[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-gastroesophageal-junction-adenocarcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-gastroesophageal-junction-adenocarcinoma":39},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,14,0,[8,56,85,96,116,232,255,280,328,363,383,433,455,468],{"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":25,"conditions":26,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":44,"lastUpdatePostDateStruct":45,"startDateStruct":48,"completionDateStruct":50,"leadSponsor":52,"locationsCount":55},"100053222","phase-2-adding-nivolumab-to-usual-treatment-for-people-with-advanced-stomach-or-esophageal-cancer-paramune-trial-100053222",false,"NCT06203600","Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial","Randomized Phase II\u002FIII Trial of 2nd Line Nivolumab + Paclitaxel + Ramucirumab Versus Paclitaxel + Ramucirumab in Patients With PD-L1 CPS >\u002F= 1 Advanced Gastric and Esophageal Adenocarcinoma (PARAMUNE)","Inclusion Criteria:\n\n* Participants must have advanced or locally unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma\n* Participants must have PD-L1 CPS (Combined Positive Score) ≥ 1. This test would have been performed as part of standard of care (SOC) pathology testing, using tissue obtained within two years prior to registration and collected prior to or after a frontline regimen\n* Participants must have a histologically confirmed diagnosis of microsatellite stable (MSS) and HER2 negative gastric, gastroesophageal junction, or esophageal adenocarcinoma\n* Participants must have documented unresectable and\u002For metastatic disease on CT or MRI imaging completed prior to registration. Imaging must have been completed within 28 days prior to registration for participants with measurable disease. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form\n* Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy. All treatment for brain metastases must have been completed at least 28 days prior to registration\n* Participants must have disease progression or intolerance to frontline standard of care (SOC) chemotherapy plus either nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor. Peri-operative chemotherapy plus nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor will count as one line if disease progression occurs while on the therapy or within 6 months of completing the chemotherapy plus nivolumab or pembrolizumab or other PD-1\u002FPD-L1 inhibitor cycle\n* Participants must not have received more than one prior line of systemic therapy defined as chemotherapy plus either nivolumab, pembrolizumab, or any other PD-1 or PD-L1 inhibitor, in the stage IV or unresectable setting. Peri-operative or adjuvant nivoluamb or other PD-1\u002FPD-L1 inhibitors would count as one prior line of systemic therapy if patients progressed while on nivolumab (or other PD-1\u002FPD-L1 inhibitors) or within 6 months of stopping it\n\n  * Note: Radiation or any other regional therapy options done to address local residual disease or metastatic disease would not count as a line of therapy. Maintenance therapy with a different form of fluoropyrimidine (i.e. switching from capecitabine to fluorouracil \\[5FU\\]) would not count as another line of therapy\n* Participants must not have a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses \\\u003C 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \\\u003C 10 mg\u002Fday prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of ≥ 7 days prior to registration\n* Participants must not have prior significant immunotherapy related adverse events requiring permanent discontinuation of the immunotherapy agent including events like pneumonitis, myocarditis, renal failure, Guillain barre syndrome, or myasthenia gravis. Participants with endocrinopathy events leading or not to replacement steroids, thyroid hormone, insulin, or cortisol are eligible\n* Participants must not have received a live attenuated vaccination within 28 days prior to registration\n* Participants must not have had a major surgery within 28 days or subcutaneous venous access device placement within 7 days prior registration\n* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator. Any participants with postoperative bleeding complications or wound complications from a surgical procedure performed in the last eight weeks should be excluded\n* Participants must not have plans to undergo elective or planned major surgery during the clinical trial\n* Participants must not have active bleeding or prior history of gastrointestinal (GI) perforation, fistula or significant GI bleeding (requiring transfusion, endoscopic or surgical intervention) within 84 days prior to registration\n* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, investigational agents, biologic or hormonal therapy for cancer treatment while receiving treatment on this study\n* Participants must not have a history of a grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy\n* Participants must not have a history of grade 3 or 4 immunotherapy related toxicities with the exception of hormonal abnormalities like thyroiditis or thyroid derangements\n* Participants must be ≥ 18 years old\n* Participants must have Zubrod Performance Status of 0-2\n* Participants must have a complete medical history and physical exam within 28 days prior to registration\n* Leukocytes ≥ 2 x 10\\^3\u002FuL (within 28 days prior to registration)\n* Absolute neutrophil count ≥ 1.2 x 10\\^3\u002FuL (within 28 days prior to registration)\n* Hemoglobin ≥ 9.0 g\u002FdL (within 28 days prior to registration)\n* Platelets ≥ 100 x 10\\^3\u002FuL (within 28 days prior to registration)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤ 3 × institutional ULN (within 28 days prior to registration) (unless liver metastases are present, in which case they must be ≤ 5 x ULN)\n* Participants must have a calculated creatinine clearance ≥ 40 mL\u002Fmin using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration\n* Participants' urinary protein must be ≤ 1+ on dipstick or routine urinalysis (UA) within 28 days of registration. Random analysis of urine protein with a normal value is sufficient. If urine dipstick or routine analysis indicated proteinuria ≥ 2+, then a 24-hour urine is to be collected and demonstrate \\\u003C 1000 mg of protein in 24 hours to allow participation in the study\n* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better\n* Participants must have recovered to baseline or \\\u003C grade 2 CTCAE version (v) 5.0 from toxicities related to any prior treatments, unless AE(s) are clinically stable on supportive therapy\n* Participants must not have experienced arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to registration\n* Participants must not have uncontrolled blood pressure within 28 days prior to registration as determined by the treating investigator\n* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load on the most recent test results obtained within 6 months prior to registration\n* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated\n* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load on the most recent test results obtained within 6 months prior to registration, if indicated\n* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of \"reproductive potential.\" In addition to routine contraceptive methods, \"effective contraception\" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation\u002Focclusion, and vasectomy with testing showing no sperm in the semen\n* Participants must not have a history of inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \\[scleroderma\\], systemic lupus erythematosus, autoimmune vasculitis \\[e.g., Wegener's Granulomatosis\\]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis). Note: Participants with Graves' disease will be allowed\n* Participants must not have a history of pneumonitis that has required oral or IV steroids within the last 12 months prior to registration\n* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System\n* Participants who can complete patient reported outcomes (FACT-Ga and PRO-CTCAE) questionnaires in English or Spanish must participate in the quality of life studies\n* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations","ALL","18 Years",{"count":19,"type":20},224,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE2","PHASE3","This phase II\u002FIII trial compares the addition of nivolumab to the usual treatment of paclitaxel and ramucirumab to paclitaxel and ramucirumab alone in treating patients with gastric or esophageal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with 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. