n  * Significant coagulopathy that cannot be adequately corrected\n  * Severely compromised cardiopulmonary function or hemodynamic instability\n  * Lack of a safe pathway to the lesion\n  * Inability of the patient to cooperate with, or to be positioned for, the procedure",{"count":611,"type":21},"This study characterizes deoxyribonucleic acid (DNA) and proteomic (protein) changes in both biopsies and tumors removed during surgery of patients who have been diagnosed with aggressive\u002Fmetastatic (that has spread to other places in the body) cancer in order to identify possible diagnostic markers and potential drugs for treating aggressive tumor types. Proteomic analyses include looking at the proteome, or all the proteins expressed, or made by DNA at a specific moment in time. Studying samples of blood, buccal (cheek), and tissue in the laboratory from patients undergoing surgical resection or biopsy may help doctors learn more about the changes that occur in the proteome, DNA alterations, and identify molecular biomarkers for which therapeutic drugs may exist. Studying the DNA in tumor tissue and in blood may also help researchers see if the tumor has important differences.",[649,35],{"date":631,"type":47},{"date":670,"type":47},"2022-06-29",{"date":672,"type":21},"2031-04-30",{"name":301,"class":140},{"id":675,"slug":676,"hasResults":12,"nctId":677,"briefTitle":678,"officialTitle":679,"acronym":4,"eligibilityCriteria":680,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":681,"targetDuration":4,"studyType":22,"phases":683,"briefSummary":684,"conditions":685,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":687,"lastUpdatePostDateStruct":688,"startDateStruct":689,"completionDateStruct":691,"leadSponsor":692,"locationsCount":439},"100407479","phase-1-testing-the-combination-of-ds-8201a-and-olaparib-in-her2-expressing-cancers-with-expansion-in-patients-with-platinum-resistant-ovarian-cancer-100407479","NCT04585958","Testing the Combination of DS-8201a and Olaparib in HER2-Expressing Cancers With Expansion in Patients With Platinum Resistant Ovarian Cancer","A Phase I Study of DS-8201a in Combination With Olaparib in HER2-Expressing Malignancies","Inclusion Criteria:\n\n* DOSE ESCALATION PHASE\n* Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\n* Patients must have HER2-positive or HER2-expressing tumors determined by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory. Specific requirement of HER2 status is outlined below:\n\n  * Dose Escalation Module 1 and Module 2:\n\n    * HER2 1-3+ expression by IHC OR\n    * HER2 amplification by next generation sequencing panel (NGS) or in situ hybridization (ISH) OR\n    * If local testing is not feasible, patients will submit archival tissue for central HER2 testing to determine eligibility. Patients with unknown or negative HER2 testing will not be eligible\n  * Dose Escalation Module 3:\n\n    * HER2 1-2+ expression by IHC OR\n    * HER2 amplification by next generation sequencing panel (NGS) or in situ hybridization (ISH) OR\n    * If local testing is not feasible, patients will submit archival tissue for central HER2 testing to determine eligibility. Patients with unknown or negative HER2 testing will not be eligible\n* DOSE EXPANSION PHASE\n* Patients must have histologically confirmed platinum resistant, high grade serous ovarian carcinoma. Platinum resistant is defined as radiographic progression \\\u003C 6 months following the last dose of platinum therapy\n* HER2 IHC 1+ per local or central testing\n* There must be least one lesion suitable for biopsy without significant risk to the patient\n* Patient disease must be evaluable or measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Biopsiable lesion cannot be the only RECIST-measurable lesion\n* DOSE ESCALATION AND DOSE EXPANSION PHASES\n* Patients must have had at least one prior line of cytotoxic chemotherapy\n* Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy\n* Patients must have archival formalin-fixed paraffin-embedded (FFPE) tissue available for central confirmation of HER2 testing\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of DS-8201a in combination with olaparib in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 1 (Karnofsky \\>= 70%)\n* Hemoglobin \\>= 10.0 g\u002FdL (within 21 days of randomization\u002Fenrollment)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n* Absolute neutrophil count \\>= 1,000\u002FmcL (within 21 days of randomization\u002Fenrollment)\n\n  * No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment\n* Platelets \\>= 100,000\u002FmcL (within 21 days of randomization\u002Fenrollment)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN), (\\\u003C 3 x ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline) (within 21 days of randomization\u002Fenrollment)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 3 x institutional ULN (within 21 days of randomization\u002Fenrollment)\n* Creatinine =\\\u003C 1.5 x institutional ULN (within 21 days of randomization\u002Fenrollment) OR\n* Glomerular filtration rate (GFR) \\>= 51 mL\u002Fmin\u002F1.73 m\\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL\u002Fmin\u002F1.73 m\\^2 (using the Cockcroft-Gault Equation) (within 21 days of randomization\u002Fenrollment)\n* Patients must have left ventricular ejection fraction (LVEF) \\>= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization\u002Fenrollment\n* Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:\n\n  * They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective\n  * They must have an undetectable viral load and a CD4 count \\>= 250 cells\u002FuL within 7 days of enrollment\n  * They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months\n  * HIV-infected patients should be monitored every 12 weeks for viral load and CD4 counts\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with brain metastases should be stable and off steroids and at least 4 weeks from radiation at the time of registration\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be better than class 2B\n* The effects of DS-8201a and olaparib on the developing human fetus are unknown. For this reason and because HER2 antibody conjugated to a topoisomerase 1 inhibitor agents as well as PARP inhibitors are known to be teratogenic; thus, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 7 months (women of childbearing potential \\[WOCBP\\] only) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of DS-8201a and olaparib administration\n* Women of non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\[FSH\\] \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method\n* Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study\n* Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration\n* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and\u002For family member available will also be eligible\n\nExclusion Criteria:\n\n* Patients who have had chemotherapy (including antibody drug therapy) within 4 weeks with the following exceptions: 1 week for weekly paclitaxel; 2 weeks or five half-lives, whichever is longer, for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents, hormonal agents; or 6 weeks for nitrosoureas or mitomycin C\n* Patients who have had radiation therapy within 4 weeks\n* Patients who have had a major surgery within 4 weeks\n* Patients who are receiving any other investigational agents\n* Patients with a history of (non-infectious) interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, has current ILD\u002Fpneumonitis, or where suspected ILD\u002Fpneumonitis cannot be ruled out by imaging at screening\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \\[COPD\\], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e. rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to DS-8201a, the inactive ingredients in the drug product, olaparib, or severe hypersensitivity to other monoclonal antibodies\n* Patients receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment\u002Finformed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* Patients with a medical history of myocardial infarction within 6 months before randomization\u002Fenrollment, symptomatic congestive heart failure (CHF) (New York Heart Association class IIb to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to randomization\n* Patients with a corrected QT interval (QTc) prolongation to \\> 470 ms (females) or \\> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)\n* Patients with multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, and other solid tumors curatively treated\n* Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\n* Patients receiving chloroquine or hydroxychloroquine will require a washout period of \\>= 14 days to be eligible for the study\n* Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade =\\\u003C 1 or baseline. Subjects with chronic grade 2 toxicities may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee (e.g., grade 2 chemotherapy-induced neuropathy)\n* Patients with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because DS-8201a is a HER2 antibody conjugated to a topoisomerase 1 inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with DS-8201a, breastfeeding should be discontinued if the mother is treated with DS-8201a. These potential risks may also apply to other agents used in this study\n* Patients who have received a live, attenuated vaccine within 30 days prior to the first dose of DS-8201a",{"count":682,"type":21},55,[24],"This phase I trial identifies the side effects and best dose of DS-8201a and olaparib in treating patients with HER2-expressing cancers that have spread to other places in the body or cannot be removed by surgery or ovarian cancer that remains despite treatment with a platinum treatment (platinum resistant). Olaparib is a drug that blocks an enzyme involved in many cell functions, including the repair of deoxyribonucleic acid (DNA) damage. Blocking this enzyme may help keep tumor cells from repairing their damaged DNA, causing them to die. DS-8201a is an antibody-drug conjugate. This agent has two components: an antibody component and a chemotherapy component. The antibody component is attached to the chemotherapy molecules. Upon administration of DS-8201a, the antibody targets and binds to tumor cells that have abundant HER2 (human-epidermal growth factor receptor 2), which is a protein on the surface of some tumor cells. The chemotherapy then enters the cells and blocks DNA replication in the tumor cells with abundant HER2, causing them to die. Giving DS-8201a and olaparib may shrink or stabilize the cancer.",[35,686,41],"Platinum-Resistant Ovarian High Grade Serous Adenocarcinoma","2026-06-04",{"date":651,"type":47},{"date":690,"type":47},"2021-05-21",{"date":137,"type":21},{"name":53,"class":54}]