[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-gastric-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-gastric-carcinoma":39},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,7,0,[8,70,99,139,194,235,291],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":58,"lastUpdatePostDateStruct":59,"startDateStruct":62,"completionDateStruct":64,"leadSponsor":66,"locationsCount":69},"100404756","phase-2-measuring-the-effects-of-talazoparib-in-patients-with-advanced-cancer-and-dna-repair-variations-100404756",false,"NCT04550494","Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations","A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response","Inclusion Criteria:\n\n* Adult patients with solid tumors and documented germline or somatic aberrations in genes involved in DNA damage response (DDR) and whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options. Molecular testing performed at an National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) (NCT02465060) study-designated Clinical Laboratory Improvement Act (CLIA) laboratory or at Myriad Genetics, GeneDx, Invitae, or the Frederick National Laboratory for Cancer Research (FNLCR) Molecular Characterization Laboratory (MoCha) will be acceptable for determination of eligibility\n* Patients with the following germline or somatic genetic aberrations will be eligible based on compelling preclinical and\u002For clinical data suggesting that these deleterious mutations confer sensitivity to PARP inhibitors; no more than 6 patients (across both cohorts) with an eligibility mutation in any one gene will be enrolled\n\n  * Deleterious BRCA1 or BRCA2 mutations\n  * Loss of function mutations (including novel loss of function frameshift or nonsense mutations) in the following Fanconi anemia genes: FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN\n  * A known functional mutation (including novel loss of function frameshift or nonsense mutations) in any of the following DDR genes: ARID1A, ATM, ATR, BACH1 (BRIP1), BAP1, BARD1, CDK12, CHK1, CHK2, IDH1, IDH2, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54L\n* Age \\>= 18 years of age\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2\n* Life expectancy of greater than 3 months\n* Leukocytes \\>= 3,000\u002FmcL\n* Absolute neutrophil count \\>= 1,500\u002FmcL\n* Platelets \\>= 100,000\u002FmcL\n* Hemoglobin \\>= 10 g\u002FdL\n* Total bilirubin =\\\u003C 1.5 x institutional upper limit of normal (=\\\u003C 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) \u002F alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 3 x institutional upper limit of normal\n* Creatinine =\\\u003C 1.5 x institutional upper limit of normal OR Creatinine clearance (CrCl) \\>= 60 mL\u002Fmin\u002F1.73m\\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL\u002Fmin\u002F1.73m\\^2\n* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \\>= 20 mm (\\>= 2 cm) by chest x-ray or as \\>= 10 mm (\\>= 1 cm) with CT scan, MRI, or calipers by clinical exam\n* Patients must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements\n* The effects of talazoparib on the developing human fetus are unknown. For this reason and because PARP inhibitors are known to be teratogenic, women of child-bearing potential must agree to use a highly effective method of contraception for the duration of study participation and for at least 7 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male patients with female partners of reproductive potential and pregnant partners who are treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and for at least 4 months after completion of talazoparib administration\n* Patients must be able to swallow whole tablets or capsules. Nasogastric or gastric-tube (G-tube) administration is not allowed. Any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed\n* Ability to understand and the willingness to sign a written informed consent document\n* Patients must have recurrent, locally advanced or metastatic disease\n* Patients must have progressed on or after at least one line of standard-of-care (SOC) intervention, except for those patients without SOC or for whom talazoparib is SOC\n* PATIENTS WITH OVARIAN CANCER:\n* All patients with ovarian cancer should have one prior platinum-based therapy\n* Patients with ovarian cancer with platinum-sensitive disease are eligible. Patients with platinum-refractory disease are not eligible\n* Patients with gBRCAm ovarian cancer must also have progressed on a PARP inhibitor. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* PATIENTS WITH PANCREATIC CANCER:\n* All patients with pancreatic cancer should have received prior platinum-containing therapy in the metastatic setting\n* PATIENTS WITH BREAST CANCER:\n* Patients with HER2+ breast cancer should have had 2 prior systemic lines of therapy in the metastatic setting, including anti-HER2 therapy\n* Patients with breast cancer who are eligible for a PARP inhibitor by Food and Drug Association (FDA) approvals must have had prior PARP inhibitor as per FDA indication. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* PATIENTS WITH GASTRIC CANCER:\n* Patients with HER2+ gastric cancer should have had received anti-HER2 therapy in the metastatic setting\n* PATIENTS WITH PROSTATE CANCER:\n* Patients with prostate cancer who are eligible for a PARP inhibitor by FDA approvals must have had prior PARP inhibitor for eligibility. The time and treatment between the prior PARP inhibitor and protocol initiation must be documented\n* All patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on prior therapy\n* Patients with castration resistant prostate cancer must have castrate levels of testosterone (\\\u003C 50 ng\u002FdL \\[1.74 nmol\u002FL\\])\n* Patients with metastatic hormone receptor (HR) prostate cancer and mutations in either BRCA1, BRCA2, or ATM should continue to receive anti-androgen receptor (anti-AR) therapy\n\nExclusion Criteria:\n\n* Patients who have had chemotherapy or radiotherapy within 4 weeks or 5 half-lives, whichever is shorter (6 weeks for nitrosoureas or mitomycin C). Patients must be \\>= 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study and be \\>= 1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events\n* Patients who have had prior treatment with talazoparib are ineligible\n* Patients who have had prior monoclonal antibody therapy must have completed that therapy \\>= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment) except for monoclonal antibody therapies that have been proven to be safe when combined with PARP inhibitor (PARPi) treatment (such as anti-PD-1\u002FPD-L1 and anti-HER2), which must be completed \\>= 4 weeks prior to enrollment\n* Patients who are receiving any other investigational agents\n* Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for \\>= 1 month without requiring steroid and anti-seizure medication are eligible to participate\n* Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of talazoparib will be determined following review by the principal investigator\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded. Low-dose warfarin (=\\\u003C 1 mg\u002Fday) is permitted\n* Women who are currently lactating\n* History of prior malignancies within the past 3 years other than non-melanomatous skin cancers that have been controlled","ALL","18 Years",{"count":19,"type":20},36,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","This phase II trial studies if talazoparib works in patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and has mutation(s) in deoxyribonucleic acid (DNA) damage response genes who have or have not already been treated with another PARP inhibitor. Talazoparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. All patients who take part on this study must have a gene aberration that changes how their tumors are able to repair DNA. This trial may help scientists learn whether some patients might benefit from taking different PARP inhibitors \"one after the other\" and learn how talazoparib works in treating patients with advanced cancer who have aberration in DNA repair genes.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Castration-Resistant Prostate Carcinoma","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","HER2-Positive Breast Carcinoma","Locally Advanced Breast Carcinoma","Locally Advanced Gastric Carcinoma","Locally Advanced Malignant Solid Neoplasm","Locally Advanced Ovarian Carcinoma","Locally Advanced Pancreatic Carcinoma","Locally Advanced Prostate Carcinoma","Metastatic Breast Carcinoma","Metastatic Gastric Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Ovarian Carcinoma","Metastatic Pancreatic Carcinoma","Metastatic Prostate Carcinoma","Platinum-Sensitive Ovarian Carcinoma","Recurrent Breast Carcinoma","Recurrent Gastric Carcinoma","Recurrent Ovarian Carcinoma","Recurrent Pancreatic Carcinoma","Recurrent Prostate Carcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage III Prostate Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","Stage IV Prostate Cancer AJCC v8","RECRUITING","2026-06-18",{"date":60,"type":61},"2026-06-22","ACTUAL",{"date":63,"type":61},"2021-04-26",{"date":65,"type":20},"2026-12-01",{"name":67,"class":68},"National Cancer Institute (NCI)","NIH",4,{"id":71,"slug":72,"hasResults":11,"nctId":73,"briefTitle":74,"officialTitle":75,"acronym":4,"eligibilityCriteria":76,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":77,"targetDuration":4,"studyType":21,"phases":79,"briefSummary":81,"conditions":82,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":93,"completionDateStruct":95,"leadSponsor":97,"locationsCount":98},"100544094","phase-1-testing-the-combination-of-the-anticancer-drugs-trastuzumab-deruxtecan-ds-8201a-and-azenosertib-zn-c3-in-patients-with-stomach-or-other-solid-tumors-100544094","NCT06364410","Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors","Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing\u002FAmplified Gastric\u002FGastroesophageal Junction Cancer and Other Solid Tumors","Inclusion Criteria:\n\n* In the dose escalation, patients must have a histologically documented locally advanced, unresectable, or metastatic solid tumor that has progressed following at least one prior line of treatment in the metastatic setting or has no satisfactory alternative treatment option and all of the following:\n\n  * HER2 expression by immunohistochemistry (IHC) (1+, 2+, or 3+) or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS) (on any Clinical Laboratory Improvements Amendments \\[CLIA\\] platform on tissue), AND\n  * T-DXd (DS-8201a)-naive disease\n* In the dose expansion, patients must have histologically documented locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer that has progressed following at least one prior line of treatment in the metastatic setting and have all of the following:\n\n  * HER2 expression by IHC (1+, 2+, or 3+) or HER2 amplification by ISH or NGS (on any CLIA platform on tissue), AND\n  * T-DXd (DS-8201a)-naive disease\n  * Received prior trastuzumab-based treatment, if eligible for such treatment\n* For the dose escalation and dose expansion, patients can have evaluable or measurable disease\n* Potential trial participants should have recovered from clinically significant adverse events (AEs) of their most recent therapy\u002Fintervention prior to enrollment\n* Age ≥ 18 years. Because no dosing or AE data are currently available on the use of T-DXd (DS-8201a) in combination with azenosertib (ZN-c3) in patients \\\u003C 18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (Karnofsky ≥ 70%). Both T-DXd (DS-8201a) and azenosertib (ZN-c3) have fatigue as an adverse effect. Due to the overlapping adverse effect, the performance status cannot be less restrictive\n* Absolute neutrophil count ≥ 1.5 × 10\\^9\u002FL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Hemoglobin \\> 9.0 g\u002FdL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Platelets ≥ 100 × 10\\^9\u002FL (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Aspartate aminotransferase (AST \\[serum glutamic-oxaloacetic transaminase (SGOT)\\])\u002Falanine aminotransferase (ALT \\[serum glutamate pyruvate transaminase (SGPT)\\]) ≤ 3 × institutional ULN. In the presence of liver metastases, AST or ALT up to 5 × institutional ULN is permitted (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Measured of calculated creatinine clearance (CrCl) ≥ 60 mL\u002Fmin (CrCl should be calculated per institutional standard; glomerular filtration rate can also be used in place of CrCl) ≥ 60 mL\u002Fmin for patients with creatinine levels \\> 1.5 x institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* International normalized ratio\u002Fprothrombin time and activated partial thromboplastin time ≤ 1.5 × institutional ULN (within 7 days of study treatment initiation)\n\n  * No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment\n  * No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment\n* Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment\n* Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first cycle of study treatment\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Life expectancy ≥ 3 months\n* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test result within 3 days of study treatment initiation\n* Agents composed of HER2 antibody conjugated to a topoisomerase 1 inhibitor and azenosertib (ZN-c3) are known to be teratogenic; thus, WOCBP must agree to use highly effective contraception from time of screening and throughout the study treatment period and for at least 7 months after final study treatment administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period and for at least 7 months after the final study treatment administration\n* Women of non-childbearing potential defined as premenopausal females with documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \\> 40 mIU\u002FmL and estradiol \\\u003C 40 pg\u002FmL \\[\\\u003C 147 pmol\u002FL\\] is confirmatory) are eligible. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for WOCBP if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their postmenopausal status, they can resume use of HRT during the study without use of a contraception method\n* Male patients involved with WOCBP must agree to use a highly effective form of contraception or avoid intercourse from time of screening and throughout the study treatment period and for at least 4 months after the last dose of study treatment. Male patients must not freeze or donate sperm starting at screening and throughout the study period and at least 4 months after the final study treatment administration. Preservation of sperm should be considered prior to enrollment in this study\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n* Willing to undergo biopsy as required by the study (dose expansion only)\n\n  * Note: Patients in the dose escalation who have insufficient\u002Finadequate archival tissue may have optional pre-treatment biopsy\n* Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery (any surgical incision should be fully healed prior to study drug administration); 4 weeks from antibody-based therapy; 2 weeks or or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); and 4 weeks from radiation therapy. These washout periods are included to ensure patients have maximal bone marrow recovery and as this is a multicenter trial, to ensure uniformity in interpretation of recovery\n\nExclusion Criteria:\n\n* As azenosertib (ZN-c3) is a substrate of CYP3A4, use of prescription or non-prescription drugs known to be moderate or strong inhibitors or inducers of CYP3A4 are prohibited with the exception of moderate or strong inhibitors or inducers of CYP3A4 that are part of the prophylactic antiemetic regimen. Chloroquine\u002Fhydroxychloroquine are metabolized by CYP3A4 and therefore, should be prohibited. For patients who have received prior moderate or strong inhibitors or inducers of CYP3A4, the required washout period is approximately 5 half-lives prior to study treatment initiation\n* Patients who are receiving any other investigational agents\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs\n* Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)\n* Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's, sarcoidosis, etc.), or prior pneumonectomy\n* Patients who require supplemental oxygen for activities of daily living\n* Pregnant women are excluded from this study because T-DXd (DS-8201a) and azenosertib (ZN-c3) have the potential risk for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with T-DXd (DS-8201a) and azenosertib (ZN-c3), breastfeeding should be discontinued if the mother is treated with T-DXd (DS-8201a) or azenosertib (ZN-c3)\n* Patients with history of non-infectious pneumonitis\u002Finterstitial lung disease (ILD), current ILD, or where suspected ILD cannot be ruled out by imaging at screening\n* Patients with active infections requiring treatment (antibiotic, antifungal, or antiviral) at the time of study treatment initiation are not eligible. Patients who have completed such treatment and whose infection is controlled\u002Fresolved (and afebrile) for at least 7 days before cycle 1 day 1 are eligible\n* Patients with history of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills\n* Patients with current signs or symptoms of bowel obstruction including sub-occlusive disease related to underlying disease\n* Patients with a medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association class IIb to IV), and\u002For troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment\n* Patients with clinically significant corneal disease\n* Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment)\n* Patients with history of Torsades de Pointes unless all risk factors that contributed to Torsades de Pointes have been corrected\n* Based on an average of triplicate 12-lead electrocardiogram (ECG), patients with a mean resting corrected QT (QTc) interval using Fridericia formula of \\> 470 msec for both males and females at screening or a history of congenital long QT syndrome will be excluded\n* Patients with prior treatment with a WEE1 inhibitor (dose escalation and dose expansion)\n* Patients with prior treatment with T-DXd (DS-8201a) or other topoisomerase inhibitors (dose escalation and dose expansion)\n* Patients with uncontrolled intercurrent illness\n* Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation\n* Patients with clinically significant chronic gastrointestinal disorder with diarrhea as a major symptom; ≥ grade 2 diarrhea at baseline. Please contact the protocol principal investigator (PI) for any patient with more than two episodes of diarrhea per day averaged over at least a 7-day period at time of screening to determine whether the diarrhea would be considered clinically significant\n* Patients with spinal cord compression",{"count":78,"type":20},48,[80],"PHASE1","This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), that have spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and\u002For more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.",[29,83,30,84,33,85,34,39,86,40,87,88,89],"Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Unresectable Gastric Carcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","Unresectable Malignant Solid Neoplasm","2026-06-16",{"date":92,"type":61},"2026-06-17",{"date":94,"type":61},"2025-02-03",{"date":96,"type":20},"2027-07-08",{"name":67,"class":68},1,{"id":100,"slug":101,"hasResults":11,"nctId":102,"briefTitle":103,"officialTitle":104,"acronym":4,"eligibilityCriteria":105,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":106,"targetDuration":4,"studyType":21,"phases":108,"briefSummary":110,"conditions":111,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":130,"startDateStruct":132,"completionDateStruct":134,"leadSponsor":136,"locationsCount":98},"100348926","intravital-microscopy-in-human-solid-tumors-100348926","NCT03823144","Intravital Microscopy in Human Solid Tumors","Intravital Microscopy (IVM) in Human Solid Tumors","Inclusion Criteria:\n\n* Age ≥ 18 years of age\n* Eastern Cooperative Oncology Group (ECOG)Performance Status of ≤ 2\n* Measurable tumor by direct visualization requiring surgical resection in the operating room (OR)\n* Tumor types of origin include gastric, pancreatic, hepatobiliary, colorectal, sarcoma, brain, or