[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"advanced-malignant-solid-neoplasm\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:advanced-malignant-solid-neoplasm":26},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,27,0,25,[9,54,94,114,133,152,177,220,255,279,333,355,376,398,416,463,519,545,564,588,607,627,655,675,694],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":42,"lastUpdatePostDateStruct":43,"startDateStruct":46,"completionDateStruct":48,"leadSponsor":50,"locationsCount":53},"100482618","phase-2-targeted-therapy-directed-by-genetic-testing-in-treating-patients-with-locally-advanced-or-advanced-solid-tumors-the-combomatch-screening-trial-100482618",false,"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","ALL",{"count":19,"type":20},2900,"ESTIMATED","INTERVENTIONAL",[23],"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.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40],"Advanced Malignant Solid Neoplasm","Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Locally Advanced Malignant Solid Neoplasm","Malignant Female Reproductive System Neoplasm","Metastatic HER2-Negative Breast Carcinoma","Metastatic Malignant Solid Neoplasm","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","Unresectable Malignant Solid Neoplasm","RECRUITING","2026-07-01",{"date":44,"type":45},"2026-07-02","ACTUAL",{"date":47,"type":45},"2023-04-07",{"date":49,"type":20},"2030-07-01",{"name":51,"class":52},"National Cancer Institute (NCI)","NIH",481,{"id":55,"slug":56,"hasResults":12,"nctId":57,"briefTitle":58,"officialTitle":59,"acronym":4,"eligibilityCriteria":60,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":62,"targetDuration":4,"studyType":21,"phases":64,"briefSummary":66,"conditions":67,"keywords":73,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":83,"lastUpdatePostDateStruct":84,"startDateStruct":86,"completionDateStruct":88,"leadSponsor":90,"locationsCount":93},"100414594","phase-1-a-trial-of-rsc-1255-for-treatment-of-patients-with-advanced-malignancies-100414594","NCT04678648","A Trial of RSC-1255 for Treatment of Patients With Advanced Malignancies","A Phase Ia\u002FIb, Open Label, Multi-center, Non-randomized Dose Escalation and Dose Expansion Study of RSC-1255 Alone or in Combination With Hydroxychloroquine in Patients With Advanced Solid Tumor Malignancies","Inclusion Criteria (Key Factors):\n\n1. Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:\n\n   * Participant is intolerant of existing therapy(ies) known to provide clinical benefit for their condition\n   * Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit\n   * Malignancy has progressed on standard therapy\n2. Has evaluable or measurable tumor(s) in dose-escalation by standard radiological and\u002For laboratory assessments as applicable to their malignancy.\n3. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG).\n4. Is age ≥ 18 years.\n5. Has either tissue agnostic tumors and documented RAS mutations or with glioblastoma with or without mutation in RAS\n\nExclusion Criteria (Key Factors):\n\n1. Participants receiving cancer therapy at the time of enrollment.\n2. Any clinically significant disease or condition affecting a major organ system.\n3. Significant cardiovascular disease or electrocardiogram (ECG) abnormalities.\n4. Known Gilbert's disease.\n5. Has had a previous (within 2 years) or has a current malignancy other than the target cancer.\n6. Intermittent hypokalemia\n7. Grade 1 or higher nausea, vomiting, diarrhea at baseline due to underlying disease","18 Years",{"count":63,"type":20},134,[65],"PHASE1","RSC-101 is a Phase 1a\u002F1b clinical trial of RSC-1255 in adult study participants with advanced solid tumor malignancies who are intolerant of existing therapies known to provide clinical benefit, have disease that has progressed after standard therapy, or have previously failed other therapies. The study has two phases. The purpose of Phase 1a (Dose Escalation) is to confirm the appropriate treatment dose and Phase 1b (Dose Expansion) is to characterize the safety and efficacy of RSC-1255.",[26,68,69,70,71,72],"RAS Mutation","Lung Cancer","Colon Cancer","Glioblastoma","Pancreatic Cancer",[74,75,76,77,78,79,71,80,81,82],"Malignancy","Cancer","Refractory","RAS mutation","Lung","Colon","RSC-1255","Progression","Pancreatic","2026-06-22",{"date":85,"type":45},"2026-06-23",{"date":87,"type":45},"2021-03-03",{"date":89,"type":20},"2027-01-30",{"name":91,"class":92},"RasCal Therapeutics, Inc.","INDUSTRY",3,{"id":95,"slug":96,"hasResults":12,"nctId":97,"briefTitle":98,"officialTitle":99,"acronym":4,"eligibilityCriteria":100,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":101,"targetDuration":4,"studyType":21,"phases":103,"briefSummary":104,"conditions":105,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":106,"lastUpdatePostDateStruct":107,"startDateStruct":109,"completionDateStruct":111,"leadSponsor":113,"locationsCount":5},"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":102,"type":20},500,[23],"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.",[26,32],"2026-06-16",{"date":108,"type":45},"2026-06-17",{"date":110,"type":45},"2025-03-18",{"date":112,"type":20},"2028-03-31",{"name":51,"class":52},{"id":115,"slug":116,"hasResults":12,"nctId":117,"briefTitle":118,"officialTitle":119,"acronym":4,"eligibilityCriteria":120,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":121,"targetDuration":4,"studyType":21,"phases":123,"briefSummary":124,"conditions":125,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":106,"lastUpdatePostDateStruct":126,"startDateStruct":127,"completionDateStruct":129,"leadSponsor":131,"locationsCount":132},"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":122,"type":20},66,[65],"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.",[26,32,40],{"date":108,"type":45},{"date":128,"type":45},"2024-06-07",{"date":130,"type":20},"2026-08-31",{"name":51,"class":52},6,{"id":134,"slug":135,"hasResults":12,"nctId":136,"briefTitle":137,"officialTitle":138,"acronym":4,"eligibilityCriteria":139,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":140,"targetDuration":4,"studyType":21,"phases":142,"briefSummary":143,"conditions":144,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":106,"lastUpdatePostDateStruct":145,"startDateStruct":146,"completionDateStruct":148,"leadSponsor":150,"locationsCount":151},"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":141,"type":20},88,[23],"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.",[26,32,40],{"date":108,"type":45},{"date":147,"type":45},"2022-11-14",{"date":149,"type":20},"2027-12-31",{"name":51,"class":52},36,{"id":153,"slug":154,"hasResults":12,"nctId":155,"briefTitle":156,"officialTitle":157,"acronym":4,"eligibilityCriteria":158,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":159,"targetDuration":4,"studyType":21,"phases":161,"briefSummary":162,"conditions":163,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":169,"lastUpdatePostDateStruct":170,"startDateStruct":171,"completionDateStruct":173,"leadSponsor":175,"locationsCount":176},"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":160,"type":20},42,[65,23],"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.",[26,164,165,32,166,167,168],"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":106,"type":45},{"date":172,"type":45},"2023-09-28",{"date":174,"type":20},"2027-03-01",{"name":51,"class":52},23,{"id":178,"slug":179,"hasResults":12,"nctId":180,"briefTitle":181,"officialTitle":182,"acronym":4,"eligibilityCriteria":183,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":184,"targetDuration":4,"studyType":21,"phases":186,"briefSummary":188,"conditions":189,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":210,"startDateStruct":212,"completionDateStruct":214,"leadSponsor":216,"locationsCount":219},"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":185,"type":20},160,[187],"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.",[190,191,192,193,26,194,195,196,197,198,199,32,200,201,202,203,204,205,206,207,208],"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","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Melanoma","Metastatic Renal Cell Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","2026-06-10",{"date":211,"type":45},"2026-06-12",{"date":213,"type":45},"2026-06-08",{"date":215,"type":20},"2028-12-31",{"name":217,"class":218},"OHSU Knight Cancer Institute","OTHER",1,{"id":221,"slug":222,"hasResults":12,"nctId":223,"briefTitle":224,"officialTitle":224,"acronym":4,"eligibilityCriteria":225,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":226,"targetDuration":4,"studyType":21,"phases":228,"briefSummary":229,"conditions":230,"keywords":243,"overallStatus":247,"whyStopped":4,"lastUpdateSubmitDate":248,"lastUpdatePostDateStruct":249,"startDateStruct":250,"completionDateStruct":252,"leadSponsor":253,"locationsCount":4},"100643697","phase-2-exploratory-study-on-the-efficacy-and-safety-of-trastuzumab-rezetecan-in-the-treatment-of-her2-expressiong-advanced-solid-tumor-100643697","NCT07631884","Exploratory Study on the Efficacy and Safety of Trastuzumab Rezetecan in the Treatment of HER2-Expressiong Advanced Solid Tumor","Inclusion Criteria:\n\n1. Male and female participants aged 18 years or older.\n2. Participants with locally advanced, unresectable or metastatic solid tumors who have progressed after at least one prior systemic therapy for advanced\u002Fmetastatic disease, or have no satisfactory alternative treatment options. Eligible tumor types include but are not limited to biliary tract cancer, endometrial cancer, urothelial carcinoma, pancreatic cancer, colorectal cancer, gastric cancer, non-small cell lung cancer, head and neck adenocarcinoma (salivary gland adenocarcinoma, lacrimal gland adenocarcinoma, adenocarcinoma of unknown primary in the neck), cervical cancer, ovarian cancer and adenocarcinoma of unknown primary. Breast cancer is excluded.\n3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.\n4. Confirmed HER2 expression defined as IHC 1+, 2+ or 3+ (per GC criteria).\n5. Willing and able to provide adequate tumor specimens for central pathological re-testing of HER2 status. For participants previously treated with anti-HER2 therapy, tumor specimens obtained after the last anti-HER2 treatment are optional.\n6. At least one measurable lesion at baseline per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.\n7. Adequate organ and bone marrow function within 14 days prior to enrollment, meeting the following criteria:\n\n   Hemoglobin ≥ 9 g\u002FdL; Platelet count ≥ 100,000\u002Fmm³; Absolute neutrophil count (ANC) ≥ 1500\u002Fmm³; Serum albumin ≥ 3.0 g\u002FdL; Prothrombin time (PT), activated partial thromboplastin time (aPTT) and International Normalized Ratio (INR) ≤ 1.5 × upper limit of normal (ULN); Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN; ≤ 5 × ULN for participants with liver metastases; Total bilirubin ≤ 1.5 × ULN for participants without liver metastases; ≤ 3 × ULN for participants with Gilbert's syndrome or liver metastases at baseline; Creatinine clearance ≥ 30 mL\u002Fmin (calculated by the Cockcroft-Gault formula)\n8. Left ventricular ejection fraction (LVEF) ≥ 50% assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days prior to enrollment.\n\nExclusion Criteria:\n\nParticipants meeting any of the following conditions are ineligible for this study:\n\n1. Presence of any severe and\u002For uncontrolled diseases:\n\n   * Poorly controlled blood pressure (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg); poorly controlled diabetes (fasting blood glucose \\[FBG\\] \\> 10 mmol\u002FL).\n   * Grade ≥ 2 myocardial ischemia, myocardial infarction, arrhythmia (QTc interval ≥ 470 ms), or Grade ≥ 2 congestive heart failure (per New York Heart Association \\[NYHA\\] classification).\n   * Active or uncontrolled severe infections (Grade ≥ 2 per NCI CTCAE) requiring systemic antibacterial, antifungal or antiviral therapy, including pulmonary tuberculosis.\n   * History of active tuberculosis.\n   * Uncontrolled ascites, pericardial effusion or pleural effusion requiring repeated drainage.\n2. Active hepatitis: Liver function not meeting the inclusion criteria. Hepatitis B: HBV DNA ≥ 2000 IU\u002FmL or ≥ 10\\^4 copies\u002FmL.Hepatitis C: HCV RNA ≥ 2000 IU\u002FmL or ≥ 10\\^4 copies\u002FmL. Participants with viral load below the above thresholds after nucleoside antiviral therapy are eligible. Chronic hepatitis B virus carriers with HBV DNA \\\u003C 10\\^4 IU\u002FmL must receive concurrent antiviral treatment throughout the study for enrollment.\n3. History of immunodeficiency diseases, including HIV positivity or other acquired\u002Fcongenital immunodeficiency disorders.\n4. History of allogeneic solid organ transplantation or allogeneic hematopoietic stem cell transplantation.\n5. Confirmed meningeal metastasis, spinal cord metastasis or spinal cord compression.\n6. Within 6 months prior to the first study drug administration, presence of esophageal gastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, acute gastrointestinal bleeding, extensive intestinal resection (partial colectomy or extensive small bowel resection complicated with chronic diarrhea), Crohn's disease, ulcerative colitis or long-standing chronic diarrhea.\n7. Unhealed or poorly healing wounds, or active ulcers.\n8. Toxicities from prior anti-tumor therapy have not resolved to Grade 0 or 1 per NCI CTCAE version 5.0.\n9. Received major surgery, incisional biopsy or significant traumatic injury within 28 days before study treatment initiation; or with long-standing unhealed wounds or fractures.\n10. History of severe hypersensitivity reactions to monoclonal antibodies; known allergy to the active ingredients or excipients of the study drug.",{"count":227,"type":20},15,[23],"The goal of this clinical trial is to learn if Trastuzumab Rezetecan can treat advanced solid tumors with HER-2 expression in adult participants.\n\nThe main question it aims to answer is: What is the objective response rate of Trastuzumab Rezetecan in adult patients with HER-2 expressed advanced solid tumors? Participants will receive intravenous infusion of Trastuzumab Rezetecan on Day 1 of each 21-day treatment cycle. The dosage is 4.8 mg\u002Fkg per cycle; participants with a body weight of 85 kg or above will receive a fixed dose of 408 mg every 3 weeks.",[231,232,26,29,40,32,233,234,235,236,237,238,239,240,241,242],"Solid Tumors","Neoplasms (Cancer \u002F Tumors)","HER2 Expression","Biliary Tract Neoplasms","Endometrial Neoplasms","Urothelial Carcinoma (UC)","Pancreatic Neoplasms","Colorectal Neoplasms","Gastric Neoplasms","Non-Small Cell Lung Carcinoma (NSCLC)","Head and Neck Neoplasms","Cervical Neoplasms",[244,245,246],"HER2 expression","Trastuzumab Rezetecan","Advanced Solid Tumor","NOT_YET_RECRUITING","2026-06-02",{"date":213,"type":45},{"date":251,"type":20},"2026-06-15",{"date":215,"type":20},{"name":254,"class":218},"Haihua Yuan",{"id":256,"slug":257,"hasResults":12,"nctId":258,"briefTitle":259,"officialTitle":260,"acronym":4,"eligibilityCriteria":261,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":262,"targetDuration":4,"studyType":21,"phases":263,"briefSummary":264,"conditions":265,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":269,"lastUpdatePostDateStruct":270,"startDateStruct":272,"completionDateStruct":274,"leadSponsor":276,"locationsCount":278},"100500068","phase-1-au409-for-the-treatment-of-advanced-primary-liver-cancers-or-solid-tumor-with-liver-metastatic-disease-100500068","NCT05791448","AU409 for the Treatment of Advanced Primary Liver Cancers or Solid Tumor With Liver Metastatic Disease","First in Human Dose Escalation Study of AU409 in Patients With Advanced Primary Liver Cancers or Advanced Solid Tumor With Liver Predominant Metastatic Disease","Inclusion Criteria:\n\n* Age \\>= 18 years old\n* Patients must have histopathologically \u002Fcytologically confirmed advanced solid tumor, which is refractory to standard therapeutic options, or for which there are no standard therapeutic options. Failure of all approved therapies that have a marginal impact on survival is not required as long as the treating physician considers that treatment on study is appropriate for the subject and documents that the subject elects to defer the approved therapies\n* During the dose-escalation portion, patients must have primary liver malignancy (including hepatocellular carcinoma or cholangiocarcinoma) OR a solid tumor with liver dominant disease; liver dominant disease is defined as the majority of the tumor burden being in the liver per investigator assessment AND no more than two extrahepatic sites of disease (site of disease refers to organ or system). During the dose expansion portion of the study, eligibility may be limited to one or more tumor types depending on findings from the dose-escalation phase; this will be clarified in an amendment\n* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Patient must have recovered from any toxic effects of previous chemotherapy, targeted therapy or radiotherapy as judged by the Investigator to =\\\u003C grade 1 (except for alopecia). Residual sensory neuropathy =\\\u003C grade 2 is allowed. Residual endocrine adverse events (such as hypothyroidism or hypoadrenalism) that are manageable with replacement therapy are allowed\n* Previous chemotherapy\u002Fradiotherapy\u002Ftargeted\u002Fimmunotherapy therapy should have been completed at least 4 weeks prior to start of AU409 administration, or five half-lives, whichever is shorter (except for palliative radiation therapy that should be completed \\>= 14 days prior to study entry)\n* Patients must have an estimated life expectancy