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Adding nivolumab to ramucirumab and paclitaxel may work better to treat patients with advanced stomach or esophageal cancer.",[27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42],"Advanced Esophageal Adenocarcinoma","Advanced Gastric Adenocarcinoma","Advanced Gastroesophageal Junction Adenocarcinoma","Clinical Stage II Esophageal Adenocarcinoma AJCC v8","Clinical Stage III Esophageal Adenocarcinoma AJCC v8","Clinical Stage III Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Esophageal Adenocarcinoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Metastatic Esophageal Adenocarcinoma","Metastatic Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Unresectable Esophageal Adenocarcinoma","Unresectable Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","RECRUITING","2026-07-10",{"date":46,"type":47},"2026-07-13","ACTUAL",{"date":49,"type":47},"2024-06-24",{"date":51,"type":20},"2027-10-31",{"name":53,"class":54},"National Cancer Institute (NCI)","NIH",372,{"id":57,"slug":58,"hasResults":11,"nctId":59,"briefTitle":60,"officialTitle":61,"acronym":4,"eligibilityCriteria":62,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":63,"enrollmentInfo":64,"targetDuration":4,"studyType":21,"phases":66,"briefSummary":67,"conditions":68,"keywords":70,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":75,"lastUpdatePostDateStruct":76,"startDateStruct":77,"completionDateStruct":79,"leadSponsor":81,"locationsCount":84},"100054242","phase-2-docetaxel-oxaliplatin-and-5-fu-for-gastric-cancer-with-inoperable-malignant-bowel-obstruction-100054242","NCT04840264","Docetaxel, Oxaliplatin and 5-FU for Gastric Cancer With Inoperable Malignant Bowel Obstruction","A Multi-center, Non-randomized, Three-cohort, Phase II Trial of a Modified Triplet Combination of Docetaxel, Oxaliplatin and Fluorouracil for Gastric Cancer With Peritoneal Carcinomatosis and Inoperable Malignant Bowel Obstruction","Inclusion Criteria:\n\n* 18-75 years of age;\n* ECOG PS ≤3;\n* pathologically diagnosed gastric or gastroesophageal junctional adenocarcinoma;\n* peritoneal carcinomatosis established by imaging data or pathological evidence;\n* MBO below the Treitz ligament based on clinical grounds or radiological findings;\n* considered as inoperable MBO by two independent surgical consultants;\n* Hb≥60g\u002FL, WBC ≥4×10E9\u002FL, ANC≥2×10E9\u002FL，PLT≥100×10E9\u002FL;\n* Cr≤ Upper Normal Limit(UNL);\n* Tbil≤1.5 UNL,AST≤1.5 UNL, ALT≤1.5 UNL, ALP≤1.5 UNL;\n* Written informed consent form paticipants.\n\nExclusion Criteria:\n\n* treated by a combination regimen containing all the study drugs;\n* allergy to any of the study drugs;\n* HER-2 amplification or overexpression, mismatch repair protein expression deletion (dMMR), or genetic testing suggestive of high microsatellite instability (MSI-H);\n* strangulated intestinal obstruction;\n* active gastrointestinal bleeding;\n* uncontrolled active infection;\n* unstable heart diseases with severe ECG abnormalities or affect clinical treatment (such as cardiac insufficiency, myocardial infarction, angina);\n* severe lung diseases (such as interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc);\n* mental disorders that affect clinical treatment or central nervous system diseases;\n* concomitant cerebral parenchymal or meningeal metastasis;\n* HIV infection or untreated active hepatitis;\n* bowel surgery or stenting required due to obstruction;\n* pregnant or lactating women;\n* other conditions that are not suitable for participation in the study.","75 Years",{"count":65,"type":20},79,[23],"This is a multi-center, non-randomized, 3-cohort, phase II trial, evaluating a triplet combination of docetaxel, oxaliplatin and fluorouracil for gastric cancer with peritoneal carcinomatosis and inoperable malignant bowel obstruction.",[38,39,69],"Peritoneal Carcinomatosis",[71,72,73,74],"Malignant Bowel Obstruction","Docetaxel","Oxaliplatin","Fluorouracil","2026-07-09",{"date":46,"type":47},{"date":78,"type":47},"2022-01-07",{"date":80,"type":20},"2028-06-30",{"name":82,"class":83},"Sixth Affiliated Hospital, Sun Yat-sen University","OTHER",1,{"id":86,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":87,"targetDuration":4,"studyType":21,"phases":88,"briefSummary":25,"conditions":89,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":93,"completionDateStruct":94,"leadSponsor":95,"locationsCount":55},"100531730",{"count":19,"type":20},[23,24],[27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42],"2026-07-01",{"date":92,"type":47},"2026-07-02",{"date":49,"type":47},{"date":51,"type":20},{"name":53,"class":54},{"id":97,"slug":98,"hasResults":11,"nctId":99,"briefTitle":100,"officialTitle":101,"acronym":4,"eligibilityCriteria":102,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":103,"targetDuration":4,"studyType":21,"phases":105,"briefSummary":106,"conditions":107,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":108,"startDateStruct":109,"completionDateStruct":111,"leadSponsor":113,"locationsCount":115},"100491312","phase-3-mfolfirinox-versus-mfolfox-with-or-without-nivolumab-for-the-treatment-of-advanced-unresectable-or-metastatic-her2-negative-esophageal-gastroesophageal-junction-and-gastric-adenocarcinoma-100491312","NCT05677490","mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma","Randomized