breast cancer that may involve the axillary lymph nodes cancers. Tumors may be primary or metastatic\n* Subject must understand the investigational nature of this study and sign an Independent Ethics Committee\u002FInstitutional Review Board approved written informed consent\n* Subject must have a skin prick test pre-operatively (at the time of the preoperative visit and after signed informed consent for entry into this clinical trial is given) to determine any sensitivity to fluorescein\n\nExclusion Criteria:\n\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations\n* Renal dysfunction as defined as a glomerular filtration rate (GFR) \\\u003C 45\n* Liver dysfunction as defined by Child-Pugh score \\> 5, or liver function test (LFT)'s 1.5 x above normal range\n* Any known allergy or prior reaction to fluorescein or a positive skin prick test to fluorescein\n* Pregnant or nursing female subjects, determined preoperatively with a urine pregnancy test\n* Unwilling or unable to follow protocol requirements\n* Any condition which in the investigators' opinion deems the patient unsuitable (e.g., abnormal electrocardiography \\[EKG\\], including T wave inversion, elevated T waves, prolonged QRS interval, or conduction blocks) or that requires further work-up (including cardiac echo or stress test)\n* Any condition that excludes surgical resection as the standard of care for the patient",{"count":107,"type":20},85,[109],"NA","This study will investigate the tumor-associated vasculature of patients with solid tumors. The investigators will use a technology known as intravital microscopy (IVM) in order to visualize in real-time the vessels associated with solid tumors. The IVM observations may determine if an individual patient's tumor vessels would be amenable to receiving systemic therapy, based on the functionality of the vessels.",[112,30,113,114,39,115,116,117,118,119,120,121,122,27,123,38,124,42,125,126,127,128,55],"Solid Tumor, Adult","Malignant Solid Neoplasm","Metastatic Colorectal Carcinoma","Metastatic Primary Malignant Brain Neoplasm","Metastatic Sarcoma","Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8","Resectable Colorectal Carcinoma","Resectable Liver and Intrahepatic Bile Duct Carcinoma","Resectable Pancreatic Carcinoma","Resectable Sarcoma","Stage IV Colorectal Cancer AJCC v8","Malignant Brain Neoplasm","Metastatic Liver Carcinoma","Resectable Brain Neoplasm","Resectable Breast Carcinoma","Resectable Gastric Carcinoma","Stage IV Hepatocellular Carcinoma AJCC v8","2026-05-29",{"date":131,"type":61},"2026-06-02",{"date":133,"type":61},"2019-02-28",{"date":135,"type":20},"2027-09-30",{"name":137,"class":138},"Mayo Clinic","OTHER",{"id":140,"slug":141,"hasResults":11,"nctId":142,"briefTitle":143,"officialTitle":144,"acronym":4,"eligibilityCriteria":145,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":146,"targetDuration":4,"studyType":21,"phases":148,"briefSummary":149,"conditions":150,"keywords":176,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":183,"lastUpdatePostDateStruct":184,"startDateStruct":186,"completionDateStruct":188,"leadSponsor":190,"locationsCount":193},"100561192","phase-1-a-study-with-nkt3964-for-adults-with-advancedmetastatic-solid-tumors-100561192","NCT06586957","A Study With NKT3964 for Adults With Advanced\u002FMetastatic Solid Tumors","A Phase 1, First-in-human, Open-label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-tumor Activity of the Novel Oral CDK2 Degrader NKT3964 in Adults With Advanced\u002FMetastatic Solid Tumors","Inclusion Criteria:\n\n\\- Must have a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 only: subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.\n\nDose Escalation:\n\n1. Ovarian cancer\n2. Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)\n3. Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification\n4. Small cell lung cancer (SCLC)\n5. Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)\n6. HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4\u002F6 inhibitor, and is not suitable for endocrine therapy \\[ET\\])\n7. Other solid tumors with CCNE1 amplification\n\nDose Expansion:\n\nPart 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage III) or metastatic (Stage IV); previously treated with ≥1 line of standard of care (SOC) including CDK4\u002F6 inhibitor plus ET and not suitable for further ET. Subjects must have progressed after receiving therapy for ≥3 months in the metastatic setting or for ≥6 months in the adjuvant setting. Subjects must have received ≤2 lines of systemic cytotoxic therapy (chemotherapy or cytotoxic antibody drug conjugate \\[ADC\\]) in the metastatic setting..\n\nPart 2B: Advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian\u002Ffallopian\u002Fprimary peritoneal carcinoma or clear cell ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least one platinum containing therapy and previously treated with ≤4 prior lines of systemic therapy administered for advanced\u002Fmetastatic disease and with CCNE1 amplification.\n\nPart 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy and previously treated with ≤3 prior lines of systemic therapy administered for advanced\u002Fmetastatic disease, with CCNE1 amplification as determined by NGS by local liquid or tissue test.\n\nPart 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced\u002Fmetastatic disease with CCNE1 amplification.\n\nPart 2E: Advanced\u002Frecurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug.\n\n* Have adequate organ function\n* Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception\n* Ability to swallow oral medications.\n* Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment\n\nExclusion Criteria:\n\n* Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and\u002For radiotherapy, or chemotherapy.\n* History of another malignancy with exceptions\n* History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis.\n* Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)\n* Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment\n* Known active CNS metastases and\u002For carcinomatous meningitis\n* Active interstitial lung disease currently requiring treatment\n* History of uveitis, retinopathy or other clinically significant retinal disease\n* Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease\n* Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT3964.