of at least 3 months\n* Women of child-bearing potential (WOCBP) 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. A male participant must agree to use highly effective contraception during the intervention period and for 60 days after the last dose of AU409 and refrain from donating sperm during this period. WOCBP are eligible to participate if they are not pregnant, not breastfeeding, and agree to follow the contraceptive guidance during the study intervention period and for at least 90 days after the last dose of AU409\n\n  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately\n* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)\n* Patients must agree, as part of the informed consent, to undergo liver biopsy (for a subset of patients enrolled at and above dose level 4) and to provide blood for pharmacokinetics analysis\n* Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3\n* Platelet count \\>= 100,000\u002Fmm\\^3\n* Hemoglobin \\>= 8 g\u002FdL (prior transfusion is allowed if completed 2 weeks prior to screening and hemoglobin remains \\>= 8 g\u002FdL)\n* For patients with HCC with splenic sequestration: ANC \\>= 1000\u002Fmm\\^3\n* For patients with HCC with splenic sequestration: Platelets \\>= 70,000\n* Calculated clearance \\>= 60 mL\u002Fmin\u002F1.73 m\\^2. Actual body weight should be used for calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For subjects with a Body Mass Index (BMI) \\> 30 kg\u002Fm\\^2, lean body weight should be used instead\n* Total bilirubin =\\\u003C 1.5 X upper limit of normal (ULN) (subjects with known Gilbert's hepatic function disease can have bilirubin of up to 2 X ULN)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 3 X ULN; or AST\u002FALT =\\\u003C 5 X ULN if patient has liver tumors\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) =\\\u003C 1.8 times upper limit of normal (unless patient is on anticoagulation)\n\nExclusion Criteria:\n\n* Patients who have had hypersensitivity to pentamidine or any excipients of AU409\n* Treatment with other anticancer therapies (including surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation therapy, etc.) or investigational therapy within 28 days prior to study entry (except for palliative radiation therapy that should be completed \\>= 14 days prior to study entry)\n* Hepatocellular carcinoma patients with a Child Pugh score \\>= B7\n* Patients with known central nervous system metastases which are untreated or symptomatic; patients with treated brain metastases (completed \\>= 30 days prior to screening) are allowed provided they are asymptomatic and are off steroids\n* Patient with a history of the following within 6 months prior to cycle 1 day 1: a myocardial infarction, severe\u002Funstable angina pectoris, coronary\u002Fperipheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia, cerebrovascular accident, transient ischemic attack, or seizure disorder. Atrial fibrillation is allowed if rate is controlled\n* Patients who have corrected QT (QTc) interval to \\> 470 msec (Fredericia's equation) on 2 out of 3 electrocardiogram (ECG)'s (if first ECG has QTc \\\u003C 470, no need to repeat, if first ECG has QTc \\> 470 repeat twice for a total of 3 ECG's)\n* Patients who are on therapeutic anticoagulation with warfarin; however, patients on therapeutic doses of with low molecular weight heparins or Factor Xa inhibitors are eligible\n* Patient with history of gastrointestinal surgery or malabsorptive conditions that may change the absorption of drugs and\u002For cause rapid transit (such as total gastrectomy, small bowel resection, etc.)\n* Patients who have known active hepatitis B. Patients with chronic hepatitis B who are on anti-viral therapy and have a hepatitis B viral load of =\\\u003C 500 IU\u002FmL are allowed on the study. Patients with chronic Hepatitis C are allowed\n* Patients who have active infection requiring treatment (except hepatitis B and C as noted above) including known human immunodeficiency virus (HIV) infection\n* Patients who have concurrent conditions resulting in immune compromise, including chronic treatment with corticosteroids or other immunosuppressive agents\n* Patients who have any other condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results\n* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants\n* Patients who are on medications that are considered to be strong inducers or inhibitors of the cytochrome P450 isoenzymes should have such medications discontinued or replaced. Such medications should be avoided for one week prior to first dose of treatment and during the trial participation. If these medications are absolutely necessary for the patient and cannot be replaced, enrollment may still be considered on a case by case basis if it is in the patient's best interest and after discussion with the principal investigator (PI)",{"count":151,"type":20},[65],"This phase I trial tests the safety, side effects, and best dose of a new intervention, AU409, in treating patients with primary liver cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or advanced solid tumors that have spread to the liver (liver metastatic disease). AU409 may stop cancer from growing and spreading. This trial may help researchers determine if AU409 is safe and effective in treating patients with liver cancers and solid tumors with liver metastatic disease.",[266,192,26,267,268,203,206],"Advanced Cholangiocarcinoma","Metastatic Malignant Neoplasm in the Liver","Refractory Malignant Solid Neoplasm","2026-05-29",{"date":271,"type":45},"2026-06-01",{"date":273,"type":45},"2023-03-29",{"date":275,"type":20},"2028-03-29",{"name":277,"class":218},"University of Southern California",2,{"id":280,"slug":281,"hasResults":12,"nctId":282,"briefTitle":283,"officialTitle":284,"acronym":4,"eligibilityCriteria":285,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":286,"targetDuration":4,"studyType":21,"phases":288,"briefSummary":289,"conditions":290,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":269,"lastUpdatePostDateStruct":326,"startDateStruct":327,"completionDateStruct":329,"leadSponsor":331,"locationsCount":219},"100442316","phase-1-iacs-6274-with-or-without-bevacizumab-and-paclitaxel-for-the-treatment-of-advanced-solid-tumors-100442316","NCT05039801","IACS-6274 With or Without Bevacizumab and Paclitaxel for the Treatment of Advanced Solid Tumors","A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-Tumor Activity of IACS-6274 as Monotherapy and in Combination in Patients With Advanced Solid Tumors","Inclusion Criteria All Parts\n\n1. Provision of written informed consent prior to any study related procedures and compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.\n2. Male or female patients ≥18 years of age at the time of study entry who agree to participate by giving written informed consent prior to participation in any study related activities.\n3. Histologically or cytologically confirmed advanced solid tumors, specifically:\n\n   Dose Escalation for Part A may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2\u002FSTK11\u002FNF1 mutations Patients with low ASNS expression levels (HGSOC or endometrial cancer) Patients who had immunotherapy (IO) melanoma (Minimum treatment duration of prior PD-1 or PD-L1-containing regimen of 12 weeks \\[or equivalent of 2 response evaluations\\]).\n\n   Patients with post-platinum HNSCC Patients with chondrosarcoma Patients with ARID1A mutant clear cell ovarian cancer\n\n   Dose Escalation for Part B may include:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer that is platinum-resistant, defined as disease relapse within a platinum-free interval (PFI, or the time elapsed from the last date of platinum dose until PD) of \\\u003C 6 months, and with less than 5 prior therapies\n\n   Dose Expansion for Part B limited to:\n\n   Confirmed recurrent high-grade non-mucinous ovarian cancer with low ASNS expression levels that is platinum-resistant, defined as disease relapse within a PFI of \\\u003C 6 months, and with less than 5 prior therapies.\n\n   Dose Escalation for Part C may include:\n\n   Patients with tumors harboring actionable KEAP1\u002FNFE2L2 mutations Patients with tumors harboring PIK3CA hotspot mutations, activating AKT mutations, and inactivating PTEN mutations (irrespective of KEAP1\u002FNFE2L2 mutations) Patients with low ASNS expression levels (HGSOC)\n\n   Dose Expansion for Part C limited to:\n\n   Patients with NSCLC with actionable KEAP1\u002FNFE2L2 mutations Patients with HGSOClow ASNS expression levels (irrespective of biomarker status for KEAP1\u002FNFE2L2)\n4. Patients must have received at least one line of therapy for advanced stage disease and be refractory or ineligible to available existing therapy(ies) known to provide clinical benefit for their condition.\n5. Prior treatment with chemotherapy, radiotherapy, immunotherapy or any investigational therapies must have been completed at least 3 weeks or at least five half lives, whichever is shorter, before the study drug administration, and all AEs (excluding alopecia and peripheral neuropathy) have either returned to ≤Grade 1 or stabilized. Patients with concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) are allowed.\n6. Fresh and\u002For archival tumor tissue from a biopsy obtained between the completion of the most recent line of treatment until study entry must be available for mutation and biomarker analysis. If available, archival tumor tissue from the time of initial diagnosis or the most recent biopsy (archival and\u002For fresh) will be collected. For ovarian cancer patients, a fresh biopsy must be collected in addition to archival tumor tissue. NOTE: No fresh tumor tissue will be required if a previous biopsy detected the selected mutations for each cohort. In all cases, procedures to obtain fresh tumor tissue should not put the patient at undue risk, and should only be performed if the risk is minimal (no greater than 2% risk of serious or severe complications).\n7. Patients must have at least 1 lesion (measurable and\u002For non-measurable) that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessments.\n8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.\n9. Adequate organ function as indicated by the following laboratory values:\n\n   Absolute neutrophil count (ANC) ≥1.0×109\u002FL Platelets ≥100×109\u002FL Hemoglobin ≥9.0 g\u002FdL (\\>5.59 mmol\u002FL) Creatinine clearance (CrCl) \\>50 mL\u002Fmin. Actual body weight should be used for calculating creatinine clearance using the Cockroft Gault equation (except for patients with body mass index \\>30 kg\u002Fm2 when the lean body weight should be used, and without the need for chronic dialysis therapy).\n\n   Serum total bilirubin ≤1.5×ULN (with the exception of patients with known thalassemia minor mutations or Gilbert's syndrome: serum total bilirubin must be \\\u003C3×ULN in these patients) Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤2.5×ULN or ≤5×ULN for patients with liver metastases)\n10. Adequate cardiac function with a left ventricular ejection fraction ≥50%\n11. Female patients of non childbearing potential, who are physiologically incapable of becoming pregnant, are eligible to enter and participate in the study if they:\n\n    have had a hysterectomy, OR have had a bilateral oophorectomy, OR have had a bilateral salpingectomy, OR is postmenopausal (total cessation of menses for ≥2 years, or follicle stimulating hormone ≥50 IU\u002FL).\n12. Female patients of childbearing potential, who are not post-menopausal or surgically sterile and intent to be sexually active with a non-sterile male partner, are required to use one form of highly effective contraception combined with a barrier method (male condom, female condom, cervical cap, diaphragm with spermicide, or contraceptive sponge with spermicide) of contraception starting before entering the study and until 4 weeks after the last dose of treatment.\n\n    Highly effective non-hormonal contraceptive methods that are acceptable include:\n\n    Total\u002Ftrue abstinence\\*\\*\\* for the total duration of the study treatment and for at least 1 month after the last dose of study treatment. Periodic abstinence using methods such as calendar ovulation, symptothermal, post ovulation methods, declaration of abstinence solely for the duration of a trial, or withdrawal are not acceptable methods of contraception.\n\n    Having a vasectomized sexual partner, who received post-vasectomy confirmation of azoospermia, combined with a barrier method as described above.\n\n    Bilateral tubal occlusion combined with a barrier method as described above. Intrauterine device with copper banded coils, combined with a barrier method as described above.\n\n    Highly effective hormonal contraceptive methods that are acceptable include:\n\n    Combined oral pill contraception (normal and low-dose oral pills, or progesterone-based oral pills using desogestrel) combined with a barrier method as described above. NOTE: cerazette is currently the only highly efficacious progesterone-based pill available.\n\n    Injection (e.g., medroxyprogesterone) combined with a barrier method as described above.\n\n    Patch (e.g., norelgestromin or ethinyl estradiol transdermal system) combined with a barrier method as described above.\n\n    Implants (etonorgestrel-releasing) combined with a barrier method as described above.\n\n    Intravaginal device (e.g., ethinyl estradiol- or etonogestrel-releasing) combined with a barrier method as described above.\n\n    Intrauterine system (levonorgestrel-releasing) combined with a barrier method as described above.\n\n    In addition to the to use one form of highly effective contraception combined with a barrier method, female patients of childbearing potential must have a negative serum pregnancy test at screening (within 7 days of the start of treatment) and must not be breastfeeding.\n13. Non-sterile men, who are not sexually abstinent and intend to be sexually active with a woman of childbearing potential, must use a condom from the start of the trial and until 16 weeks after the last dose of treatment, or must practice total abstinence\\*\\*\\* for the total duration of the study treatment and at least 3 months after the last dose of study treatment. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female partners of childbearing potential should consider the use of at least one contraception method describe above. If the female partner is pregnant, male participants should use a condom plus spermicide.\n\n    * Total\u002Ftrue abstinence is defined as a patient who refrains from any form of sexual intercourse, and this is in line with their usual and\u002For preferred lifestyle.\n\nExclusion Criteria All Parts\n\n1. Prior malignancy within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, or carcinoma in situ of the cervix, breast or bladder.\n2. Known primary central malignancy or symptomatic central nervous system metastasis(es).\n\n   Note: Patients with stable, previously treated brain metastases may participate if neurologic symptoms have resolved, patients have been off steroids (at least 7 days for Part A and Part B, and at least 4 weeks for Part C), and there is no evidence of disease progression by imaging for at least 2 weeks before the first dose of study treatment.\n3. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following cardiac conditions:\n\n   1. Any unstable cardiac arrhythmia within 6 months prior to enrolment\n   2. Prolongation of the Fridericia corrected QT (QTcF) interval defined as \\>450 ms for males and \\>470 ms for females\n   3. History of any of the following cardiovascular conditions within 6 months of enrolment:\n\n      * cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.\n4. Major surgical intervention within 28 days before study drug administration, or an anticipated need for major surgery during the study.\n5. Significant acute or chronic infections.\n6. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.\n7. Treatment with strong cytochrome P450 subtype 3A4 (CYP3A4) inducers and inhibitors (including grapefruit juice) within 2 weeks of the first dose of study drug NOTE: patients must have stopped taking St. John's Wort 3 weeks prior to the start of treatment and stopped taking enzalutamide 4 weeks prior to the start of treatment.\n8. Treatment with strong CYP450 subtype 2D6 (CYP2D6) inhibitors or sensitive CYP3A4 substrates within 7 days of the first dose of study drug.\n9. Radiotherapy within 4 weeks prior to the start of study drug. Palliative radiotherapy for symptomatic control is acceptable if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned.\n10. Underlying medical conditions (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases), for which in the investigator's opinion will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or AEs.\n11. History of allergic reactions attributed to compounds of similar chemical or biological composition to any of the compounds in the study.\n12. Known history of alcohol or drug abuse.\n13. Legal incapacity or limited legal capacity.\n14. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation. Patients should not have gastrointestinal illnesses (such as refractory nausea and vomiting, chronic gastrointestinal disease or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretionof IACS-6274 and capivasertib, which are oral agents.\n15. Patients unwilling to comply with protocol requirements related to the assigned part.\n16. Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.\n\nPart B Specific Exclusion Criteria (B1) Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, three or more features of partially controlled asthma).