Phase III Trial of mFOLFIRINOX vs. FOLFOX With Nivolumab for First-Line Treatment of Metastatic HER2- Gastroesophageal Adenocarcinoma","Inclusion Criteria:\n\n* Histologic documentation: HER2 negative adenocarcinoma as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (Bartley et al., Journal of Clinical Oncology \\[JCO\\] 2017) with known PD-L1 CPS (Any CPS is allowed, but should be known prior to registration)\n* Stage: unresectable or metastatic\n* Tumor site: esophagus, gastroesophageal junction, or stomach\n* Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n* No prior treatment for unresectable or metastatic disease\n* Prior neoadjuvant or adjuvant cytotoxic chemotherapy or adjuvant immunotherapy is allowed as long as it was completed at least 1 year prior to registration\n* Age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1\n* Absolute neutrophil count (ANC) \\>= 1,500\u002Fmm\\^3\n* Platelet count \\>= 100,000\u002Fmm\\^3\n* Creatinine =\\\u003C 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \\>= 30 mL\u002Fmin\n* Total bilirubin =\\\u003C 1.5 x ULN\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 3 x ULN (in patients with liver metastasis: =\\\u003C 5 x ULN if clearly attributable to liver 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 positive for human immunodeficiency virus (HIV) are eligible only if they meet all of the following:\n\n  * On effective anti-retroviral therapy\n  * Undetectable HIV viral load by standard clinical assay =\\\u003C 6 months of registration\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* Patients who will receive nivolumab in addition to chemotherapy must not have any contraindications to immune checkpoint inhibitors\n\n  * Patients must not have active autoimmune disease that has required systemic treatment within 6 months prior to registration. Patients are permitted to receive immunotherapy if they have vitiligo, type I diabetes, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)\n  * Patients must not have a condition requiring systemic treatment with either corticosteroids (\\>10mg\u002Fday prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses (=\\\u003C 10mg\u002Fday prednisone equivalent) are permitted\n  * Patients must not have a history of noninfectious pneumonitis requiring steroids\n  * Patients with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents are ineligible\n* This study includes the use of the mandatory patient completed measure, PRO-CTCAE. For this study the PRO-CTCAE is available in English, Spanish, Korean, Chinese (Simplified), and Russian, hence patients must be able to speak, understand and read in these languages. Ad-hoc translation of patient-reported measures is not permitted\n\nExclusion Criteria:\n\n* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects\n\n  \\* Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =\\\u003C 7 days prior to registration is required\n* No known Gilbert's syndrome or known homozygosity for UGAT1A1\\*28 polymorphism\n* No baseline grade \\>= 2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per CTCAE version (v) 5.0 regardless of causality\n* No medical condition such as uncontrolled infection or uncontrolled diabetes mellitus which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient\n* No untreated, symptomatic brain metastasis. Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose for more than four weeks\n* No allogeneic tissue\u002Forgan transplant",{"count":104,"type":20},382,[24],"This phase III trial compares the effect of modified fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) for the treatment of advanced, unresectable, or metastatic HER2 negative esophageal, gastroesophageal junction, and gastric adenocarcinoma. The usual approach for patients is treatment with FOLFOX chemotherapy. Chemotherapy drugs 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. Fluorouracil stops cells from making DNA and it may kill tumor cells. Leucovorin is used with fluorouracil to enhance the effects of the drug. Oxaliplatin works by killing, stopping, or slowing the growth of tumor cells. Some patients also receive an immunotherapy drug, nivolumab, in addition to FOLFOX chemotherapy. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Irinotecan blocks certain enzymes needed for cell division and DNA repair, and it may kill tumor cells. Adding irinotecan to the FOLFOX regimen could shrink the cancer and extend the life of patients with advanced gastroesophageal cancers.",[27,28,29,31,32,33,34,35,36,37,38,39,40,41,42],{"date":92,"type":47},{"date":110,"type":47},"2023-01-31",{"date":112,"type":20},"2028-11-08",{"name":114,"class":83},"Alliance for Clinical Trials in Oncology",794,{"id":117,"slug":118,"hasResults":11,"nctId":119,"briefTitle":120,"officialTitle":121,"acronym":122,"eligibilityCriteria":123,"healthyVolunteers":11,"sex":16,"minAge":124,"maxAge":4,"enrollmentInfo":125,"targetDuration":4,"studyType":21,"phases":127,"briefSummary":129,"conditions":130,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":223,"lastUpdatePostDateStruct":224,"startDateStruct":226,"completionDateStruct":228,"leadSponsor":230,"locationsCount":84},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol\n\n  * NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test =\\\u003C 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained =\\\u003C 28 days prior to pre-registration:\n\n  * Hemoglobin \\>= 9.0 g\u002FdL (Must be \\>= 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 or \\>= 1.5 X 10\\^9\u002FL\n  * Platelet count \\>= 100,000\u002Fmm\\^3 or \\>= 100 X 10\\^9\u002FL (Must be \\>=7 days after most recent transfusion)\n  * Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) =\\\u003C 3 x ULN or =\\\u003C 5 x ULN with liver metastases\n  * Creatinine =\\\u003C 1.5 x ULN OR calculated creatinine clearance must be \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see specified limits for inclusion) or NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease \\>= 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor \\>= 2 cm on pre-surgery evaluation imaging (residual disease \\>= 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to proceed with surgery and provide tissue specimens for complete exome and transcriptome sequencing\n\n  * NOTE: Patients who had sequencing under certain Mayo IRB protocols and neoantigens identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test ≤7 days prior to pre-registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive \\>= 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction =\\\u003C 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke =\\\u003C 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in =\\\u003C 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major Surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n  * Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002Fribonucleic acid (RNA)\u002Fdeoxyribonucleic acid (DNA) quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are \\>= 2 cores with passing cellularity; (3) \\>= 30% of tumor RNA with fragment sizes are \\>= 200 base pairs (DV200 \\>= 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Requirement for systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in","16 Years",{"count":126,"type":20},132,[128,23],"PHASE1","This phase I\u002FII trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.",[131,132,133,134,135,136,32,33,137,138,35,36,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,38,39,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,41,42,208,209,210,211,212,213,214,215,216,217,218,219,220,221,222],"Anatomic Stage III Breast Cancer AJCC v8","Anatomic Stage IIIA Breast Cancer AJCC v8","Anatomic Stage IIIB Breast Cancer AJCC v8","Anatomic Stage IIIC Breast Cancer AJCC v8","Anatomic Stage IV Breast Cancer AJCC v8","Clinical Stage III Cutaneous Melanoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Lung Non-Small Cell Carcinoma","Locally Advanced Malignant Solid Neoplasm","Locally Advanced Melanoma","Locally Advanced Merkel Cell Carcinoma","Locally Advanced Renal Cell Carcinoma","Locally Advanced Skin Squamous Cell Carcinoma","Locally Advanced Triple-Negative Breast Carcinoma","Locally Advanced Unresectable Breast Carcinoma","Locally Advanced Unresectable Cervical Carcinoma","Locally Advanced Unresectable Gastric Adenocarcinoma","Locally Advanced Unresectable Gastroesophageal Junction Adenocarcinoma","Locally Advanced Unresectable Renal Cell Carcinoma","Locally Advanced Urothelial Carcinoma","Metastatic Cervical Carcinoma","Metastatic Endometrial Carcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Melanoma","Metastatic Merkel Cell Carcinoma","Metastatic Renal Cell Carcinoma","Metastatic Skin Squamous Cell