\n* Known human immunodeficiency virus (HIV), active hepatitis B or C infection\n* Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader\n* Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder\n* Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1",{"count":147,"type":20},150,[80],"The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).",[151,152,112,153,154,155,156,41,157,158,159,160,161,162,163,164,165,166,39,167,168,169,170,171,172,173,174,175],"Solid Tumor","Advanced Solid Tumor","Metastatic Tumor","Ovarian Cancer","Ovarian Neoplasms","Ovarian Carcinoma","Endometrial Neoplasms","Endometrial Diseases","Metastatic Endometrial Cancer","Triple Negative Breast Cancer","Metastatic Endometrial Carcinoma","Advanced Endometrial Carcinoma","Advanced Ovarian Carcinoma","Gastric Cancer","Advanced Gastric Carcinoma","Metastatic Gastric Cancer","Small Cell Lung Cancer","Small Cell Lung Carcinoma","Triple Negative Breast Neoplasms","Platinum-resistant Ovarian Cancer","Platinum-refractory Ovarian Carcinoma","CCNE1 Amplification","Hormone Receptor Negative Breast Carcinoma","Human Epidermal Growth Factor 2 Negative Carcinoma of Breast","Progesterone-receptor-positive Breast Cancer",[177,178,179,180,181,182],"CDK 2 Inhibitor","CDK 4 Inhibitor","CDK 6 Inhibitor","CDK2 Degrader","Protein Degrader","PROTAC","2026-04-16",{"date":185,"type":61},"2026-04-21",{"date":187,"type":61},"2024-09-19",{"date":189,"type":20},"2029-05",{"name":191,"class":192},"NiKang Therapeutics, Inc.","INDUSTRY",19,{"id":195,"slug":196,"hasResults":11,"nctId":197,"briefTitle":198,"officialTitle":199,"acronym":4,"eligibilityCriteria":200,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":201,"targetDuration":4,"studyType":21,"phases":203,"briefSummary":204,"conditions":205,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":225,"lastUpdatePostDateStruct":226,"startDateStruct":228,"completionDateStruct":230,"leadSponsor":232,"locationsCount":234},"100387804","phase-1-pipac-for-the-treatment-of-peritoneal-carcinomatosis-in-patients-with-ovarian-uterine-appendiceal-colorectal-or-gastric-cancer-100387804","NCT04329494","PIPAC for the Treatment of Peritoneal Carcinomatosis in Patients With Ovarian, Uterine, Appendiceal, Colorectal, or Gastric Cancer","Safety and Efficacy of Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Ovarian, Uterine, Appendiceal, Colorectal, and Gastric Cancer Patients With Peritoneal Carcinomatosis (PC)","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n* Patients must have histologically confirmed ovarian, uterine, gastric, appendiceal or colorectal cancer with PC\n* Prior IP chemotherapy is permitted\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\\\u003C 2\n* Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3\n* Platelets \\>= 100,000\u002Fmm\\^3\n* Hemoglobin \\>= 9 g\u002Fdl\n* Serum total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n* Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) =\\\u003C 2.5 x ULN, unless liver metastases (Arm 1) are present or unless patients is know to have chronic liver disease (hepatitis) in which case AST and ALT must be =\\\u003C 5 x ULN\n* Alkaline phosphatase =\\\u003C 2 x ULN\n* Serum creatinine (sCr) =\\\u003C 1.5 x ULN, or creatinine clearance (Ccr) \\>= 40 ml\u002Fmin as calculated by the Cockcroft-Gault formula\n* No contraindications for a laparoscopy\n* The peritoneal disease does not have to be measurable by RECIST 1.1 but needs to be visible on cross sectional imaging or diagnostic laparoscopy\n* Patients must have progressed on at least one evidence-based chemotherapeutic regimen (Arm 1 and 2). For Arm 3, patients should have stable or responsive disease on at least 4 months first-line systemic chemotherapy\n* For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a known 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* Women of childbearing potential (WOCBP) and male patients with WOCBP partner must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is define as:\n\n  * Amenorrhea \\>= 12 consecutive months without another cause or\n  * For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level \\> 35 mIU\u002FmL\n  * Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential\n* INCLUSION TO PROCEED WITH PIPAC: Laparoscopy findings must meet all of the below criteria in order to proceed to PIPAC:\n\n  * PIPAC access is feasible\n  * There is room for aerosol therapy\n  * There is no evidence of impending bowel obstruction\n  * =\\\u003C 5 L of ascites\n  * Not a candidate for cytoreduction and HIPEC\n\nExclusion Criteria:\n\n* Gastric and colorectal\u002Fappendiceal:\n\n  * Extra-peritoneal metastatic disease\n* Arm 1 (ovarian, uterine, gastric): Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and\u002For other anthracyclines and anthracenediones\n* Arm 2 (colorectal\u002Fappendiceal): Known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency\n* Arm 2 (colorectal\u002Fappendiceal): Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy or exclusive total parenteral nutrition\n* Arm 2 (colorectal\u002Fappendiceal): Prior unanticipated severe reaction or hypersensitivity to platinum based compounds\n* Arm 2 (colorectal\u002Fappendiceal): 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, hearing loss, or non-clinically significant laboratory abnormalities. Grade 2 peripheral neuropathy is permitted\n* Arm 2 (colorectal\u002Fappendiceal): Life expectancy of less than 6 months\n* Arm 2 (colorectal\u002Fappendiceal): Chemotherapy or surgery within the last 4 weeks prior to enrollment (6 weeks for prior bevacizumab therapy). Five half-lives for other anti-cancer agents\n* Arm 2 (colorectal\u002Fappendiceal): Previous anaphylactic reaction to the chemotherapy drug used\n* Arm 2 (colorectal\u002Fappendiceal): Patients may not be receiving any other investigational or concurrent anti-cancer agents\n* Arm 2 (colorectal\u002Fappendiceal): Ascites due to decompensated liver cirrhosis; portal vein thrombosis\n* Arm 2 (colorectal\u002Fappendiceal): Simultaneous tumor debulking with gastrointestinal resection\n* Arm 2 (colorectal\u002Fappendiceal): Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias, severe renal impairment, myelosuppression, or severe hepatic impairment\n* Arm 2 (colorectal\u002Fappendiceal): Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system\n* Arm 2 (colorectal\u002Fappendiceal): Involvement in the planning and conduct of the study\n* Arm 2 (colorectal\u002Fappendiceal): Pregnancy\n* Arm 2 (colorectal\u002Fappendiceal): Patients with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Arm 2 (colorectal\u002Fappendiceal): New York Heart Association (NYHA) class 3 or 4; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months\n* Arm 2 (colorectal\u002Fappendiceal): Major systemic infection requiring antibiotics 72 hours or less prior to the first dose of study drug\n* Arm 2 (colorectal\u002Fappendiceal): Exclusive total parenteral nutrition\n* Arm 2 (colorectal\u002Fappendiceal): Prior intra-abdominal aerosol chemotherapy\n* Arm 3 (colorectal\u002Fappendiceal): Progression on first- AND second-line systemic therapy\n* Arm 3 (colorectal\u002Fappendiceal): Hematologic toxicities requiring significant