\n\n(B2) Patient has a known hypersensitivity to paclitaxel or bevacizumab components or excipients.\n\n(B3) Patient has a history of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.\n\n(B4) Patient has proteinuria as demonstrated by urine protein:creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate \\\u003C2 g of protein in 24 hours to be eligible).\n\n(B5) Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).\n\n(B6) Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. (B7) Patient has pre-existing peripheral neuropathy that is Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.\n\n(B8) Patient requires paracentesis 2 weeks prior to trial enrolment. Part C Specific Exclusion Criteria (C1) History of another primary malignancy, except for a malignancy treated with curative intent, with no known active disease ≥5 years before the first dose of treatment, with low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.\n\n(C2) Patient has a known hypersensitivity to capivasertib components or any excipients of the product.\n\n(C3) Clinically significant abnormalities of glucose metabolism as defined by any of the following: Diagnosis of diabetes mellitus type I or II (irrespective of management), Glycosylated haemoglobin (HbA1c) \\>8% (64 mmol\u002Fmol) (C4) Patients with evidence of severe or uncontrolled systemic liver disease including severe hepatic impairment, or abnormal liver enzymes at screening (AST or ALT \\>2.5 x ULN; total bilirubin \\>1.5 x ULN).\n\n(C5) Patients with elevated alkaline phosphatase (ALP) can be enrolled if the abnormal value is due to the presence of bone metastasis, but liver function is considered adequate according to the principal investigator.\n\n(C6) Patients with persistent toxicities (Grade ≥2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included after consultation with the sponsor and the study physician.\n\n(C7) Patients with spinal cord compression or leptomeningeal disease not requiring steroids for at least 4 weeks prior to start of study intervention.\n\n(C8) Patients with clinically significant cardiovascular disease including, but not limited to, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident \\[CVA\\]) within 6 months of enrollment. In addition, patients will be excluded based on the study physician's judgment of the following criteria:\n\n* Mean resting corrected QT interval \\>470ms, obtained from triplicate ECGs performed at screening.\n* Medical history significant for arrhythmia that is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation regardless of treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be included based on the study physician's judgment.\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia of Grade ≥1, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relative, history of QT prolongation associated with other medications that required discontinuation of the medication.\n* Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association Grade ≥2.\n* Uncontrolled hypotension: SBP \\\u003C90 mmHg and\u002For DBP \\\u003C50 mmHg.\n* Cardiac ejection fraction outside institutional range of normal or \\\u003C50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \\[MUGA\\] scan if an echocardiogram cannot be performed or is inconclusive).\n\n(C9) Patients with active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice) are excluded.\n\n(C10) Patients with active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening are excluded.\n\nHuman immunodeficiency virus (HIV) positive patients with a viral load \\> 400 copies\u002FmL and a CD4+ T-cell count of \\\u003C350 cells\u002FuL or with a history of an acquired immunodeficiency syndrome (AIDS) opportunistic infection within the past 12 months are excluded. Patients with a higher viral load or lower CD4+ count (\\\u003C 350 cells\u002FuL) may be considered for eligibility if the patient has a potentially curable malignancy or for interventions in a later stage of development that have demonstrated prior activity with a given cancer.\n\nHIV-positive patients receiving antiretroviral therapies should be on established ART for at least four weeks before starting treatment to ensure that treatment is tolerated and that toxicities are not confused with investigational drug toxicities. HIV-positive patients receiving antiretroviral therapies that are strong CYP3A4\u002F5 inhibitors\u002F inducers or sensitive substrates of CYP3A4 will be excluded due to the potential for drug-drug interaction with capivasertib.\n\n(C12) Patients who are undergoing any concurrent anticancer treatment or any concomitant medication that may interfere with the study drugs according to local clinical guidelines are excluded.\n\n(C13) Patients who received palliative radiotherapy within 2 weeks prior to the start of study treatment; or radiotherapy to more than 30% of the bone marrow within 4 weeks before the start of study treatment are excluded.",{"count":287,"type":20},54,[65],"To find the highest tolerable dose of IACS-6274 that can be given alone, in combination with bevacizumab and paclitaxel, or in combination with capivasertib to patients who have solid tumors. The safety and tolerability of the study drug(s) will also be studied.",[291,191,26,194,292,293,294,295,296,297,298,299,300,301,302,303,304,305,306,307,308,309,310,311,312,313,314,315,316,317,318,319,320,321,322,323,324,325],"Advanced Endometrial Carcinoma","Advanced Ovarian Clear Cell Adenocarcinoma","Chondrosarcoma","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Pathologic Stage III Cutaneous Melanoma AJCC v8","Pathologic Stage IIIA Cutaneous Melanoma AJCC v8","Pathologic Stage IIIB Cutaneous Melanoma AJCC v8","Pathologic Stage IIIC Cutaneous Melanoma AJCC v8","Pathologic Stage IIID Cutaneous Melanoma AJCC v8","Pathologic Stage IV Cutaneous Melanoma AJCC v8","Recurrent Ovarian High Grade Serous Adenocarcinoma","Refractory Endometrial Carcinoma","Refractory Head and Neck Squamous Cell Carcinoma","Refractory Melanoma","Refractory Ovarian Clear Cell Adenocarcinoma","Refractory Ovarian High Grade Serous Adenocarcinoma","Stage III Ovarian Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Ovarian 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 Ovarian Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8",{"date":271,"type":45},{"date":328,"type":45},"2021-09-30",{"date":330,"type":20},"2028-06-30",{"name":332,"class":218},"M.D. Anderson Cancer Center",{"id":334,"slug":335,"hasResults":12,"nctId":336,"briefTitle":337,"officialTitle":338,"acronym":4,"eligibilityCriteria":339,"healthyVolunteers":340,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":341,"targetDuration":4,"studyType":21,"phases":343,"briefSummary":345,"conditions":346,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":347,"lastUpdatePostDateStruct":348,"startDateStruct":349,"completionDateStruct":351,"leadSponsor":353,"locationsCount":93},"100603814","telephone-based-coaching-sessions-tac-to-improve-advance-care-planning-participation-in-advanced-cancer-patients-and-their-support-person-100603814","NCT07141407","Telephone-Based Coaching Sessions (TAC) to Improve Advance Care Planning Participation in Advanced Cancer Patients and Their Support Person","Community-Engaged Pilot Testing of Talking About Cancer (TAC) to Improve Engagement in Advance Care Planning","Inclusion Criteria:\n\n* PATIENT: Current diagnosis of stage III or IV cancer\n* PATIENT: Able to provide informed consent\n* PATIENT: Fluent in English or Spanish\n* PATIENT: Have access to a telephone, computer, or mobile device\n* CAREGIVER (SUPPORT PERSON): Person patient indicates provides support\n* CAREGIVER (SUPPORT PERSON): English or Spanish speaking\n* CAREGIVER (SUPPORT PERSON): 18 years of age or older\n* CAREGIVER (SUPPORT PERSON): Able to provide informed consent\n\nExclusion Criteria:\n\n* PATIENT: Too ill or weak to complete the interviews (as judged by the interviewer)\n* PATIENT: Receiving hospice at the time of enrollment\n* PATIENT: Younger than age 18",true,{"count":342,"type":20},80,[344],"NA","This clinical trial studies whether telephone-based coaching sessions, Talking About Cancer (TAC), work to improve engagement in advance care planning (ACP) 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 their support person. Participation in ACP, which includes having end of life (EOL) care conversations and completing advance directives (e.g., living will, health care proxy, do not resuscitate order), improves quality EOL care. Despite this, less than half of patients with advanced cancer have EOL care conversations or complete advance directives. TAC coaching sessions are delivered by a social worker over the phone. They are designed to help patients and their support person communicate about ACP, manage the distress these conversations can cause, and participate in the process of ACP with a clear action plan of having goals-of-care conversations and completing advance directives. This may be an effective way to improve ACP participation in advanced cancer patients and their support person.",[26,165],"2026-05-27",{"date":269,"type":45},{"date":350,"type":45},"2026-04-08",{"date":352,"type":20},"2026-12-14",{"name":354,"class":218},"Fred Hutchinson Cancer Center",{"id":356,"slug":357,"hasResults":12,"nctId":358,"briefTitle":359,"officialTitle":360,"acronym":4,"eligibilityCriteria":361,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":362,"targetDuration":4,"studyType":21,"phases":364,"briefSummary":365,"conditions":366,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":367,"lastUpdatePostDateStruct":368,"startDateStruct":370,"completionDateStruct":372,"leadSponsor":374,"locationsCount":219},"100549787","fasting-mimicking-diet-for-reducing-immune-related-adverse-events-for-cancer-patients-on-immune-checkpoint-inhibitors-fmd-ici-trial-100549787","NCT06438588","Fasting Mimicking Diet for Reducing Immune Related Adverse Events for Cancer Patients on Immune Checkpoint Inhibitors, FMD-ICI Trial","Effect of Fasting Mimicking Diet (FMD) on Immune Related Adverse Events for Cancer Patients on Immune Checkpoint Inhibitors: The FMD-ICI Feasibility Pilot Study","Inclusion Criteria:\n\n* Patients undergoing immunotherapy regardless of prior immunotherapy history\n* Age ≥ 18 years\n* Body mass index (BMI) \\> 19\n* Histological confirmation of advanced staged malignancies (stage 3 or 4) appropriate for the following types of immunotherapy: PD-1 Antibody (nivolumab, pembrolizumab), PD-L1 Antibody (atezolizumab, avelumab, durvalumab), CTLA-4 Antibody (ipilimumab) or any combination thereof\n\nExclusion Criteria:\n\n* Age \\\u003C 18 years\n* Pregnant women\n* Nursing mothers\n* Persons of childbearing potential who are unwilling to employ adequate contraception\n* Patients will be excluded if they are on insulin due to diabetes \\[diabetic patients will be asked to monitor their glucose levels with a continuous glucose monitoring (CGM) device\\], if they have allergies to any of the components in the FMD, if there is unacceptable deterioration of their nutritional status and cancer progression",{"count":363,"type":20},10,[344],"This clinical trial assesses an effective and translatable care model to understand and reduce the adverse effects that cancer patients experience during their treatment therapies and thereby enhance their well-being and quality of life. Excessive immune activation can affect multiple organs with the most common adverse effects being skin rash, diarrhea, colitis, fatigue, hypothyroidism and anorexia. A restrictive calorie diet, mostly of fat and complex carbohydrates, will mimic fasting and increase resiliency to protect patients from the adverse effects of cancer treatments, by managing the adverse side effects of immune checkpoint inhibitors (ICI) treatments in select cancer patients. The fast mimicking diet (FMD) (Xentigen®) is a calorie restrictive, low-calorie, low-protein, high complex carbohydrate, high-fat diet. The FMD program is a plant-based diet program designed to attain fasting-like effects while providing both macro- and micronutrients to minimize the burden of fasting and adverse effects. The FMD consists of 100% ingredients which are generally regarded as safe (GRAS) and comprises mainly of vegetable-based soups and broths, energy bars, energy drinks, cracker snacks, herbal teas, and supplements. Following a FMD may reduce the adverse effects that some cancer patients experience while following immunotherapy treatments.",[26],"2026-05-20",{"date":369,"type":45},"2026-05-22",{"date":371,"type":45},"2024-03-06",{"date":373,"type":20},"2027-03-15",{"name":375,"class":218},"Mayo Clinic",{"id":377,"slug":378,"hasResults":12,"nctId":379,"briefTitle":380,"officialTitle":381,"acronym":4,"eligibilityCriteria":382,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":383,"targetDuration":4,"studyType":21,"phases":385,"briefSummary":386,"conditions":387,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":390,"lastUpdatePostDateStruct":391,"startDateStruct":393,"completionDateStruct":395,"leadSponsor":397,"locationsCount":219},"100533263","phase-1-studying-tak-243-in-patients-with-advanced-cancer-100533263","NCT06223542","Studying TAK-243 in Patients With Advanced Cancer","A Phase I Study to Investigate the Safety of the Ubiquitin Activating Enzyme Inhibitor TAK-243 in Adult Solid Tumor and Lymphoma Patients","Inclusion Criteria:\n\n* Patients with histologically documented advanced or metastatic solid tumors with relapsed or refractory disease who have received standard-of-care or approved therapies known to confer clinical benefit, or patients with aggressive lymphomas who have received ≥ 2 prior lines of lymphoma-directed therapy and who do not have remaining effective treatment options (including transplant). Additionally, patients with indolent lymphomas must meet criteria for treatment.\n* Patients must have measurable or evaluable disease\n* Age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2\n* Hemoglobin \\>= 9 g\u002FdL (patients may be transfused to achieve this value; elevated indirect bilirubin due to post-transfusion hemolysis is allowed)\n* Absolute neutrophil count \\>= 1,000\u002FmcL\n* Platelets \\>= 75,000\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 OR =\\\u003C 5 x institutional upper limit of normal for patients with liver metastases at baseline\n* Creatinine =\\\u003C 1.5 x institutional ULN OR creatinine clearance \\>= 60 mL\u002Fmin\u002F1.73 m\\^2 by Cockcroft-Gault\n* Any prior therapy must have been completed \\>= 4 weeks, or \\>= 5 half-lives of the prior agent (whichever is shorter) prior to enrollment on protocol. Prior definitive radiation should have been completed \\>= 4 weeks prior to enrollment; prior palliative radiation should have been completed \\>= 2 weeks prior to enrollment. Patients must be \\>= 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) and should have recovered to grade 1 or baseline from any toxicities\n* Female patients who:\n\n  * Are postmenopausal (age-related amenorrhea \\>= 12 consecutive months or follicle-stimulating hormone \\> 40 mIU\u002FmL), for at least 1 year before the screening visit, OR\n  * Are surgically sterile (i.e., who had undergone hysterectomy or bilateral oophorectomy), OR\n\nIf they are of childbearing potential:\n\n* Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or\n* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, postovulation methods\\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)\n\n  * Male patients, even if surgically sterilized (i.e., status postvasectomy), who:\n* Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or\n* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \\[eg, calendar, ovulation, symptothermal, postovulation methods for the female partner\\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)\n\n  * The effects of TAK-243 on the developing human fetus are unknown. For this reason and because ubiquitin-activating enzyme inhibitors 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. 