Carcinoma","Metastatic Triple-Negative Breast Carcinoma","Metastatic Urothelial Carcinoma","Skin Squamous Cell Carcinoma","Stage III Cervical Cancer AJCC v8","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IIIA Cervical Cancer AJCC v8","Stage IIIA Hepatocellular Carcinoma AJCC v8","Stage IIIA Lung Cancer AJCC v8","Stage IIIA Uterine Corpus Cancer AJCC v8","Stage IIIB Cervical Cancer AJCC v8","Stage IIIB Hepatocellular Carcinoma AJCC v8","Stage IIIB Lung Cancer AJCC v8","Stage IIIB Uterine Corpus Cancer AJCC v8","Stage IIIC Lung Cancer AJCC v8","Stage IIIC Uterine Corpus Cancer AJCC v8","Stage IIIC1 Uterine Corpus Cancer AJCC v8","Stage IIIC2 Uterine Corpus Cancer AJCC v8","Stage IV Cervical Cancer AJCC v8","Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","Stage IVA Cervical Cancer AJCC v8","Stage IVA Hepatocellular Carcinoma AJCC v8","Stage IVA Lung Cancer AJCC v8","Stage IVA Uterine Corpus Cancer AJCC v8","Stage IVB Cervical Cancer AJCC v8","Stage IVB Hepatocellular Carcinoma AJCC v8","Stage IVB Lung Cancer AJCC v8","Stage IVB Uterine Corpus Cancer AJCC v8","Triple-Negative Breast Carcinoma","Unresectable Cervical Carcinoma","Unresectable Endometrial Carcinoma","Unresectable Head and Neck Squamous Cell Carcinoma","Unresectable Hepatocellular Carcinoma","Unresectable Lung Non-Small Cell Carcinoma","Unresectable Malignant Solid Neoplasm","Unresectable Melanoma","Unresectable Merkel Cell Carcinoma","Unresectable Renal Cell Carcinoma","Unresectable Skin Squamous Cell Carcinoma","Unresectable Triple-Negative Breast Carcinoma","Unresectable Urothelial Carcinoma","Breast Adenocarcinoma","Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8","Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8","2026-06-18",{"date":225,"type":47},"2026-06-23",{"date":227,"type":47},"2022-03-31",{"date":229,"type":20},"2028-03-31",{"name":231,"class":83},"Mayo Clinic",{"id":233,"slug":234,"hasResults":11,"nctId":235,"briefTitle":236,"officialTitle":237,"acronym":4,"eligibilityCriteria":238,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":239,"targetDuration":4,"studyType":21,"phases":241,"briefSummary":242,"conditions":243,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":247,"lastUpdatePostDateStruct":248,"startDateStruct":250,"completionDateStruct":252,"leadSponsor":254,"locationsCount":84},"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":240,"type":20},48,[128],"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.",[32,33,35,36,244,147,151,245,39,168,246,42,211],"Locally Advanced Gastric Carcinoma","Metastatic Gastric Carcinoma","Unresectable Gastric Carcinoma","2026-06-16",{"date":249,"type":47},"2026-06-17",{"date":251,"type":47},"2025-02-03",{"date":253,"type":20},"2027-07-08",{"name":53,"class":54},{"id":256,"slug":257,"hasResults":11,"nctId":258,"briefTitle":259,"officialTitle":260,"acronym":4,"eligibilityCriteria":261,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":262,"targetDuration":4,"studyType":21,"phases":264,"briefSummary":265,"conditions":266,"keywords":4,"overallStatus":269,"whyStopped":4,"lastUpdateSubmitDate":270,"lastUpdatePostDateStruct":271,"startDateStruct":273,"completionDateStruct":275,"leadSponsor":277,"locationsCount":279},"100638988","phase-1-futibatinib-with-paclitaxel-and-ramucirumab-for-the-treatment-of-locally-advanced-or-unresectable-gastric-gastroesophageal-junction-or-esophageal-adenocarcinoma-100638988","NCT07594548","Futibatinib With Paclitaxel and Ramucirumab for the Treatment of Locally Advanced or Unresectable Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma","A Phase I\u002FIb Dose Escalation Trial of Futibatinib in Combination With Paclitaxel\u002FRamucirumab in Second Line Confirmed Locally Advanced\u002FUnresectable Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed locally advanced\u002Funresectable gastric, gastroesophageal junction, or esophageal adenocarcinoma that is microsatellite stable and HER2 negative. (American Joint Committee on Cancer \\[AJCC\\] staging criteria; https:\u002F\u002Fpmc.ncbi.nlm.nih.gov\u002Farticles\u002FPMC5387145\u002F)\n\n  * Note: Histological or cytological test reports from external laboratories outside of Northwestern University (NU) will also be accepted\n* Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\n  * Note: Patients must have documented unresectable and\u002For metastatic disease on CT or MRI imaging completed prior to registration. Imaging must have been completed within 90 days prior to registration for participants with measurable disease\n* Patients must not have received more than 1 prior line of therapy in the metastatic setting.