dose reductions while on systemic chemotherapy\n* Arm 3 (colorectal\u002Fappendiceal): Intolerance to prior 5-FU at 2400mg\u002Fm\\^2 IV every 2 weeks or to irinotecan at 180mg\u002Fm\\^2. Intolerance is defined as the need of significant dose reduction or treatment interruption of \\> 1 week due to toxicity\n* Arm 3 (colorectal\u002Fappendiceal): Known DPD deficiency\n* Arm 3 (colorectal\u002Fappendiceal): Bowel obstruction requiring nasogastric tube, percutaneous endoscopic gastrostomy or exclusive total parenteral nutrition\n* Arm 3 (colorectal\u002Fappendiceal): 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, hearing loss, or non-clinically significant laboratory abnormalities. Grade 2 peripheral neuropathy is permitted\n* Arm 3 (colorectal\u002Fappendiceal): Life expectancy of less than 6 months\n* Arm 3 (colorectal\u002Fappendiceal): Chemotherapy or surgery within the last 2 weeks prior to enrollment (6 weeks for prior bevacizumab therapy). Five half-lives for other anti-cancer agents\n* Arm 3 (colorectal\u002Fappendiceal): Previous anaphylactic reaction to the chemotherapy drug used\n* Arm 3 (colorectal\u002Fappendiceal): Patients may not be receiving any other investigational anti-cancer agents\n* Arm 3 (colorectal\u002Fappendiceal): Ascites due to decompensated liver cirrhosis; portal vein thrombosis\n* Arm 3 (colorectal\u002Fappendiceal): Simultaneous tumor debulking with gastrointestinal resection\n* Arm 3 (colorectal\u002Fappendiceal): Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias, severe renal impairment, myelosuppression, or severe hepatic impairment\n* Arm 3 (colorectal\u002Fappendiceal): Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system\n* Arm 3 (colorectal\u002Fappendiceal): Involvement in the planning and conduct of the study\n* Arm 3 (colorectal\u002Fappendiceal): Pregnancy\n* Arm 3 (colorectal\u002Fappendiceal): Patients with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Arm 3 (colorectal\u002Fappendiceal): New York Heart Association (NYHA) class 3 or 4; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months\n* Arm 3 (colorectal\u002Fappendiceal): Major systemic infection requiring antibiotics 72 hours or less prior to the first dose of study drug\n* Arm 3 (colorectal\u002Fappendiceal): Exclusive total parenteral nutrition\n* Arm 3 (colorectal\u002Fappendiceal): Prior intra-abdominal aerosol chemotherapy",{"count":202,"type":20},49,[80],"This phase I trial studies the side effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in treating patients with ovarian, uterine, appendiceal, stomach (gastric), or colorectal cancer that has spread to the lining of the abdominal cavity (peritoneal carcinomatosis). Chemotherapy drugs, such as cisplatin, doxorubicin, oxaliplatin, leucovorin, fluorouracil, mitomycin, and irinotecan, 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. PIPAC is a minimally invasive procedure that involves the administration of intraperitoneal chemotherapy. The study device consists of a nebulizer (a device that turns liquids into a fine mist), which is connected to a high-pressure injector, and inserted into the abdomen (part of the body that contains the digestive organs) during a laparoscopic procedure (a surgery using small incisions to introduce air and to insert a camera and other instruments in the abdominal cavity for diagnosis and\u002For to perform routine surgical procedures). Pressurization of the liquid chemotherapy through the study device results in aerosolization (a fine mist or spray) of the chemotherapy intra-abdominally (into the abdomen). Giving chemotherapy through PIPAC may reduce the amount of chemotherapy needed to achieve acceptable drug concentration, and therefore potentially reduces side effects and toxicities.",[30,206,207,208,209,114,39,210,40,41,211,212,117,213,122,54,214,215,216,217,218,219,220,221,222,223,224],"Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Malignant Uterine Neoplasm","Metastatic Appendix Carcinoma","Metastatic Malignant Neoplasm in the Peritoneum","Pathologic Stage IV Gastric Cancer AJCC v8","Peritoneal Carcinomatosis","Stage IV Appendix Carcinoma AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Appendix Carcinoma AJCC v8","Stage IVA Colorectal Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Appendix Carcinoma AJCC v8","Stage IVB Colorectal Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Stage IVC Appendix Carcinoma AJCC v8","Stage IVC Colorectal Cancer AJCC v8","2025-12-03",{"date":227,"type":61},"2025-12-10",{"date":229,"type":61},"2020-08-21",{"date":231,"type":20},"2028-01-05",{"name":233,"class":138},"City of Hope Medical Center",3,{"id":236,"slug":237,"hasResults":11,"nctId":238,"briefTitle":239,"officialTitle":240,"acronym":4,"eligibilityCriteria":241,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":242,"targetDuration":4,"studyType":21,"phases":244,"briefSummary":245,"conditions":246,"keywords":4,"overallStatus":57,"whyStopped":4,"lastUpdateSubmitDate":281,"lastUpdatePostDateStruct":282,"startDateStruct":284,"completionDateStruct":286,"leadSponsor":288,"locationsCount":290},"100379539","radiation-therapy-for-the-treatment-of-metastatic-gastrointestinal-cancers-100379539","NCT04221893","Radiation Therapy for the Treatment of Metastatic Gastrointestinal Cancers","Phase II Study of Hypofractionated Radiation Therapy to Augment Immune Response in Patients With Metastatic GastroIntestinal Malignancies Progressing on Immune Therapy (ARM-GI)","Inclusion Criteria:\n\n1. Patients must have a histologically, cytologically, or radiographically confirmed metastatic gastrointestinal (GI) malignancy (esophageal, gastroesophageal, gastric, small intestine, hepatocellular, pancreaticobiliary, colorectal, or anal cancer).\n2. Patients must be receiving immunotherapy (checkpoint inhibitor or CTLA4 inhibitor) with overall response of progressive disease by RECIST criteria.\n3. Patients must have at least two metastases which are individually progressing as per RECIST criteria, one of which can be safely unirradiated as adjudicated by the treating radiation oncologist (e.g. lesions for which small increases in dimensions are unlikely to precipitate significant symptoms).\n4. Patients must have 1-5 sites of disease meeting standard-of-care indications for palliative radiation therapy as adjudicated by the treating radiation oncologist. For example:\n\n   * Symptomatic disease causing pain, bleeding, dyspnea, dysphagia, or nausea\n   * At-risk for neurologic, respiratory, cardiovascular, gastrointestinal, musculoskeletal, or hepatobiliary compromise\n5. Evaluation by a radiation oncologist within 28 days of study registration.\n6. Must have adequate organ function to administer radiation therapy and immunotherapy as per standard of care.\n7. Age \\>= 18 years.