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 TAK-243 administration\n  * Ability to understand and the willingness to sign a written informed consent document\n  * Willingness to provide blood for research purposes\n  * For expansion phase patients, willingness to undergo 2 core needle biopsy procedures for research purposes if there is a lesion or lesions amenable to repeat biopsy\n  * Patients on anticoagulation therapy are eligible for this study in the absence of anticipated drug-drug interactions (DDI) between the anticoagulation agent and TAK-243. If DDI are anticipated and another anticoagulation agent that is compatible with TAK-243 exists, the patient will be transitioned to this alternative, TAK-243-compatible anticoagulation agent\n\nExclusion Criteria:\n\n* Patients who are receiving any other investigational agents\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Life-threatening illness unrelated to cancer\n* Patients with uncontrolled coagulopathy or bleeding disorder\n* Known hepatic cirrhosis or severe pre-existing hepatic impairment\n* Known cardiopulmonary disease defined as:\n\n  * Unstable angina pectoris;\n  * Congestive heart failure (New York Heart Association \\[NYHA\\] class III or IV);\n  * Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as a \\[acute coronary syndrome (ACS)\\], MI, and\u002For revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll);\n  * Cardiomyopathy\n* Clinically significant arrhythmia:\n\n  * History of polymorphic ventricular fibrillation or torsade de pointes,\n  * Permanent atrial fibrillation (a fib), defined as continuous a fib for \\>= 6 months,\n  * Persistent a fib, defined as sustained a fib lasting \\> 7 days and\u002For requiring cardioversion in the 4 weeks before screening,\n  * Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker) or ablation, and\n  * Patients with paroxysmal a fib or \\\u003C grade 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen\n* Prolonged rate corrected QT (QTc) interval \\>= 470 m\u002Fsec, calculated according to institutional guidelines\n* Uncontrolled high blood pressure (i.e., systolic blood pressure \\> 180 mm Hg, diastolic blood pressure \\> 95 mm Hg)\n* Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis\n* Major surgery within 14 days before the first dose of any study drug\n* Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s)\n* Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s)\n* Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for \\>= 1 month after treatment of the brain metastases. Patients on anti-seizure medications may be enrolled at the discretion of the principal investigator\n* TAK-243 is primarily metabolized by CYP3A4\u002F5. Therefore, the concomitant use of strong inhibitors of CYP3A4\u002F5 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir) and strong inducers of CYP3A4\u002F5 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) is not permitted from 14 days prior to enrollment until the end of the study\n\n  * TAK-243 is a substrate for both organic anion transporting polypeptides (OATP) in human hepatocytes and the drug efflux transporter BCRP (ABCG2). Therefore, concomitant use of drugs that are strong inhibitors of BCRP or OATP is not permitted from 14 days prior to enrollment until the end of the study\n  * Other medications that are prohibited while on TAK-243 treatment include herbal medications\u002Fpreparations (except for vitamins). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of\n  * 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 undergoing vaccination with live vaccines and live attenuated vaccines in the 30 days prior to receiving TAK-243, during the study, and for 100 days after the last dose of study drug. Inactivated vaccines are permitted\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAK-243\n* Patients with evidence of chronic hepatitis B virus (HBV) infection who are currently on treatment are eligible if they have an undetectable HBV viral load\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* Known human immunodeficiency virus (HIV)-positive patients who meet the following criteria will be considered eligible:\n\n  * CD4 count \\> 350 cells\u002Fmm\\^3\n  * Undetectable viral load for 6 months prior to enrollment\n  * Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents\n  * No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections\n* Pregnant and lactating\u002Fbreast-feeding women are excluded from this study because TAK-243 is a UAE-inhibiting agent with the potential for teratogenic or abortifacient effects and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TAK-243",{"count":384,"type":20},95,[65],"This phase I trial studies the side effects and best dose of ubiquitin-activating enzyme (UAE) inhibitor TAK-243 (TAK-243) in treating patients with a solid tumor 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) and in patients with lymphoma. TAK-243 is a drug that binds to and inhibits the ubiquitin-activating enzyme, an enzyme that is more active on cancer cells than healthy cells, inhibiting tumor cell proliferation and survival.",[388,26,389,32,36,268],"Advanced Lymphoma","Indolent Non-Hodgkin Lymphoma","2026-05-12",{"date":392,"type":45},"2026-05-13",{"date":394,"type":45},"2025-03-24",{"date":396,"type":20},"2027-04-15",{"name":51,"class":52},{"id":399,"slug":400,"hasResults":12,"nctId":401,"briefTitle":402,"officialTitle":403,"acronym":4,"eligibilityCriteria":404,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":405,"targetDuration":4,"studyType":21,"phases":407,"briefSummary":408,"conditions":409,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":390,"lastUpdatePostDateStruct":410,"startDateStruct":411,"completionDateStruct":413,"leadSponsor":415,"locationsCount":219},"100492390","phase-1-testing-how-the-body-responds-to-the-drug-cbx-12-in-patients-with-advanced-solid-cancers-100492390","NCT05691517","Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers","Pilot Study of CBX-12 Pharmacodynamics in Patients With Advanced Solid Tumors","Inclusion Criteria:\n\n* Patients must have histologically confirmed solid tumors with metastatic disease that have progressed after \\>= 1 line of prior therapy\n* Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, with 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\n* Age \\>= 18 years of age\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2 (Karnofsky \\>= 60%)\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Hemoglobin \\>= 9 g\u002FL\n* Platelets \\>= 100,000\u002FmcL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN)\n\n  * However, patients with known Gilbert disease who have serum bilirubin level of up to 3 mg\u002Fdl may be enrolled\n* International normalized ratio (INR) or activated partial thromboplastin time (aPTT) =\\\u003C 1.5 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\n\n  * AST and\u002For ALT =\\\u003C 5 x ULN for patients with liver involvement\n* Potassium ≥ lower limit of normal (LLN)\n\n  * Subjects may receive supplementation to meet this eligibility criteria\n* Magnesium ≥ LLN\n\n  * Subjects may receive supplementation to meet this eligibility criteria\n* Ionized\u002Fcorrected calcium ≥ LLN\n\n  * Subjects may receive supplementation to meet this eligibility criteria\n* Creatinine =\\\u003C 1.5 x institutional ULN or creatinine clearance levels \\>= 60 ml\u002Fmin based on the Cockcroft-Gault formula\n* Oxygen (O2) saturation \\> 90% on room air\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For these patients, an HIV viral load test must be completed within 28 days prior to enrollment\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 \\>= 1 month after treatment of the brain metastases\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 CBX-12 on the developing human fetus are unknown. For this reason and because biologicals conjugated to topoisomerase 1 inhibitor 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 or abstinence) prior to study entry and for the duration of study participation and for at least 4 months 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 CBX-12 and for 4 months after cessation of treatment. 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 CBX-12 administration\n* Willingness to provide biopsy samples for research purposes\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* Patients must have recovered from clinically-significant adverse-events of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia)\n* Eligibility of subjects receiving any medications or substances with the potential to affect the activity of CBX-12 or exatecan will be determined following review of their cases by the Principal Investigator\n* Patients who are receiving any other investigational agents\n* Patients taking medication known to prolong the QT interval, or receiving any medications or substances that are strong CYP3A4 or CYP1A2 inhibitors or inducers, and sensitive substrates of CYP3A or CYP2B6 with a narrow therapeutic index are ineligible, if they cannot be transferred to alternative medication. Patients on substrates of OATP1B1 and OATP1B3 should be excluded unless they can be transferred on alternative medication. 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* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CBX-12 (e.g., other topoisomerase I inhibitors) or the inactive ingredients in the drug product\n* Patients with uncontrolled intercurrent illness that would limit compliance with study requirements\n* Pregnant women are excluded from this study because CBX-12 is an investigational agent with unknown potential for teratogenic or abortifacient effects. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) for the duration of study participation and for at least 4 months after the last dose of the study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother and because it is not known if the agent can be excreted in human milk, breastfeeding should be discontinued while the mother is taking CBX-12 and for 4 months after cessation of treatment",{"count":406,"type":20},35,[65],"This phase I trial studies how well CBX-12 works in treating patients with solid tumors that have spread from where they first started (primary site) to started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or other places in the body (metastatic). CBX-12 works by binding to a protein called TOP1 that is present inside the cells. This allows CBX-12 to kill the cancer cells by damaging their DNA, resulting in cancer cell death. This trial is being done to find out if this approach is better or worse than the usual approach for advanced cancers.",[26,32],{"date":392,"type":45},{"date":412,"type":45},"2024-06-12",{"date":414,"type":20},"2026-10-15",{"name":51,"class":52},{"id":417,"slug":418,"hasResults":12,"nctId":419,"briefTitle":420,"officialTitle":421,"acronym":4,"eligibilityCriteria":422,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":423,"targetDuration":4,"studyType":21,"phases":425,"briefSummary":426,"conditions":427,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":454,"lastUpdatePostDateStruct":455,"startDateStruct":457,"completionDateStruct":459,"leadSponsor":461,"locationsCount":219},"100401729","phase-1-trifluridinetipiracil-and-talazoparib-for-the-treatment-of-patients-with-locally-advanced-or-metastatic-colorectal-or-gastroesophageal-cancer-100401729","NCT04511039","Trifluridine\u002FTipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer","A Phase I Study of Trifluridine\u002F Tipiracil Plus the Poly (ADP) Ribose Polymerase Inhibitor Talazoparib in Advanced Cancers","Inclusion Criteria:\n\n* Histologically or cytologically confirmed CRC or EGC adenocarcinoma that is locally advanced or metastatic (Cohort A); histologically or cytologically confirmed p53mt\u002FRASonc (Cohort B1) or p53mt\u002FRASwt CRC (Cohort B2) that is locally advanced or metastatic. Patients with adenocarcinoma histology only are allowed to participate.\n* Has received at least one prior line of therapy with progression or intolerance\n* Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present\n* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n* Life expectancy \\>= 3 months by investigator assessment\n* Hemoglobin \\>= 9 g\u002FdL\n* Absolute neutrophil count \\>= 1500\u002Fmm\\^3\n* Platelet count \\>= 100,000\u002Fmm\\^3 without transfusion or growth factor support\n* Creatinine \\\u003C 1.5 upper limit of normal (ULN) or creatinine clearance \\> 60 mL\u002Fmin\n* Total bilirubin \\\u003C 1.5 x ULN\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 2.5 x ULN or \\\u003C x 5 ULN in the presence of liver metastasis\n* Albumin \\> 3 g\u002FdL\n* Ability to swallow oral medications\n* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) 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\n* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee\u002FInstitutional Review Board approved written informed consent form prior to receiving any study related procedure\n\nExclusion Criteria:\n\n* Systemic antineoplastic therapy within 2 weeks prior to day -14 (Dose Escalation, Cohort A) or Cycle 1 day 1 (Dose Expansion, Cohorts B1 and B2) or within the past 6 weeks if this treatment is mitomycin C or nitrosourea\n* Radiotherapy within the past 2 weeks excluding palliative radiotherapy to painful bone lesions\n* Prior treatment with PARP inhibitor, FUDR or FTD\u002FTPI\n* Any condition that in the investigator's opinion can limit absorption of FTD\u002FTPI or talazoparib from the gastrointestinal (GI) tract\n* Gastrointestinal obstruction (without diversion) or perforation within 4 weeks from initiation of day -14 (Dose Escalation, Cohort A) or Cycle 1 Day 1 (Dose Expansion, Cohorts B1 and B2.\n* Refractory ascites (requiring weekly or more frequent paracentesis or permanent indwelling peritoneal catheter)\n* Untreated central nervous system (CNS) disease. Patients with leptomeningeal disease are ineligible but patients with treated, stable CNS metastasis for at least 4 weeks are allowed to participate\n* Significant cardiac disease defined as congestive heart failure stage III or IV (New York Heart Association \\[NYHA\\]), acute coronary event, cerebrovascular event, peripheral arterial embolic event, venous thromboembolic event (pulmonary embolism or lower extremity deep vein thrombosis), or ventricular arrhythmia within the past 3 months\n* Other malignancy requiring active therapy\n* Presence of toxicities from prior therapy of grade 2 or higher\n* Active infection requiring antibiotic therapy\n* Known human immunodeficiency virus (HIV) or hepatitis B infection or untreated hepatitis C infection. Patients with treated hepatitis C infection and undetectable viral load are allowed to participate\n* Any history of myelodysplastic syndrome, acute leukemia, or bone marrow transplant\n* Pregnant or nursing female participants\n* Unwilling or unable to follow protocol requirements\n* Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug",{"count":424,"type":20},45,[65],"This phase I trial investigates the side effects and best dose of talazoparib when given together with trifluridine\u002Ftipiracil for the treatment of patients with colorectal or gastroesophageal cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Drugs used in the chemotherapy, such as trifluridine\u002Ftipiracil, 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. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving talazoparib with trifluridine\u002F tipiracil may inhibit certain enzymes in the cells that are responsible for tumor cell growth.",[26,428,429,430,431,432,433,434,435,436,437,438,439,440,441,442,443,444,445,446,447,167,448,449,450,168,451,452,453],"Clinical Stage III Gastroesophageal Junction Adenocarcinoma","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma A","Locally Advanced Colorectal Carcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Metastatic Colorectal Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Pathologic Stage III Gastroesophageal Junction Adenocarcinoma","Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma","Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma","Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma","Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma","Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma","Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IIIB 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","Stage IIIA Colorectal Cancer AJCC v8","Stage IIIB Colorectal 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","2026-04-30",{"date":456,"type":45},"2026-05-04",{"date":458,"type":45},"2021-06-08",{"date":460,"type":20},"2029-04-01",{"name":462,"class":218},"Roswell Park Cancer Institute",{"id":464,"slug":465,"hasResults":12,"nctId":466,"briefTitle":467,"officialTitle":468,"acronym":4,"eligibilityCriteria":469,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":470,"targetDuration":4,"studyType":21,"phases":472,"briefSummary":473,"conditions":474,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":511,"lastUpdatePostDateStruct":512,"startDateStruct":514,"completionDateStruct":516,"leadSponsor":518,"locationsCount":278},"100513775","phase-2-at-home-cancer-directed-therapy-versus-in-clinic-for-the-treatment-of-patients-with-advanced-cancer-100513775","NCT05969860","At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer","Cancer CARE Beyond Walls - A Pilot of a Randomized, Pragmatic Trial of Cancer Directed Therapy Administration in the Patients' Homes Versus in Clinic","Inclusion Criteria:\n\n* Female or male patients with histologically confirmed malignancy. Patients with hepatocellular carcinoma (HCC) are eligible based on imaging diagnosis along; histologic confirmation is not required.\n* Participant must be receiving a standard-of-care treatment regimen listed in this protocol that is being used in accordance with standard medical practice. Specifically, it must be either a) FDA-approved for the participant's disease indication, or b) recommended in nationally recognized professional guidelines (e.g. NCCN, ASCO, ASH, etc.) as standard of care for the disease indication. Off-label use is permitted only if supported by such guidelines.