\n\n  * Note: Patients who have received neoadjuvant or adjuvant therapy must have completed therapy a year prior to registration in this study. Exception: patients with neoadjuvant or adjuvant therapy who have progressed within 6 months\n* Patients must be age ≥ 18 years\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Leukocytes (white blood cells \\[WBC\\]) ≥ 2,000\u002FmcL\n* Absolute neutrophil count (ANC) ≥ 1500\u002FmcL\n* Hemoglobin (Hgb) ≥ 9 g\u002FdL (transfusions within 1 week of registration are not allowed to meet cutoff)\n* Platelets (PLT) ≥ 100,000\u002FmcL (transfusions within 1 week of registration are not allowed to meet cutoff)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) ≤ 3 x institutional ULN (unless liver metastases are present, in which case they must be ≤ 5 x ULN)\n* Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional ULN (unless liver metastases are present, in which case they must be ≤ 5 x ULN)\n* Creatinine ≤ 1.5 x Institutional ULN or meeting creatinine clearance (CrCl) criteria below\n* Creatinine clearance per the Cockcroft-Gault formula or 24-hour urine collection) ≥ 45 mL\u002Fmin\n* Phosphate \\\u003C ULN\n* International normalized ratio (INR) \\\u003C 1.5\n* Patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA) within 28 days of registration.\n\n  * Note: Random analysis of urine protein with a normal value is sufficient. If urine dipstick or routine analysis indicated proteinuria ≥ 2+, then a 24-hour urine is to be collected and demonstrate \\\u003C 1000 mg of protein in 24 hours to allow participation in the study\n* For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration.\n\n  * Please note: this lab is not a requirement for eligibility, however, if it has been completed previously as part of the patient's health care, it should be documented for eligibility\n* Patients with known history of chronic hepatitis B virus (HBV) infection must be on suppressive therapy with an undetectable viral load.\n\n  * Please note: this lab is not a requirement for eligibility, however if it has been completed previously as part of the patient's health care, it should be documented for eligibility\n* Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with a known HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load.\n\n  * Please note: this lab is not a requirement for eligibility, however if it has been completed previously as part of the patient's health care, it should be documented for eligibility\n* Patients with treated brain metastases must not have any evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy.\n\n  * Note: All treatment for brain metastases must have been completed at least 28 days prior to registration\n* Futibatinib and other therapeutic agents used in this trial are known to be teratogenic. For this reason, patients of child-bearing potential (POCBP) and their partners with sperm-producing reproductive capacity must agree to use adequate contraception from time of informed consent, for the duration of study participation, and for 3 months following completion of study drug therapy. Should a POCBP become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must also agree to use adequate contraception with partners of childbearing potential from time of informed consent, for the duration of study participation, and 3 months after completion of study drug administration\n\n  * Note: A POCBP is any patient (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) with an egg-producing reproductive tract who meets the following criteria:\n  * Has not undergone a hysterectomy or bilateral oophorectomy\n  * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months)\n* POCBP must have a negative pregnancy test prior to registration on study\n* Patients must have the ability to understand and the willingness to sign a written informed consent document and comply with the study requirements\n* Patients must have the ability to swallow, retain and absorb oral medications\n\nExclusion Criteria:\n\n* Patients with adenosquamous or mixed histology disease\n* Patients who have received\u002Fare receiving other investigational agents, or anticancer\u002Fantineoplastic therapy including chemotherapy, immunotherapy, biological response modifiers, anti-neoplastic endocrine therapy or devices concurrently or within 21 days or 5 times the half-life, whichever is shorter, prior to first dose of cycle 1\n* Patients who have previously received a FGFR inhibitor.