\n8. Life expectancy exceeding 6 months.\n9. Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky performance status \\>= 50.\n10. Radiation therapy is known to be teratogenic and therefore women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of radiation therapy. 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 and for 3 months after completion of radiation therapy. Contraception requirements during the follow-up period of 6 months will be according to standard of care for immunotherapy administration.\n\n    a. If a woman is of child-bearing potential, a negative pregnancy test within 28 days prior to study enrollment is required.\n11. Ability to understand a written informed consent document, and the willingness to sign it.\n\nExclusion Criteria:\n\n1. Enrollment on immunotherapy clinical trial for which radiation therapy is not permitted.\n2. Administration of radiation therapy within 4 weeks prior to study enrollment.\n3. Treatment with systemic corticosteroids or other immunosuppressive medications which would significantly diminish the effect of immunotherapy as judged by the treating physician.\n4. Radiation therapy is contraindicated as adjudicated by the radiation oncologist.",{"count":243,"type":20},28,[109],"This phase II trial studies how well radiation therapy works for the treatment of gastrointestinal cancer that are spreading to other places in the body (metastatic). Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. This trial is being done to determine if giving radiation therapy to patients who are being treated with immunotherapy and whose cancers are progressing (getting worse) can slow or stop the growth of their cancers. It may also help researchers determine if giving radiation therapy to one tumor can stimulate the immune system to attack other tumors in the body that are not targeted by the radiation therapy.",[247,248,249,250,251,252,253,254,255,256,257,258,259,114,260,39,86,261,262,263,264,211,265,266,267,268,269,270,117,271,272,273,274,275,276,277,278,122,128,216,279,220,280,224],"Stage IV Esophageal Adenocarcinoma","Stage IV Esophageal Squamous Cell Carcinoma","Stage IV Gastric Cancer","Stage IV Adenocarcinoma of the Gastroesophageal Junction","Stage IVA Esophageal Adenocarcinoma","Stage IVA Esophageal Squamous Cell Carcinoma","Stage IVA Gastric Cancer","Stage IVA Adenocarcinoma of the Gastroesophageal Junction","Stage IVB Esophageal Adenocarcinoma","Stage IVB Esophageal Squamous Cell Carcinoma","Stage IVB Gastric Cancer","Stage IVB Gastroesophageal Junction Adenocarcinoma","Metastatic Anal Canal Carcinoma","Metastatic Esophageal Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Malignant Digestive System Neoplasm","Metastatic Small Intestinal Carcinoma","Pancreatobiliary Carcinoma","Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8","Pathologic Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8","Pathologic Stage IVB Esophageal Adenocarcinoma AJCC v8","Pathologic Stage IVB Esophageal Squamous Cell Carcinoma AJCC v8","Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IV Esophageal Squamous Cell Carcinoma AJCC v8","Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Esophageal Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Esophageal Squamous Cell Carcinoma AJCC V8","Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Stage IV Anal Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","2025-09-30",{"date":283,"type":61},"2025-10-06",{"date":285,"type":61},"2020-08-07",{"date":287,"type":20},"2028-04-30",{"name":289,"class":138},"University of California, San Francisco",2,{"id":292,"slug":293,"hasResults":11,"nctId":294,"briefTitle":295,"officialTitle":296,"acronym":4,"eligibilityCriteria":297,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":298,"enrollmentInfo":299,"targetDuration":4,"studyType":21,"phases":301,"briefSummary":302,"conditions":303,"keywords":4,"overallStatus":306,"whyStopped":4,"lastUpdateSubmitDate":307,"lastUpdatePostDateStruct":308,"startDateStruct":310,"completionDateStruct":312,"leadSponsor":314,"locationsCount":98},"100591435","phase-2-node-sparing-short-course-radiotherapy-plus-first-line-therapy-and-pd-1-inhibitor-in-unresectablemetastastic-pmmrmss-gastric-cancer-modifi-gc-100591435","NCT06980389","Node-Sparing Short-Course Radiotherapy Plus First-Line Therapy and PD-1 Inhibitor in Unresectable\u002FMetastastic pMMR\u002FMSS Gastric Cancer (MODIFI-GC)","Node-Sparing Short-Course Radiotherapy Followed by First-Line Therapy Plus PD-1 Inhibitor in Unresectable Locally Advanced or Metastatic pMMR\u002FMSS Gastric Cancer: A Prospective, Randomized, Controlled Phase II Trial (MODIFI-GC)","Inclusion Criteria:\n\n* Voluntarily signs a written informed consent form.\n\n  * Aged between 18 and 75 years at the time of enrollment.\n  * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n  * Expected survival of more than 3 months.\n  * At least one measurable lesion as defined by RECIST 1.1.\n  * Histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.\n  * Tumor biopsy indicates proficient mismatch repair (pMMR) based on positive immunohistochemical staining for MSH1, MSH2, MSH6, and PMS2, or microsatellite stability (MSS) by genetic testing.\n  * No prior systemic anti-tumor therapy before study treatment, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy.\n  * Agrees to provide tumor tissue and peripheral blood samples during screening and throughout the study for research purposes.\n  * Adequate organ function as defined below:\n  * Hematologic (without blood transfusion or hematopoietic growth factor support within 7 days prior to treatment):\n  * Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹\u002FL\n  * Platelet count ≥ 100 × 10⁹\u002FL\n  * Hemoglobin ≥ 90 g\u002FL\n  * Renal:\n  * Calculated creatinine clearance (CrCl) ≥ 50 mL\u002Fmin using the Cockcroft-Gault formula:\n\nCrCl = \\[(140 - age) × weight (kg) × 0.85 (if female)\\] \u002F \\[72 × serum creatinine (mg\u002FdL)\\]\n\n* Urine protein \\\u003C 2+ by dipstick or \\\u003C 1.0 g\u002F24 h\n* Hepatic:\n* Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN)\n* AST and ALT ≤ 2.5 × ULN\n* Serum albumin ≥ 28 g\u002FL\n* Coagulation:\n* INR and APTT ≤ 1.5 × ULN\n* Cardiac:\n* Left ventricular ejection fraction (LVEF) ≥ 50%\n* Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to study treatment. If urine test is inconclusive, a serum test result shall prevail. Women of childbearing potential who are sexually active with non-sterilized male partners must agree to use an acceptable method of contraception from screening through 120 days after the last dose of study drug. Whether to discontinue contraception after this period should be discussed with the investigator. Periodic abstinence and calendar methods are not acceptable.