\n\n  * Note, patients diagnosed with any of the following disease types may receive any of the eligible regimens listed. Additionally, patients receiving immunotherapy, such as nivolumab or pembrolizumab, may receive these infusions in home supplemental to any of the regimens identified. Patients may receive any combination of any above listed medications or regimens:\n  * Eligible disease cancer types:\n\n    * Anal cancer\n    * Appendiceal carcinoma\n    * Basal cell carcinoma\n    * Bladder cancer\n    * Biliary cancer\n    * Breast cancer\n    * Central Nervous System malignancy including glioblastoma\n    * Cervical cancer\n    * Cholangiocarcinoma\n    * Colorectal carcinoma\n    * Endometrial cancer\n    * Fallopian tube cancer\n    * Gastroesophageal cancer \\[including gastric, esophageal, and gastroesophageal junction (GEJ) cancers\\]\n    * Germ cell carcinoma\n    * Head and Neck cancer\n    * Hepatocellular Carcinoma\n    * Liver\n    * Lung\n    * Lymphoma\n    * Melanoma\n    * Merkel Cell\n    * Multiple Myeloma\n    * Myelodysplastic syndrome\n    * Myeloid Disorders\n    * Neuroendocrine carcinoma\n    * Ovarian cancer\n    * Pancreatic adenocarcinoma\n    * Penile carcinoma\n    * Peritoneal carcinoma\n    * Prostate cancer\n    * Renal cell cancer\n    * Sarcoma\n    * Squamous cell Carcinoma of the Skin\n    * Testicular cancer\n    * Urethral carcinoma\n    * Vaginal carcinoma\n    * Vulvar carcinoma\n  * Eligible Regimens\n\n    * Fluorouracil (5-FU) +\u002F- leucovorin +\u002F- bevacizumab +\u002F- trastuzumab\n    * 5FU +\u002F- leucovorin +\u002F- bevacizumab +\u002F- nivolumab\n    * Atezolizumab +\u002F- bevacizumab\n    * Atezolizumab +\u002F- bevacizumab + cobimetinib, atezolizumab +\u002F- bevacizumab + vemurafenib, atezolizumab +\u002F- bevacizumab + cobimetinib + vemurafenib\n    * Avelumab\n    * Avelumab + axitinib\n    * Bevacizumab\n    * Bevacizumab + capecitabine\n    * Bevacizumab + irinotecan (+\u002F- capecitabine)\n    * Bevacizumab + olaparib, bevacizumab + lenvatinib, bevacizumab + niraparib, bevacizumab + rucaparib\n    * Bevacizumab + Temozolomide, Bevacizumab + Lomustine, or Bevacizumab + everolimus\n    * Bevacizumab + trifluridine\u002Ftipiracil\n    * Bortezomib\n    * Bortezomib + cyclophosphamide, bortezomib + lenalidomide, bortezomib + pomalidomide, bortezomib + selinexor\n    * Bortezomib + venetoclax\n    * Carfilzomib\n    * Carfilzomib + cyclophosphamide, carfilzomib + lenalidomide, carfilzomib + pomalidomide, carfilzomib + selinexor\n    * Carfilzomib + venetoclax\n    * Cemiplimab\n    * Cisplatin\n    * Cisplatin\u002F5-FU\n    * Cisplatin\u002Fetoposide\n    * Cisplatin + durvalumab\n    * Cisplatin + gemcitabine\n    * Cisplatin + gemcitabine + durvalumab\n    * Daratumumab (+ oral \\[PO\\] cyclophosphamide, lenalidomide, pomalidomide, or selinexor)\n    * Daratumumab + bortezomib (+ PO cyclophosphamide, lenalidomide, pomalidomide, or selinexor)\n    * Daratumumab + carfilzomib (+ PO cyclophosphamide, lenalidomide, pomalidomide, or selinexor)\n    * Degarelix\n    * Durvalumab\n    * Durvalumab + tremelimumab\n    * Eribulin\n    * FOLFIRI +\u002F- bevacizumab (5FU +\u002F- leucovorin + irinotecan)\n    * Fam-trastuzumab deruxtecan\n    * Fulvestrant\n    * Fulvestrant + ribociclib, fulvestrant + abemaciclib, fulvestrant + palbociclib, fulvestrant + alpelisib, or fulvestrant + capivasertib\n    * Gemcitabine\n    * Gemcitabine + durvalumab\n    * Gemcitabine + paclitaxel protein-bound\n    * Goserelin acetate\n    * Irinotecan\n    * Irinotecan + capecitabine\n    * Lanreotide\n    * Leuprolide\n    * Nivolumab\n    * Nivolumab + cabozantinib\n    * Nivolumab-relatlimab\n    * Octreotide\n    * Paclitaxel\n    * Pembrolizumab\n    * Pembrolizumab + axitinib, pembrolizumab + lenvatinib, pembrolizumab + capecitabine, pembrolizumab + dabrafenib +\u002F- trametinib, pembrolizumab + trametinib)\n    * Pemetrexed\n    * Pertuzumab\n    * Pemetrexed + pembrolizumab\n    * Rituximab\n    * Trastuzumab + paclitaxel\n    * Trastuzumab with or without pertuzumab maintenance (SQ or IV) (+\u002F- tucatinib +\u002F- capecitabine)\n    * Decitabine\n    * These regimens can be used only if patients are receiving one of the regimens above:\n\n      * Darbepoetin-alfa\n      * Epoetin\n      * Filgrastim\n* Note: Female or male patients with histologically confirmed malignancy who are currently receiving treatment with one of the above eligible regimens may receive supportive care medications for treatment or prevention of bone metastases, including agents such as:\n\n  * Zoledronic acid\n  * Denosumab\n* Patient has had adequate tolerability of their clinical standard of care cancer treatment in the opinion of their treating physician and no drug-related infusion reactions prior to consent\n* Patients who according to documentation from their treating provider plan to continue the treatment regimen they are currently prescribed for at least 24 weeks from the start of cycle following randomization.\n* Residing within the area serviced by supplier and paramedic network\n* Residence has wireless fidelity (wifi) to enable a reliable connection with the remote Command Center or it is suitable for connection through a wireless network solution\n* Age \\>= 18 years at time of registration\n* Signed informed consent form by patient\n* Willing and able to comply with the study protocol in the investigator's judgement\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2\n* Ability to complete questionnaire(s) by themselves or with assistance\n* RANDOMIZATION ELIGIBILITY CRITERIA: In addition to the criteria above, confirmation by the CCBW Command Center that the patient has adequate tolerability to the standard of care cancer therapy and no drug-related infusion reactions since pre-registration and prior to registration\n\nExclusion Criteria:\n\n* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm. Note: Patients are permitted concomitant standard of care oral drugs such as ribociclib, abemaciclib, or palbociclib in combination with endocrine therapy (e.g., Leuprolide, fulvestrant intramuscular \\[IM\\], etc.); tucatinib and capecitabine in combination with trastuzumab and pertuzumab for HER2 positive breast cancer; dexamethasone, cyclophosphamide, lenalidomide or pomalidomide for multiple myeloma; temozolomide, lomustine, or afinitor in combination with avastin for glioblastoma. In addition, all oral anti-hormonal agents for breast and prostate cancer are permitted (e.g., tamoxifen, arimidex, abiraterone, etc.) if used in combination with any of the drugs\n* Requiring 24\u002F7 assistance with activities of daily living (ADLs)\n* Current inpatient hospitalization (excluding admission to the Advanced Care at Home program)\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Cardiac arrhythmia\n  * Myocardial infarction =\\\u003C 6 months\n  * Wound healing disorder\n  * Or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements",{"count":471,"type":20},220,[23],"This clinical trial studies the effect of cancer directed therapy given at-home versus in the clinic for patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Currently most drug-related cancer care is conducted in infusion centers or specialty hospitals, where patients spend many hours a day isolated from family, friends, and familiar surroundings. This separation adds to the physical, emotional, social, and financial burden for patients and their families. The logistics and costs of navigating cancer treatments have become a principal contributor to patients' reduced quality of life. It is therefore important to reduce the burden of cancer in the lives of patients and their caregivers, and a vital aspect of this involves moving beyond traditional hospital and clinic-based care and evaluate innovative care delivery models with virtual capabilities. Providing cancer treatment at-home, versus in the clinic, may help reduce psychological and financial distress and increase treatment compliance, especially for marginalized patients and communities.",[475,190,476,477,478,479,480,481,482,483,484,485,486,487,26,488,489,490,491,492,493,494,495,496,266,291,497,498,192,499,388,500,194,501,502,503,195,504,505,506,507,508,509,510],"Advanced Anal Carcinoma","Advanced Bladder Carcinoma","Advanced Breast Carcinoma","Advanced Carcinoid Tumor","Advanced Cervical Carcinoma","Advanced Colorectal Carcinoma","Advanced Gastric Carcinoma","Advanced Glioblastoma","Advanced Head and Neck Carcinoma","Advanced HER2 Positive Breast Carcinoma","Advanced Lung Carcinoma","Advanced Lung Small Cell Carcinoma","Advanced Malignant Germ Cell Tumor","Advanced Neuroendocrine Carcinoma","Advanced Ovarian Carcinoma","Advanced Pancreatic Carcinoma","Advanced Prostate Small Cell Neuroendocrine Carcinoma","Advanced Prostate Carcinoma","Hematopoietic and Lymphoid System Neoplasm","Multiple Myeloma","Myelodysplastic Syndrome","Advanced Basal Cell Carcinoma","Advanced Esophageal Carcinoma","Advanced Fallopian Tube Carcinoma","Advanced Liver Carcinoma","Advanced Malignant Testicular Neoplasm","Advanced Merkel Cell Carcinoma","Advanced Penile Carcinoma","Advanced Primary Malignant Central Nervous System Neoplasm","Advanced Sarcoma","Advanced Skin Squamous Cell Carcinoma","Advanced Urethral Carcinoma","Advanced Vaginal Carcinoma","Advanced Vulvar Carcinoma","Advanced Appendix Carcinoma","Advanced Gastroesophageal Junction Adenocarcinoma","2026-04-15",{"date":513,"type":45},"2026-04-20",{"date":515,"type":45},"2023-08-23",{"date":517,"type":20},"2027-01-01",{"name":375,"class":218},{"id":520,"slug":521,"hasResults":12,"nctId":522,"briefTitle":523,"officialTitle":524,"acronym":4,"eligibilityCriteria":525,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":526,"targetDuration":4,"studyType":21,"phases":528,"briefSummary":529,"conditions":530,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":538,"lastUpdatePostDateStruct":539,"startDateStruct":541,"completionDateStruct":543,"leadSponsor":544,"locationsCount":93},"100443405","phase-1-testing-a-new-anti-cancer-drug-combination-entinostat-and-zen003694-for-advanced-and-refractory-solid-tumors-100443405","NCT05053971","Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors","Phase Ib\u002FII Study of ZEN003694 and Entinostat in Advanced and Refractory Solid Tumors","Inclusion Criteria:\n\n* Patients must have a) advanced or refractory solid tumor and must meet standard requirements for treatment\n* For patients in Phase 2: Patients must have locally advanced, unresectable OR metastatic pancreatic cancer refractory to standard therapy\n* For patients with solid tumors, they must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria\n* For patients with solid tumors, they must have received at least one standard of care regimen for metastatic disease\n* Age \\>= 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694, alone or in combination with entinostat, 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 \\>= 9.0 g\u002FdL (measured within 14 days prior to administration of study treatment)\n* Absolute neutrophil count (ANC) \\>= 1,500\u002FmcL (measured within 14 days prior to administration of study treatment)\n* Platelets \\>= 100,000\u002FmcL (measured within 14 days prior to administration of study treatment)\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (ULN) (measured within 14 days prior to administration of study treatment)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional ULN (measured within 14 days prior to administration of study treatment)\n* Glomerular filtration rate (GFR) \\>= 60 mL\u002Fmin\u002F1.73 m\\^2 for patients with creatinine levels above institutional normal (measured within 14 days prior to administration of study treatment)\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) and partial thromboplastin time (PTT) test \\\u003C 1.5 x ULN (measured within 14 days prior to administration of study treatment)\n* Albumin \\> 2.5 g\u002FdL (measured within 14 days prior to administration of study treatment)\n* Patients with treated brain metastases are eligible if follow-up brain imaging at least 4 weeks 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* Patients must be able to swallow and retain orally administered medication\n* Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment\n* The effects of entinostat and ZEN003694 on the developing human fetus are unknown. For this reason and because histone deacetylase inhibitor (HDACi) and BET inhibitor (BETi) agents are known to be teratogenic, women of child-bearing potential and their male partner must agree to use contraception from the time of the screening pregnancy test, continuing for the duration of study participation, and for 3 months after completing the study 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 will also be eligible\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\nExclusion Criteria:\n\n* Patients who have had any anti-cancer therapy within 30 days (or 5 half-lives, whichever is shorter) prior to the first dose of the investigational products\n* Patients who have received radiation therapy within 21 days prior to the first dose of the investigational products\n* Patients who have a diagnosis of NK cell lymphoma\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, or stable chronic grade 2 toxicities that do not overlap with presumed toxicities of entinostat or ZEN003694\n* Patients who are receiving any other investigational agents\n* Patients with known untreated or symptomatic brain or leptomeningeal metastases are excluded. Patients with previously treated CNS metastasis may be included provided that they have stable CNS disease for at least 4 weeks (confirmed by imaging) without symptoms and are off corticosteroids (above physiologic dose) for that indication\n* Patients with significant malabsorption or nausea and vomiting that would interfere with oral therapies\n* Patients with bleeding diathesis or clinically significant bleeding within the prior 6 months\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat (e.g. medications that have a benzamide structure (tiapride, remoxipride, clebopride) or ZEN003694\n* Patients receiving any medications or substances that are strong inhibitors or strong inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 and substrates of CYP1A2 must be discontinued at least 7 days prior to the first dose of ZEN003694. 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* Pregnant women are excluded from this study because entinostat is an HDACi and ZEN003694 is a BETi 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 entinostat or ZEN003694, breastfeeding should be discontinued throughout the treatment period and for at least 28 days following the last dose of study treatment if the mother is treated with entinostat or ZEN003694\n* Patients with any of the following cardiac criteria:\n\n  * Patients with a corrected QT interval calculated by the Fridericia formula (QTcF) \\> 450 msec by electrocardiogram (ECG).\n  * Concomitant use of any agent known to cause corrected QT interval (QTc) prolongation.\n  * Clinically significant conduction abnormalities or arrhythmias.\n  * Presence of a cardiac pacemaker or defibrillator with a paced ventricular rhythm limiting ECG analysis.\n  * History or evidence of current \\>= Class II congestive heart failure as defined by New York Heart Association (NYHA).\n  * History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 6 months. Subjects with a history of stent placement requiring ongoing antithrombotic therapy (e.g. clopidogrel, prasugrel) will not be permitted to enroll. Clinically significant cardiomegaly, ventricular hypertrophy, or cardiomyopathy\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* 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* Patients who have previously received ZEN003694 or who have been treated with an HDAC inhibitor or investigational BET inhibitor\n* Major surgery other than diagnostic surgery, dental surgery or stenting within 4 weeks prior to the first dose of ZEN003694",{"count":527,"type":20},49,[65,23],"This phase I\u002FII trial tests the safety, side effects, and best dose of entinostat and ZEN003694 in treating patients with solid tumors that have spread to other places in the body (advanced) or does not respond to treatment (refractory). Entinostat is in a class of drugs called histone deacetylase (HDAC) inhibitors. It may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. This trial aims to test the safety of combination therapy with entinostat and ZEN003694 in treating patients with advanced or refractory solid tumors.",[26,531,532,268,533,534,535,536,537],"Locally Advanced Pancreatic Carcinoma","Metastatic Pancreatic Carcinoma","Refractory Pancreatic Carcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","Unresectable Pancreatic Carcinoma","2026-04-09",{"date":540,"type":45},"2026-04-13",{"date":542,"type":45},"2022-11-16",{"date":42,"type":20},{"name":51,"class":52},{"id":546,"slug":547,"hasResults":12,"nctId":548,"briefTitle":549,"officialTitle":550,"acronym":4,"eligibilityCriteria":551,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":552,"targetDuration":4,"studyType":21,"phases":554,"briefSummary":555,"conditions":556,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":557,"lastUpdatePostDateStruct":558,"startDateStruct":560,"completionDateStruct":562,"leadSponsor":563,"locationsCount":219},"100415732","phase-1-talazoparib-and-palbociclib-axitinib-or-crizotinib-for-the-treatment-of-advanced-or-metastatic-solid-tumors-talacom-trial-100415732","NCT04693468","Talazoparib and Palbociclib, Axitinib, or Crizotinib for the Treatment of Advanced or Metastatic Solid Tumors, TalaCom Trial","Modular Phase 1B Hypothesis-Testing, Biomarker-Driven, Talazoparib Combination Trial (TalaCom)","Inclusion Criteria:\n\n1. Pathogenic or likely pathogenic germline or somatic gene defect as determined by local assessment and classification in at least one of the following:\n\n   * Defect in DNA Damage Response (DDR) genes specified below for each cohort or other related genes at the discretion of the principal investigator in consultation with the MD Anderson Cancer Center Institute for Personalized Cancer Therapy Precision Oncology Decision Support (PODS) group. See below for additional eligibility guidance for Arms A - C:\n   * Eligibility for Arm A (Talazoparib + Palbociclib):\n\n     * Solid tumors with defects in DDR genes such as: BRCA1\u002F2, PALB2, RAD51C\u002FD, or other related genes at the discretion of the principal investigator, or\n     * MYC-aberrant solid tumors (e.g. overexpression, amplification, mutation)\n   * Eligibility for Arm B (Talazoparib + Axitinib):\n\n     * Solid tumors with defects in DDR genes such as: BRCA1\u002F2, PALB2, RAD51C\u002FD, or other related genes at the discretion of the principal investigator, or\n     * Participants with BRCA1\u002F2 wild-type high-grade serous ovarian cancer, or\n     * Participants with metastatic castration-resistant prostate cancer without a specific and\u002For selected mutation\n   * Eligibility for Arm C (Talazoparib + Crizotinib):\n\n     * Solid tumors with defects in DDR genes such as: BRCA1\u002F2, PALB2,36 RAD51C\u002FD, or other related genes at the discretion of the principal investigator, or\n     * Solid tumors with defects in MET, ALK or ROS1 (e.g. MET mutations or amplifications, high MET expression, ALK translocations, ROS1 translocations) NOTE: Participants who are eligible for more than one Arm will be assigned according to physician preference.\n2. Histological or cytological diagnosis of a solid tumor that is advanced\u002Fmetastatic, intolerable to standard therapy, resistant to effective standard therapy, or for which no standard therapy is available.\n3. Availability of a fresh or recent tumor tissue sample from a diagnostic biopsy\u002Fsurgery or a metastatic tumor biopsy; the sample must have been obtained within 12 months prior to study enrollment. When only bone disease is present, an archival tumor tissue sample obtained within 5 years prior to study enrollment may be accepted for non-prostate cancer patients and a fresh bone biopsy may be accepted for prostate cancer patients only.\n\n   NOTE: A fresh biopsy should be encouraged for all participants at time of enrollment even if a previous biopsy is available. Optional on-treatment and at-progression biopsies will be encouraged for all participants. With agreement of the PI, if the archived tissue is not available and\u002F or it is unsafe to obtain a fresh biopsy at screening, the participant is eligible.\n4. Have measurable disease at study enrollment as defined by RECIST v1.1 with at least 1 measurable lesion that has not previously been irradiated; or participants may have bone metastatic disease evaluable by Prostate Cancer Working Group 2 (PCWG2) for participants with metastatic castration-resistant prostate cancer (mCRPC), or according to the tumor evaluation criteria best suited and accepted for the tumor type being evaluated).\n5. Age . 18 years old.\n6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1.\n7. Adequate bone marrow function (without hematopoietic growth factor or transfusion support within 14 days prior to study enrollment), including:\n\n   * Absolute Neutrophil Count (ANC) ≥ 1,500\u002Fmm3 or ≥ 1.5 x 109\u002FL\n   * Platelets ≥ 100,000\u002Fmm3 or ≥ 100 x 109\u002FL\n   * Hemoglobin ≥ 9 g\u002FdL (≥ 5.6 mmol\u002FL).\n8. Adequate renal function defined by an estimated creatinine clearance (CRCL) ≥ 60 mL\u002Fmin OR normal creatinine as assessed by 24h urine assessment (not both) will be required during the dose-escalation phase.\n\n   * Calculate CRCL according to the Cockcroft-Gault formula as: CRCL = \\[(140-age) × weight)\\]\u002F(72 x SCR)\\] × 0.85 (if female), where CRCL (creatinine clearance) is measured in mL\u002Fmin, age is expressed in years, weight in kilograms (kg), and SCR (serum creatinine) in mg\u002FdL 24h urine assessment:\n   * 24h urine assessment will be performed to assess whether creatinine is within normal limits\n   * In the event that 24h urine is used, then CRCL does not require to be calculated NOTE: Patients with moderate renal impairment (30 - 59 mL\u002Fmin) will be considered during the dose expansion phase. A reduced starting dose for talazoparib will be considered in these patients. If the dose for dose expansion is 1 mg once daily, the dose will be reduced to 0.75 mg once daily. If the expanded dose is 0.75 mg once daily, the dose will be reduced to 0.5 mg once daily.\n9. Adequate liver function including:\n\n   * Total serum bilirubin ≤ 1.5 x the upper limit of normal range (ULN)\n   * Aspartate and Alanine aminotransferase (AST and ALT) ≤ 5 x ULN.\n10. Female participants of childbearing potential must have negative serum pregnancy or urine pregnancy test at screening. Female participants of non-childbearing potential must meet at least one of the following criteria:\n\n    * Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state\n    * Have undergone a documented hysterectomy and\u002For bilateral oophorectomy\n    * Have medically confirmed ovarian failure All other female participants are considered to be of childbearing potential.\n11. Evidence of a personally signed and dated informed consent document, within 28 days prior to enrollment, indicating that the participant has been informed of all pertinent aspects of the study.\n12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.\n13. Able to swallow the study drug, have no known intolerance to study drugs or excipients, and comply with study requirements.\n\nExclusion Criteria:\n\n1. Prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation therapy within 2 weeks prior to study enrollment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed at least 2 days prior to study enrollment and no clinically significant toxicities are expected (e.g. mucositis, esophagitis).\n2. Major surgery within 4 weeks prior to study enrollment.\n3. Participants with known hypersensitivity to either talazoparib or the additional study drug to be received per treatment arm: palbociclib (Arm A), axitinib (Arm B), crizotinib (Arm C).\n4. Diagnosis of myelodysplastic syndrome (MDS).\n5. Known symptomatic brain metastases requiring steroids. Participants 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. Of note, participants who required a single dose of corticosteroids on days receiving radiation treatment do not require a 2-week washout.\n6. Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade \\> 1). However, alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 adverse events not constituting a safety risk, based on the investigators judgement, are acceptable.\n7. Active infection requiring systemic therapy. Minor infections, e.g. periodontal infection or urinary tract infection (UTI), which may be treated with short term oral antibiotics are allowed.\n8. Participants with known uncontrolled HIV virus or Acquired immunodeficiency syndrome. Note: Patients with history of controlled HIV virus will be considered eligible for this trial.\n9. Participants with uncontrolled Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Note: Participants with controlled hepatitis B or hepatitis C will be considered eligible for this trial.\n10. Clinically significant cardiovascular disease, including any of the following:\n\n    * Myocardial infarction or symptomatic cardiac ischemia within 6 months before screening;\n    * Congestive heart failure New York Heart Association class III or IV;\n    * History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1 year before screening;\n    * History of Mobitz II second degree or third degree heart block unless a permanent pacemaker is in place;\n    * Hypotension as indicated by systolic blood pressure \\\u003C86 mm Hg at screening;\n\n      * Bradycardia as indicated by a heart rate of \\\u003C45 beats per minute on the screening electrocardiogram;\n      * For part B participants only: Uncontrolled hypertension as indicated by systolic blood pressure \\>140 mm Hg or diastolic blood pressure \\>90 mm Hg despite optimal treatment. Participants can only be on one antihypertensive and stable doses of antihypertensives at discretion of PI.\n11. Current use of potent P-gp inhibitors within 7 days prior to enrollment: amiodarone, carvedilol, clarithromycin, cobicistat, dronedarone, erythromycin, glecaprevir\u002Fpibrentasvir, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, sofosbuvir\u002Fvelpatasvir\u002Fvoxilaprevir, telaprevir, tipranavir, valspodar, and verapamil.\n\n    • NOTE: Participants who have recently been on enzalutamide require a 28 day washout period due to longer elimination half-life of this therapy.\n12. Participants treated within the last 7 days prior to enrollment with:\n\n    • Food or drugs that are known to be strong CYP (cytochrome P-450) 3A4 inhibitors (ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit or grapefruit juice).\n\n    Drugs that are known to be strong CYP3A4 inducers (ie, carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St. John's wort.\n13. Inability to swallow capsules, known malabsorption syndrome, or other conditions that may impair absorption of study drugs.\n14. Bisphosphonate or denosumab dosage that was not stable (i.e. not the same) for at least 2 weeks before study enrollment for patients receiving these therapies.\n15. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgement of the investigator, would make the participant inappropriate for entry into this study.\n16. Medical, psychological, or social conditions that may interfere with the participant's participation in the study, or with the evaluation of the study results.\n17. Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast, bladder, or cervix, or low grade (Gleason ≤ 6) prostate cancer on surveillance without any plans for treatment intervention (e.g. surgery, radiation, or castration), or other early-stage low risk cancers.\n18. Pregnant female participants; breastfeeding female participants; fertile male participants; and female participants of childbearing potential who are unwilling or unable to use 2 methods of contraception for the duration of the study and for at least 7 months after the last dose of study drugs for female participants or 4 months after the last dose of study drugs for male participants, whichever is later for the individual patient. Male participants are prohibited from sperm donation while enrolled in this study and for 4 months after the last dose of the study drugs.\n\nHighly effective methods of contraception are those that alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly. These methods include:\n\n* Established use of oral, inserted, or injected or implanted hormonal methods of contraception are allowed provided the participant remains on the same treatment throughout the entire study and has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness.\n* Correctly placed copper containing intrauterine device (IUD).\n* Male condom or female condom used with spermicide (i.e. foam, gel, film, cream or suppository).\n* Male sterilization with appropriately confirmed absence of sperm in the post-vasectomy ejaculate.\n* Bilateral tubal ligation or bilateral oophorectomy.",{"count":553,"type":20},111,[65],"This phase Ib trial is to find out the best dose, possible benefits and\u002For side effects of talazoparib when given in combination with palbociclib, axitinib, or crizotinib in treating patients with solid tumors that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). PARPs are proteins that help repair damaged DNA, the genetic material that serves as the body's instruction book. PARP inhibitors, such as talazoparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Palbociclib, axitinib, and crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving talazoparib in combination with palbociclib, axitinib, or crizotinib may help control locally advanced or metastatic solid tumors.",[26,32,36],"2026-03-11",{"date":559,"type":45},"2026-03-13",{"date":561,"type":45},"2020-12-01",{"date":149,"type":20},{"name":332,"class":218},{"id":565,"slug":566,"hasResults":12,"nctId":567,"briefTitle":568,"officialTitle":569,"acronym":4,"eligibilityCriteria":570,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":571,"targetDuration":4,"studyType":21,"phases":573,"briefSummary":574,"conditions":575,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":579,"lastUpdatePostDateStruct":580,"startDateStruct":582,"completionDateStruct":584,"leadSponsor":586,"locationsCount":219},"100607487","phase-1-tr-002-for-the-treatment-of-advanced-unresectable-or-metastatic-solid-tumors-and-unresectable-or-metastatic-refractory-pancreatic-adenocarcinoma-100607487","NCT07189195","TR-002 for the Treatment of Advanced, Unresectable or Metastatic Solid Tumors and Unresectable or Metastatic, Refractory Pancreatic Adenocarcinoma","A Phase 1 Study of Bisaminoquinoline Derivative (TR-002) for Injection for Advanced Treatment-Refractory Solid Tumors","Inclusion Criteria:\n\n* Aged 18 or over at the time of consent\n* Pathology or histology-confirmed metastatic or unresectable solid tumor for which standard systemic treatments are no longer effective or not tolerated\n* For the expansion cohort, participants must have pathology or histology-confirmed metastatic or unresectable pancreatic adenocarcinoma that is refractory and\u002For intolerant to all standard-of-care systemic treatments (including gemcitabine, nab-paclitaxel, fluoropyrimidine, oxaliplatin, and irinotecan)\n* Participants in dose escalation may have measurable and\u002For non-measurable disease. Imaging for disease assessment of measurable and non-measurable disease must be completed within 28 days prior to registration. Participants in dose expansion must have measurable disease per Response Evaluation Criteira in Solid Tumors (RECIST) 1.1\n* Adequate cardiac function, assessed by multiple-gated acquisition (MUGA) scan or echocardiography (left ventricular ejection fraction of \\> 50%)\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2\n* Absolute neutrophil count ≥ 1,000\u002FmcL\n* Platelets ≥ 75,000\u002FmcL\n* Hemoglobin ≥ 8g\u002FdL\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (\\\u003C 3 x ULN in patients with known Gilberts)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 × institutional ULN (\\\u003C 5 x ULN in patients with known liver metastases)\n* Creatinine ≤ 1.5 x institutional ULN OR glomerular filtration rate (GFR) ≥ 60 mL\u002Fmin\u002F1.73 m\\^2\n* For people of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method through 3 months following the last dose of study treatment\n* Provision of signed and dated informed consent form\n* Stated willingness to comply with all study procedures and availability for the duration of the study\n\nExclusion Criteria:\n\n* Lactating or pregnant patients or patients of reproductive potential not willing to use effective methods of contraception\n* Clinically significant toxicities from most recent therapy or intervention prior to study enrollment that have not resolved to baseline or grade 1 (exceptions include alopecia and grade 2 sensory neuropathy)\n* Participant with a history of the following significant cardiovascular disease will be excluded:\n\n  * Participant has a history of myocardial infarction or unstable angina within 6 months prior to day 1.\n  * Participant has New York Heart Association (NYHA) Class II or greater congetive heart failure (CHF).\n  * History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to study treatment.\n  * Participant has cardiac arrhythmia, complete left bundle branch block, obligate use of a cardiac pacemaker, long QT syndrome or right bundle branch block with left anterior hemiblock (bifascicular block).\n  * History of congenital long QT syndrome or prolonged corrected QT interval (QTc) \\> 470 msec for females and males using Fridericia's formula (unless a pacemaker is in place or additional clinically non-significant condition such as bundle-branch block necessitating use of an alternate formula per cardiologist calculation) or uncorrectable abnormalities in serum electrolytes (i.e., sodium, potassium, calcium, magnesium, phosphorus). An average of triplicate readings for assessing QTc interval may be used\n* Active bacterial, fungal, and viral infection, as documented by positive culture, radiological imaging techniques, septic fever, or septic shock symptoms\n* Known hypersensitivity to 4-aminoquinolone compounds\n* Retinal or visual field changes of any etiology\n* History of psoriasis\n* History of porphyria\n* Known glucose-6-phosphate dehydrogenase (G6PD) deficiency\n* History of seizure disorder\n* Any other condition that could compromise the subject's safety or put the study outcomes at undue risk",{"count":572,"type":20},52,[65],"This phase I trial tests the safety, side effects and best dose of TR-002 for the treatment of solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable), that has spread from where it first started (primary site) to other places in the body (metastatic) and unresectable or metastatic pancreatic adenocarcinoma that does not respond to treatment (refractory). Chemotherapy drugs, such as TR-002, 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. TR-002 may be safe and tolerable in treating patients with advanced, unresectable or metastatic solid tumors and unresectable or metastatic, refractory pancreatic adenocarcinoma.",[26,32,576,577,535,536,40,578],"Metastatic Pancreatic Adenocarcinoma","Refractory Pancreatic Adenocarcinoma","Unresectable Pancreatic Adenocarcinoma","2026-03-03",{"date":581,"type":45},"2026-03-05",{"date":583,"type":45},"2025-11-07",{"date":585,"type":20},"2030-02-07",{"name":587,"class":218},"University of California, Davis",{"id":589,"slug":590,"hasResults":12,"nctId":591,"briefTitle":592,"officialTitle":593,"acronym":4,"eligibilityCriteria":594,"healthyVolunteers":340,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":595,"targetDuration":4,"studyType":21,"phases":597,"briefSummary":598,"conditions":599,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":579,"lastUpdatePostDateStruct":601,"startDateStruct":602,"completionDateStruct":604,"leadSponsor":606,"locationsCount":219},"100438074","phase-2-impact-of-project-echo-on-improving-the-quality-of-palliative-care-in-patients-with-advanced-cancer-and-their-caregivers-in-underserved-areas-of-kenya-nigeria-ghana-south-africa-india-and-ethiopia-100438074","NCT04984551","Impact of Project ECHO on Improving