\n* Women of childbearing potential are defined as those who have not undergone surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and who are not postmenopausal (defined as ≥12 months of amenorrhea without alternative medical cause and with serum FSH levels in the postmenopausal range).\n* Highly effective contraception methods are those with a failure rate \\\u003C1% per year when used consistently and correctly. In addition to barrier methods, hormonal contraception (e.g., oral contraceptives) must also be used.\n* Willing and able to comply with all scheduled visits, treatment plans, laboratory tests, and other study requirements.\n\nExclusion Criteria:\n\n* • Radiotherapy within 4 weeks prior to enrollment or radionuclide therapy within 8 weeks, except for palliative radiotherapy to bone metastases.\n\n  * History of other malignancies within 5 years prior to enrollment, except for those considered cured by local therapy, such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast.\n  * Gastrointestinal perforation and\u002For fistula within 6 months prior to enrollment.\n  * Clinically significant bowel obstruction.\n  * Symptomatic central nervous system (CNS) metastases.\n  * Diagnosis of HER2-positive gastric or gastroesophageal junction adenocarcinoma.\n  * Inability to swallow oral medications, malabsorption syndrome, or any other condition affecting gastrointestinal absorption.\n  * Prior systemic or local anti-tumor therapy for gastric cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, agonists, or cell therapy), biologics, or small-molecule targeted agents.\n  * Receipt of nonspecific immunomodulatory agents (e.g., interleukins, interferons, thymic peptides, tumor necrosis factor) within 2 weeks prior to study treatment (excluding IL-11 for thrombocytopenia); use of anti-tumor traditional Chinese medicine within 1 week prior to study treatment.\n  * Active autoimmune disease requiring systemic therapy within the past 2 years (e.g., corticosteroids, immunosuppressants, DMARDs). Replacement therapy (e.g., thyroid hormone, insulin, or physiologic corticosteroids for adrenal\u002Fpituitary insufficiency) is permitted.\n  * History of or current interstitial lung disease or non-infectious pneumonitis requiring systemic corticosteroids.\n  * History of significant bleeding disorders or coagulopathy; current or prior long-term anticoagulation (e.g., atrial fibrillation with CHADS2 score ≥ 2).\n  * Uncontrolled comorbidities including, but not limited to, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer or gastritis, or psychiatric\u002Fsocial conditions interfering with protocol compliance or informed consent.\n  * History of myocarditis, cardiomyopathy, or malignant arrhythmia; unstable angina, heart failure requiring hospitalization, or vascular disease (e.g., aortic aneurysm requiring repair or DVT) within 12 months before treatment; other cardiac conditions that may interfere with safety evaluation, such as poorly controlled arrhythmias, myocardial infarction, or ischemia.\n  * Within 6 months prior to treatment: gastroesophageal varices, severe ulcers, unhealed wounds, GI perforation, fistula, intestinal obstruction, intra-abdominal abscess, or acute GI bleeding.\n  * Arterial thromboembolism, grade ≥3 venous thromboembolism (per NCI CTCAE v5.0), TIA, stroke, hypertensive crisis, or hypertensive encephalopathy within 6 months before treatment.\n  * Acute exacerbation of COPD within 1 month prior to treatment; uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite oral therapy).\n  * Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or chronic diarrhea.\n  * Serious infection within 4 weeks prior to treatment, including those requiring hospitalization, sepsis, or severe pneumonia; active systemic infection requiring anti-infective therapy within 10 days before treatment (excluding antiviral therapy for HBV or HCV).\n  * Major surgery or significant trauma within 30 days prior to treatment; minor local surgery within 3 days prior (excluding central venous catheter placement via peripheral vein).\n  * History of immunodeficiency; HIV antibody positive; long-term use of systemic corticosteroids or immunosuppressants.\n  * Known active tuberculosis (TB), or suspected active TB not ruled out by clinical assessment (e.g., sputum testing, chest imaging); known active syphilis.\n  * History of allogeneic organ or hematopoietic stem cell transplantation.\n  * Untreated active hepatitis B infection (HBsAg positive and HBV DNA \\> 1,000 copies\u002FmL or 200 IU\u002FmL); patients with HBV must receive antiviral therapy during the study. Active hepatitis C infection (HCV antibody positive with detectable HCV RNA) is also excluded.\n  * Receipt of a live vaccine within 30 days prior to treatment or planned during the study period.\n  * Known allergy to any component of study drugs or history of severe hypersensitivity to monoclonal antibodies.\n  * Known history of psychiatric disorders, substance abuse, alcoholism, or drug addiction.\n  * Pregnant or breastfeeding women.\n  * Any condition, treatment, or abnormal laboratory findings that may confound study results, interfere with study participation, or not be in the best interest of the participant.\n  * Local or systemic disease caused by benign tumors, or tumor-related complications with high medical risk or uncertain prognosis (e.g., leukemoid reaction with WBC \\> 20 × 10⁹\u002FL, cachexia with \\>10% weight loss in 3 months before screening, or BMI ≤ 18).","75 Years",{"count":300,"type":20},176,[23],"For patients with unresectable locally advanced or metastatic gastric cancer, systemic anti-tumor therapy remains the mainstay of treatment. Combining chemotherapy with immune checkpoint inhibitors has gradually become the standard first-line treatment for advanced gastric cancer. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of MSS\u002FpMMR tumors to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for the anti-tumor activity of PD-1 blockade; however, radiation-induced damage and fibrosis may impair lymphatic drainage and local immune responses. Previous studies have suggested that irradiation of the primary tumor combined with immune checkpoint blockade can produce an abscopal effect, mediating regression of distant metastases. This study aims to evaluate whether node-sparing modified short-course radiotherapy followed by chemotherapy and PD-1 blockade can improve 2-year progression-free survival (PFS) in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.",[304,305,39],"Immune Checkpoint Therapy","Radiotherapy","NOT_YET_RECRUITING","2025-05-12",{"date":309,"type":61},"2025-05-20",{"date":311,"type":20},"2025-05-31",{"date":313,"type":20},"2028-12-31",{"name":315,"class":138},"Sixth Affiliated Hospital, Sun Yat-sen University"]