the Quality of Palliative Care in Patients With Advanced Cancer and Their Caregivers in Underserved Areas of Kenya, Nigeria, Ghana, South Africa, India, and Ethiopia","ECHO Telementoring to Improve Quality Palliative Care in Underserved Areas of Kenya, Nigeria, Ghana, South Africa, India, and Ethiopia","Inclusion Criteria:\n\n* PATIENT: Scheduled to receive treatment at participating primary care practice for advanced cancer\n* PATIENT: 18 years or older\n* PATIENT: Willing to be accessible to the research team for follow-up by telephone or in person\n* PATIENT: Prognosis of at least 1 year as ascertained by the treating physician\n* PATIENT: Able to read and understand English as assessed by the treating physician\n* CAREGIVER: Identified or self-identified as primary caregiver of the patient\n* CAREGIVER: Willing to be accessible to the research team for follow-up by telephone or in person\n* CAREGIVER: 18 years or older\n* CAREGIVER: Able to read and understand English as assessed by the treating physician\n* ECHO PARTICIPANT: Participant must be a health care provider interested to participate in the study for 2 years and understand the protocol and provide consent\n* ECHO PARTICIPANT: Able to read and understand English as assessed by principal investigator (PI)\n\nExclusion Criteria:\n\n* Unable to understand and sign consent",{"count":596,"type":20},312,[23],"This trial investigates the experience and satisfaction of care in patients with cancer that has spread to other places in the body (advanced) and their caregivers living in underserved areas of Kenya, Nigeria, Ghana, South Africa, India and Ethiopia as part of Project Extension for Community Healthcare Outcomes (ECHO). Project ECHO is a model of medical education and care management that empowers clinicians to provide better care to more people where they live. Understanding the experiences and satisfaction of patients and caregivers may help improve healthcare workforce capacity and increase access to specialty care for the world's rural and underserved populations.",[26,600],"Hematopoietic and Lymphoid Cell Neoplasm",{"date":581,"type":45},{"date":603,"type":45},"2020-08-24",{"date":605,"type":20},"2026-12-31",{"name":332,"class":218},{"id":608,"slug":609,"hasResults":12,"nctId":610,"briefTitle":611,"officialTitle":611,"acronym":4,"eligibilityCriteria":612,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":613,"targetDuration":4,"studyType":21,"phases":615,"briefSummary":616,"conditions":617,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":619,"lastUpdatePostDateStruct":620,"startDateStruct":622,"completionDateStruct":624,"leadSponsor":626,"locationsCount":219},"100442303","phase-1-phase-iii-randomized-study-of-nbtxr3-activated-by-abscopal-or-radscopal-radiation-in-combination-with-immunotherapy-anti-pd-1l-1-for-patients-with-advanced-solid-malignancies-100442303","NCT05039632","Phase I\u002FII Randomized Study of NBTXR3 Activated by Abscopal or RadScopal Radiation in Combination With Immunotherapy (Anti-PD-1\u002FL-1) for Patients With Advanced Solid Malignancies","Inclusion Criteria:\n\n1. Patients with metastatic disease in the lung and\u002For liver, or soft tissue from any primary malignancy considered incurable by local therapies.\n\n   a. One prior anti-PD-1\u002FL1 therapy allowed.\n2. The target lesion(s) must be measurable as per irRECIST and repeated measurements at the same anatomical location should be achievable.\n\n   a. Participant must have at least 2 measurable lesions at screening. i. Abscopal cohort: At least one lesion will receive NBTXR3 and high dose radiation (high dose target lesion). The other lesion(s) (non-treated target lesion) will be followed for response and it will not receive NBTXR3 or RT.\n\n   ii. RadScopal™ cohort: At least one lesion will receive NBTXR3 and high dose radiation (high dose target lesion). The other lesion(s) will only receive low dose radiation (low dose target lesion).\n3. Amenable to undergo the image guided (EBUS or CT or MRI) intratumoral injection of NBTXR3, in up to two (2) high dose target lesions, as determined by the investigator or treating physician at screening.\n\n   a. Intratumoral NBTXR3 injections only allowed in lung or liver lesions.\n4. Selected high and low dose target lesions must be amenable to receive radiation therapy as determined by the investigator or treating radiation oncologist.\n\n   1. Allowed high dose RT regimens are 50 Gy in 4 fractions or 60 Gy in 10 fractions\n   2. Allowed low dose RT for RadScopal™ cohort is 1.4 Gy per fraction for 4 - 5 fractions to only low dose-target lesion(s) determined by the investigator or treating physician.\n5. Patients can receive radiation therapy for symptomatic metastatic disease prior to enrollment or during the study a.\n6. Age ≥ 18 years\n7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2\n8. Laboratory Values at screening:\n\n   1. Hemoglobin ≥ 9.0 g\u002FdL\n   2. Absolute Neutrophil Count (ANC) ≥ 1,500\u002Fmm3\n   3. Platelet count ≥ 100,000\u002Fmm3\n   4. Leukocytes ≥ 1500\u002Fmm3\n   5. Creatinine ≤ 1.5 x upper limit of normal (ULN)\n   6. Calc. creatinine clearance \\> 30mL\u002Fmin\n   7. Total bilirubin ≤ 2.0 mg\u002FdL\n   8. AST \u002F ALT ≤ 2.0 x upper limit of normal (ULN) or ≤ 3 x ULN for patients with liver metastases\n9. For participants to be treated for lung metastases, adequate lung function with expiratory volume in 1 second (FEV1) ≥ 0.8L or ≥ 35% predicted and carbon monoxide diffusing capability (DLCO) ≥ 40% with or without bronchodilator within 30 days prior to NBTXR3 injection. Participants to be treated for liver metastasis a pulmonary function test is not required.\n10. Patients who meet the criterion above without oxygen (02), but need acute (started within 7 ± 3 days) supplemental oxygen due to tumor-caused obstruction\u002Fhypoxia are eligible, provided the amount of the O2 needed has been stable.\n11. Negative urine or serum pregnancy test ≤ 7 days prior to NBTXR3 injection in all women of child-bearing potential (WOCBP). WOCBP must agree to follow instructions for method(s) of contraception for the duration the entire study period and 160 days (\\~5.33 months) after the last dose of anti-PD-1\u002FL-1 treatment. Local laws and regulations may require use of alternative and\u002For additional contraception methods. WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements but should still undergo pregnancy testing.\n12. Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.\n\n4.2 Exclusion criteria:\n\n1. Prior radiation therapy received to the selected high dose target lesion(s)\n\n   a. Previous radiation to low dose target lesions allowed as per investigator or treating radiation oncologist discretion.\n2. Symptomatic central nervous system metastases and\u002For carcinomatous meningitis\n\n   a. Participants with previously treated brain metastases may participate if those lesions are radiologically stable (i.e., without evidence of progression for at least 4 weeks by repeat imaging at screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to NBTXR3 injection.\n3. At screening, past medical history of:\n\n   1. Interstitial lung disease\n   2. Unresolved organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia)\n   3. Any Grade 4 radiation toxicity\n   4. Unresolved, radiation or ICI related\n\n   i. Pneumonitis ii. Bronchopulmonary hemorrhage iii. Abdominal hemorrhage e. Unresolved GI related events i. Diverticulitis ii. Colitis iii. Intra-abdominal abscess iv. GI obstructions v. Abdominal carcinomatosis vi. Any known risk factor for bowel perforation\n4. History of severe (Grade ≥ 3) immune-related adverse events observed with previous immunotherapy (anti-PD-1\u002FL1) or known sensitivity (Grade ≥ 3) to any excipients.\n5. Has received any approved or investigational anti-neoplastic agent or immunotherapy within 2 weeks prior to NBTXR3 injection.\n\n   1. Except anti-PD-1\u002FL1, which will not require a washout window.\n   2. A reduced washout window may be considered for therapies with short half-lives (i.e., kinase inhibitors) after discussion with Nanobiotix and investigator.\n6. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).\n\n   a. Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement \\[≤ 10 mg prednisone\\] therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n7. Any live-virus vaccine used for prevention of infectious diseases administered within 4 weeks prior to NBTXR3 injection.\n\n   1. Except killed-virus Influenza vaccine\n   2. Exception of other vaccines (e.g. pneumonia) is at the discretion of the treating physician after conducting a personalized risk assessment on a case by case basis.\n8. Prior allogenic stem cell transplantation or organ allograft.\n9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment.\n10. Known active, uncontrolled (high viral load) HIV or hepatitis B or hepatitis C infection.\n11. Female patients who are pregnant or breastfeeding.\n12. Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 160 days (\\~5.33 months) for female participants, and 7 months for males participants or female partners of male participants that are of child-bearing potential, after the last dose of anti-PD-1\u002FL-1.\n\n    a. Acceptable methods of contraception are those that, alone or in combination, result in a failure rate of \\\u003C 1% per year when used consistently and correctly.\n13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.",{"count":614,"type":20},40,[65,23],"This phase I\u002FII trial studies the side effects and possible benefits of NBTXR3, radiation therapy, Anti PD-1 \u002F PD-L1 in treating patients with solid tumor that has spread to the lung (lung metastases) and\u002For liver (liver metastases). NBTXR3 may help make tumor cells more sensitive to the radiation therapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with Anti PD-1 \u002F PD-L1 monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving NBTXR3, radiation therapy, Anti PD-1 \u002F PD-L1 may help to control the disease.",[26,267,618,32],"Metastatic Malignant Neoplasm in the Lung","2026-02-04",{"date":621,"type":45},"2026-02-06",{"date":623,"type":45},"2023-05-08",{"date":625,"type":20},"2028-02-01",{"name":332,"class":218},{"id":628,"slug":629,"hasResults":12,"nctId":630,"briefTitle":631,"officialTitle":632,"acronym":4,"eligibilityCriteria":633,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":634,"targetDuration":4,"studyType":21,"phases":635,"briefSummary":636,"conditions":637,"keywords":643,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":648,"lastUpdatePostDateStruct":649,"startDateStruct":651,"completionDateStruct":653,"leadSponsor":654,"locationsCount":219},"100493464","phase-2-olanzapine-for-the-management-of-cancer-associated-appetite-loss-in-patients-with-advanced-esophagogastric-hepatopancreaticobiliary-colorectal-or-lung-cancer-100493464","NCT05705492","Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced Esophagogastric, Hepatopancreaticobiliary, Colorectal or Lung Cancer","ACTO: A Phase II, Randomized, Placebo-Controlled Study Evaluating Olanzapine in the Management of Cancer Cachexia","Inclusion Criteria:\n\n* Willingness to provide written informed consent\n* Individuals \\>= 18 years of age\n* Histologically confirmed advanced local or metastatic esophogastric, hepatopancreaticobiliary, colorectal, or lung cancer diagnosis within 12 weeks of screening\n* Patients with weight loss as defined by international consensus criteria (documented or patient-reported):\n\n  * ≥ 5% weight loss over the past 6 months\n  * ≥ 2% weight loss with body mass index (BMI) \\\u003C20 kg\u002Fm\\^2 or sarcopenia\n* Planned or ongoing first-line palliative antineoplastic therapy (cytotoxic chemotherapy, targeted therapy, immunotherapy, combinations) with or without radiation therapy and have not started the second cycle of first-line palliative antineoplastic therapy. Patients may have received adjuvant antineoplastic therapy at least 6 months prior to screening\n* Able to ambulate independently with or without assistive devices (e.g., cane, walker)\n* In the case of brain metastases, the individual must be asymptomatic or previously treated with a full cycle of therapy with recovery from any acute effects of radiation therapy or surgery before screening. Such individuals must have discontinued corticosteroid treatment and be neurologically stable for at least 4 weeks before screening\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Able and willing to discontinue the use of any drug or over-the-counter (OTC) product that may interact with the study drug (within a period sufficient for wash-out per the principal investigators \\[PI's\\] discretion) and thereafter while on the study\n* Willingness to comply with restrictions on chest\u002Fbreastfeeding\n* Individuals capable of childbearing and contributing viable sperm must be willing to comply with contraception requirements and not donate ova or sperm while on the study and for 1 month after that\n* A negative pregnancy test at baseline (BL) must be obtained for individuals capable of childbearing\n\nExclusion Criteria:\n\n* Plan for, or history of (within 30 days of enrollment), the use of an antipsychotic drug, including, but not limited to, risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone. This limitation does not include prochlorperazine and other phenothiazines as antiemetic therapy. The use of antipsychotics concurrent with protocol therapy will not be allowed\n* Current use of medications or supplements with the goal of enhancing appetite within ≥14 days, including:\n\n  * megestrol acetate\n  * cannabinoids (including, but not limited to dronabinol, medical cannabis, over the counter \\[OTC\\] cannabinoid products), and\u002For\n  * Corticosteroids (defined as ≥ 5mg of prednisone \\[or equivalent per day\\]), except for standard-of-care chemotherapy-induced nausea and vomiting prophylaxis\n* Known history of poorly controlled diabetes, defined as fasting morning blood sugars ≥300 mg\u002FdL or recent hemoglobin A1≥ 8. Individuals with diabetes will undergo hemoglobin A1c (HbA1c) blood testing if they do not have HbA1c results 12 weeks prior to enrollment\n* Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days before signing consent:\n\n  * Total bilirubin ≥5x upper limit of normal (ULN), aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SPGT\\]) ≥5X ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma, or hepatic metastases)\n  * Primary investigator (PI) discretion will determine continued eligibility after randomization occurs in the event the liver function test results are above the proposed ULN\n  * Renal disease requiring dialysis or calculated glomerular filtration rate (GFR) ≤ 30 mL\u002Fminute\u002F1.73 m\\^2 as calculated by the modification of diet in renal disease (MDRD) equation\n* Tube feeding or parenteral nutrition at the time of screening\n* Any condition that may negatively impact oral absorption of the study drug (including, but not limited to dysphagia, mucositis, gastrectomy, colitis, bowel obstruction, high output ileostomy) or any plan to undergo an intervention that will render such a condition\n* Recurrent ascites unresponsive to medical interventions and requires therapeutic paracentesis\n* Uncontrolled symptoms at randomization make the individual unsuitable for the study in the judgment of the PI. If uncontrolled symptoms can be effectively palliated for ≥1 week prior, enrollment may be considered at the discretion of the PI\n* Uncontrolled infection, including coronavirus disease 2019 (COVID-19), at time of randomization. Individuals with the uncontrolled infection will not be eligible as the symptomology of infection may obscure the outcomes of this study\n* Other medical or psychiatric condition, including recent (within 1 year) or active suicidal ideation\u002Fbehavior or laboratory abnormality, may increase the risk of study participation or, in the PI's judgment, makes the participant inappropriate for the study",{"count":122,"type":20},[23],"This phase II trial tests how well olanzapine works in managing cancer cachexia in patients experiencing esophagogastric, hepatopancreaticobiliary, colorectal, or lung cancer 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) -associated appetite loss while receiving non-curative cancer therapy. Loss of appetite (\"anorexia\") in the setting of cancer is a key feature of \"cachexia,\" a syndrome associated with loss of weight and muscle as well as weakness and fatigue. Olanzapine is a drug that targets key neurotransmitters (a type of molecule in the central nervous system that transmits messages to the rest of the body) that may stimulate appetite, restore caloric intake, minimize weight loss, and improve quality of life (QOL).",[26,190,497,638,432,639,640,641,485,642],"Metastatic Esophageal Carcinoma","Locally Advanced Esophageal Carcinoma","Locally Advanced Gastric Carcinoma","Metastatic Colorectal Carcinoma (mCRC)","Locally Advanced Hepatocellular Carcinoma",[644,645,646,647],"cancer","cachexia","weight loss","loss of appetite","2026-01-19",{"date":650,"type":45},"2026-01-21",{"date":652,"type":45},"2024-07-17",{"date":605,"type":20},{"name":217,"class":218},{"id":656,"slug":657,"hasResults":12,"nctId":658,"briefTitle":659,"officialTitle":660,"acronym":4,"eligibilityCriteria":661,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":662,"targetDuration":4,"studyType":21,"phases":663,"briefSummary":664,"conditions":665,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":666,"lastUpdatePostDateStruct":667,"startDateStruct":669,"completionDateStruct":671,"leadSponsor":673,"locationsCount":219},"100552275","phase-2-siltuximab-for-the-prevention-of-severe-immune-related-adverse-events-during-immune-checkpoint-inhibitor-rechallenge-in-patients-with-advanced-cancer-cires-trial-100552275","NCT06470971","Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer, CIRES Trial","Immune Checkpoint Inhibitor Rechallenge in Combination With Siltuximab Prophylaxis for Patients Who Had Prior Immune-Related Adverse Event (CIRES Trial)","Inclusion Criteria:\n\n* Males or females aged ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2\n* Patients with any advanced cancer types who would benefit from anti-PD1 or anti-PD-L1 therapy rechallenge at the investigator's discretion\n* Patients must have had prior severe irAE while on ICI monotherapy or in combination with other anticancer treatment. Severe irAE is defined as any grade 2 or higher irAE requiring treatment discontinuation and prednisone \\> 0.5 milligrams (mg)\u002Fkilogram (kg)\u002Fday (or equivalent) followed by a taper ≥ 4 weeks. Patients with history of grade 4 severe irAE need to carefully weigh the risks and benefits and might be eligible on a case-by-case basis after discussion with principal investigator (PI)\n* Recovery from prior irAEs to ≤ grade 1\n* Patients who are on prednisone ≤ 10 mg\u002Fday (d) or equivalent are allowed\n* Hemoglobin \\> 7 g\u002FdL and \\\u003C 17 g\u002FdL\n* Absolute neutrophil count (ANC) ≥ 1000 per mm\\^3\n* Platelet count ≥ 75 × 10\\^9\u002FL\n* Serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 × institutional ULN or ≤ 5 × ULN for patients with liver metastases\n* Measured or calculated creatinine clearance (CL) ≥ 30 mL\u002Fmin except patients with end-stage renal disease on hemodialysis\n* Cycle 1 day 1 of the study treatment should be at least 2 weeks since prior systemic therapy, radiotherapy, or surgery\n* Estimated life expectancy, in the judgment of the investigator, of at least 12 weeks\n* Subjects of childbearing potential must have a negative serum pregnancy test at screening\n* Subjects of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception (i.e., less than 1% failure rate), from the time of signing informed consent and for the duration of study participation through 3 months following the last dose of study drug\n\n  * Childbearing potential is defined by the following criteria: 1. Subject has not undergone a hysterectomy or bilateral oophorectomy; or 2. has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)\n  * Highly effective birth control methods (less than 1% failure rate per year if used consistently and correctly) include but are not limited to: 1. Oral, injected, or implanted hormonal method of contraception; 2. Place of intrauterine device (IUD) or system (IUS); 3. Tubal ligation (tubes tied) or a sterile partner (effective bilateral vasectomy)\n* Subjects must not breastfeed a child during the study and for 3 months after the last dose of study drug\n* Ability to understand and willingness to sign the written informed consent document\n\nExclusion Criteria:\n\n* Women who are pregnant or breastfeeding\n* Any ≥ grade 3 irAEs in which the risks outweigh the benefits per investigator's discretion (these may include but are not limited to myocarditis, myasthenia gravis, Guillain-Barré syndrome, encephalitis, myelitis, or other life-threatening events)\n* Has active autoimmune disease or irAE requiring systemic treatment with steroids (\\> 10 mg daily doses of prednisone or equivalent) or other immunosuppressive agents or any condition that, in the investigator's judgment, precludes treatment with anti-PD-1\u002FPD-L1 therapy\n* Cycle 1 day 1 of the study treatment must be at least 2 weeks beyond high dose systemic corticosteroids (prednisone \\> 0.5 mg\u002Fkg\u002Fday or equivalent); chronic steroid use up to 10 mg daily prednisone (or equivalent) is permitted\n* Other concurrent anticancer therapy except for palliative radiation and hormone therapy\n* Has a known history of HIV-1\u002F2 with detectable viral load and\u002For CD4 (cluster of differentiation 4) count \\\u003C 300\u002FmL within the previous 3 months\n* Has detectable hepatitis B virus (HBV) or hepatitis C virus (HCV) viral load polymerase chain reaction (PCR) if there is a known history of active hepatitis B or hepatitis C\n* High risk for bowel perforation per the investigator's judgment, such as history of severe diverticulitis or active ulcers or extensive gastrointestinal (GI) involvement by the tumor\n* Presence of a transplanted solid organ (with the exception of a corneal transplant more than 3 months prior to screening) or having received an allogeneic bone marrow transplant or an allogeneic peripheral blood stem cell transplant\n* Uncontrolled concomitant illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association \\[NYHA\\] class III or IV), unstable angina pectoris, myocardial infarction within 1 month prior to enrollment, uncontrolled cardiac arrhythmias, uncontrolled seizures, or severe noncompensated hypertension (systolic blood pressure \\> 180mmHg or diastolic blood pressure \\> 120mmHg)\n* Patients with a current severe infection\n* Known unmanageable allergies, hypersensitivity, intolerance to monoclonal antibodies, to murine, chimeric, human proteins or their excipients\n* Prior failure of interleukin-6 or interleukin-6 receptor targeted therapies. Prior IL-6 or IL-6 receptor-targeted therapies are permitted if the response was favorable\n* Received any investigational drug within 30 days",{"count":614,"type":20},[23],"This phase II trial studies how well giving siltuximab during the reintroduction (rechallenge) of immune checkpoint inhibitor (ICI) therapy works in preventing severe immune-related adverse events (irAEs) 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). Immune checkpoint inhibitors, such as anti-PD1 and anti-PD-L1 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. The use of ICI therapy may lead to severe irAEs that can affect essentially any organ system in the body. Severe irAEs may lead to the early stopping of life saving treatment. Most patients that stop ICI therapy early will eventually progress and require additional treatment. Sometimes the decision is made to rechallenge with ICI therapy. Many patients who developed severe irAEs during initial ICI therapy are at risk for developing severe irAEs again during the rechallenge. Siltuximab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 (IL-6). This may help lower the body's immune response and reduce inflammation. Giving siltuximab during ICI rechallenge may help prevent severe irAEs in patients with advanced cancer.",[26,165],"2026-01-15",{"date":668,"type":45},"2026-01-20",{"date":670,"type":45},"2024-07-09",{"date":672,"type":20},"2030-12-31",{"name":674,"class":218},"Yuanquan Yang",{"id":676,"slug":677,"hasResults":12,"nctId":678,"briefTitle":679,"officialTitle":680,"acronym":4,"eligibilityCriteria":681,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":682,"targetDuration":4,"studyType":684,"phases":4,"briefSummary":685,"conditions":686,"keywords":4,"overallStatus":247,"whyStopped":4,"lastUpdateSubmitDate":687,"lastUpdatePostDateStruct":688,"startDateStruct":690,"completionDateStruct":692,"leadSponsor":693,"locationsCount":219},"100429392","adoption-of-audio-recording-in-the-outpatient-supportive-care-center-100429392","NCT04871477","Adoption of Audio Recording in the Outpatient Supportive Care Center","The Adoption of Audio Recording in the Outpatient Supportive Care Center","Inclusion Criteria:\n\n* Patients with the diagnosis of advanced cancer as defined as locally advanced, recurrent or metastatic cancer. Both solid and liquid tumors are eligible for the study\n* Patients who are seen in the outpatient supportive care center at M.D. Anderson Cancer Center\n* Patients who have access to a recording device or cellphone with recording technology\n* Patients who can be contacted 7 to 11 days from the clinic visit that the recording took place\n* Patients who can sign informed consent\n* Patients who are able to read and write in English\n* Patients 18 years or older\n\nExclusion Criteria:\n\n* Patients who have been diagnosed with delirium or cognitive impairment. This will be defined by chart review along with review of the MD Anderson Symptom Inventory (MDAS) the day of clinic visit. An MDAS of 7 or greater will be considered to define delirium in this study\n* Patients who are unwilling to sign informed consent\n* Patients who have used audio recordings before in clinic visits\n* Patients who have severe hearing impairments without access to assisted devices or programs to aid in listening to the recorded material",{"count":683,"type":20},200,"OBSERVATIONAL","This study evaluates how patients feel about having an audio recording of their visit to help remember information given to them and share that information with family members and\u002For caregivers not present during a clinic visit. Information from this study may help evaluate the effectiveness of using technology to help improve patient care by recording consultation recommendations.",[26,600,29,32,36],"2026-01-13",{"date":689,"type":45},"2026-01-14",{"date":691,"type":20},"2026-01-30",{"date":89,"type":20},{"name":332,"class":218},{"id":695,"slug":696,"hasResults":12,"nctId":697,"briefTitle":698,"officialTitle":699,"acronym":4,"eligibilityCriteria":700,"healthyVolunteers":12,"sex":17,"minAge":61,"maxAge":4,"enrollmentInfo":701,"targetDuration":4,"studyType":21,"phases":703,"briefSummary":704,"conditions":705,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":706,"lastUpdatePostDateStruct":707,"startDateStruct":709,"completionDateStruct":711,"leadSponsor":712,"locationsCount":219},"100540712","phase-1-axatilimab-in-combination-with-retifanlimab-and-paclitaxel-for-the-treatment-of-patients-with-advanced-or-metastatic-solid-tumors-100540712","NCT06320405","Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced or Metastatic Solid Tumors","A Phase Ib\u002FII Study of Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced Solid Tumors","Inclusion Criteria:\n\n* Ability to comprehend the investigational nature of the study and provide informed consent. Written informed consent must be obtained prior to any study specific procedures or interventions\n* Age ≥ 18 years at the time of consent. All participants, irrespective of their gender, gender identity, race, and ethnicity, will be included\n* Certified, documented diagnosis of a metastatic solid tumor based on pathology review\n* Presence of at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and another lesion that is amenable to tumor biopsy\n* Relapsed from, or refractory to, standard of care (SOC) systemic therapy known to prolong survival or if, in the opinion of the primary treating oncologist, a clinical trial is the best option for the next line of treatment based on response and\u002For tolerability to available therapies\n* Investigational therapy is permitted after a wash-out period of 5 half-lives (if known), or 28 days, whichever is shorter, prior to study day -8. Prior use of an investigational agent for imaging, such as T cell imaging, is permitted\n* Prior treatment with taxanes. A wash-out of period of ≥ 3 months prior to day -8 must be met for enrollment. Prior anti PD-1\u002FPD-L1 therapy is allowed, but not required\n* Eastern Cooperative Oncology Group (ECOG) status (performance status \\[PS\\]) of 0-1\n* Life expectancy of greater than 12 weeks according to certified physician review\n* Hemoglobin (Hb) ≥ 8.5 g\u002FdL\n* Leukocytes ≥ 3,000\u002FmcL\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL\n* Platelets ≥ 100K\u002Fcc mL\n\n  * Values must be obtained without transfusion within 2 weeks\n* Serum creatinine (sCr) \\\u003C 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 50 mL\u002Fmin (calculated with the Cockcroft-Gault formula) for participants with creatinine (sCr) levels above institutional normal\n* Total bilirubin \\\u003C 1.5 x upper limit of normal (ULN)\n\n  * With the exception of documented Gilbert's syndrome or similar conditions, at the discretion of the principal investigator (PI). Clinical chemistry testing may be adjusted, as clinically indicated\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 2.5 x ULN\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 (NYHA) Functional Classification. To be eligible for this trial, patients should be class 2B or better\n* Corrected QT interval Fridericia's formula (QTcF) of \\\u003C 480 ms on a 12 lead electrocardiogram (EKG), except for participants with atrioventricular pacemakers or other conditions (e.g., right bundle branch block) that render the QT measurement invalid\n* Willingness to modify concomitant drug regimens, at the recommendation and discretion of pharmacy services, including the use of known substrates or inhibitors of CYP2C8 and CYP3A4\n* Physiologic maintenance doses of corticosteroids (≤ 10 mg\u002Fday of prednisone or equivalent) are permitted. Examples include: Asthma treatment; topical ocular, intra-articular, or intranasal steroids with minimal systemic absorption; and brief courses of corticosteroids for prophylaxis\n* Patients with CD4+ T-cell (CD4+) counts ≥ 350 cells\u002FuL are eligible regardless of HIV serology\n\n  * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment are eligible\n  * In the case of ongoing treatment with antiretroviral therapy (ART), medication adjustment may be necessary for the duration of treatment. A wash-out period may be necessary, at the recommendation of the institutional research pharmacy service (RPS)\n* Evidence of chronic hepatitis B virus (HBV) infection (i.e., hepatitis B surface antigen \\[HBsAg\\]-positive, undetectable or low HBV deoxyribonucleic acid \\[DNA\\], and normal ALT) in the absence of HBV therapy, or serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and hepatitis B virus core antibody \\[anti-HBc\\]-positive) is permitted\n* History of hepatitis C virus (HCV) infection is permitted given prior curative treatment or undetectable HCV viral load by serology or polymerase chain reaction (PCR) testing\n\n  * Patient who are HCV antibody (Ab) seropositive but HCV ribonucleic acid (RNA) negative due to prior treatment or natural resolution are eligible\n\nExclusion Criteria:\n\n* Secondary malignancy with documented diagnosis by a treating physician \\\u003C 3 years prior to study day -8. The following criteria also apply:\n\n  * New or progressive brain metastases. Patients with brain metastases not requiring immediate central nervous system (CNS) specific treatment or stable for at least 4 weeks prior to study day -8 are eligible at the discretion of the investigator given that neurologic symptoms are resolved.\n  * Patients with active leptomeningeal disease are not eligible\n* Palliative radiation therapy administered within 1 week prior to study day -8, Note: Participants must have recovered from all radiation-related toxicities (to grade \\\u003C 1 or baseline), must not require corticosteroids for this purpose, and must not have had radiation pneumonitis\n* Immunization with a live vaccine within 28 days prior to study day -8\n* History of organ transplantation, including hematopoietic stem cell transplantation (HSCT)\n* Clinical evidence of interstitial lung disease or active non-infectious pneumonia\n* Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (≤ 10 mg\u002Fday of prednisone or equivalent is permitted)\n* Prior National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 immune-related adverse event (irAE) that required systemic immunosuppression (endocrinopathies managed by stable doses of supplements and\u002For corticosteroids ≤ 10 mg\u002Fday are permitted)\n* Unresolved toxicities (resolution required to grade 1 or baseline) from prior anticancer therapies. The following exceptions apply:\n\n  * Alopecia, lymphopenia, grade 2 neuropathy (if not resulting in functional deficit), and grade 1 (no supplementation required) or grade 2 endocrinopathies (stable on supplements)\n* Prior allergy or severe hypersensitivity reaction to axatilimab, retifanlimab, paclitaxel, cremaphor-containing agents, and\u002For components of the drug formulations\n* Active infection requiring systemic antibiotic therapy\n* Persons of childbearing potential (PCBP) who are pregnant (i.e., positive pregnancy test within 7 days prior to study day -8) or breastfeeding are not eligible.\n\n  * The effects of the investigational regimen on the developing human fetus are unknown. For this reason, persons of reproductive potential must agree to use a highly effective form of contraception, starting with the time of consent to 4 months after the last dose of retifanlimab or 90 days after the last dose of axatilimab, whichever is longer\n  * Sperm-producing participants must not donate sperm throughout the study period and for 90 days post completion of study treatment\n* Uncontrolled, intercurrent illness and psychiatric illness\u002Fsocial situations that would limit compliance with study requirements, at the discretion of the investigator",{"count":702,"type":20},38,[65,23],"This phase I\u002FII trial tests the safety, side effects, and effectiveness of axatilimab in combination with retifanlimab and paclitaxel for the treatment of patients with a solid tumor 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). Axatilimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Giving axatilimab in combination with retifanlimab and paclitaxel may be safe, tolerable and\u002For effective in treating patients with advanced or metastatic solid tumors.",[26,32,36,268],"2025-12-25",{"date":708,"type":45},"2025-12-29",{"date":710,"type":45},"2024-05-21",{"date":460,"type":20},{"name":217,"class":218}]