\n\n  * Note: Agents that are multi-kinase inhibitors are allowed\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia, neuropathy and other non-significant adverse events per NCI CTCAE v 6.0\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, ramucirumab, or futibatinib\n* Patients who have major surgical procedure planned during the study or any surgery within 28 days of registration or any subcutaneous venous access device placement within 7 days prior registration\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, or who have experienced arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to registration ,should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.\n\n  * Note: To be eligible for this trial, patients should be class 2B or better\n* History of gastrointestinal perforation and\u002For fistulae within 6 months prior to registration\n* History of active bleeding or significant gastrointestinal (GI) bleeding requiring intervention within 60 days prior to registration\n* History and\u002For current evidence of endocrine alteration of calcium-phosphorus homeostasis. History and\u002For current evidence of ectopic mineralization\u002Fcalcification including but not limited to soft tissue, kidneys, intestine, or myocardia and lung with the exception of calcified lymph nodes and asymptomatic arterial calcification\n* Current evidence of retinal disorder\u002Fkeratopathy including but not limited to bullous\u002Fband keratopathy, corneal abrasion, inflammation\u002Fulceration, keratoconjunctivitis, etc., confirmed by ophthalmologic examination\n* Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:\n\n  * Hypertension that is not controlled on medication(per treating physician's discretion)\n  * Ongoing or active infection requiring systemic treatment\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Cardiac arrhythmia\n  * Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints\n* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or activity assessment of the investigational regimen (per treating physician's discretion)\n* Patients who are pregnant or nursing",{"count":263,"type":20},18,[128],"This phase I trial tests the safety, side effects and best dose of futibatinib with paclitaxel and ramucirumab for the treatment of patients with gastric, gastroesophageal junction or esophageal adenocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced) or that cannot be removed by surgery (unresectable). Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving futibatinib with paclitaxel and ramucirumab may be safe and tolerable in treating patients with locally advanced or unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma.",[30,31,32,33,34,35,36,267,146,147,37,38,39,40,41,268],"Locally Advanced Esophageal Adenocarcinoma","Unresectable Gastroesophageal Junction Carcinoma","NOT_YET_RECRUITING","2026-05-13",{"date":272,"type":47},"2026-05-18",{"date":274,"type":20},"2027-09-09",{"date":276,"type":20},"2031-09-09",{"name":278,"class":83},"Northwestern University",2,{"id":281,"slug":282,"hasResults":11,"nctId":283,"briefTitle":284,"officialTitle":285,"acronym":4,"eligibilityCriteria":286,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":287,"targetDuration":4,"studyType":21,"phases":289,"briefSummary":290,"conditions":291,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":319,"lastUpdatePostDateStruct":320,"startDateStruct":322,"completionDateStruct":324,"leadSponsor":326,"locationsCount":84},"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":288,"type":20},45,[128],"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.",[292,293,294,295,296,297,147,298,39,299,300,301,302,303,304,305,306,307,308,309,310,311,312,313,314,315,316,317,318],"Advanced Malignant Solid Neoplasm","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","Metastatic Colorectal 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 III Colorectal Cancer AJCC v8","Stage IIIA Colorectal Cancer AJCC v8","Stage IIIB Colorectal Cancer AJCC v8","Stage IIIC Colorectal Cancer AJCC v8","Stage IV 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":321,"type":47},"2026-05-04",{"date":323,"type":47},"2021-06-08",{"date":325,"type":20},"2029-04-01",{"name":327,"class":83},"Roswell Park Cancer Institute",{"id":329,"slug":330,"hasResults":11,"nctId":331,"briefTitle":332,"officialTitle":333,"acronym":4,"eligibilityCriteria":334,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":335,"targetDuration":4,"studyType":21,"phases":337,"briefSummary":339,"conditions":340,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":354,"lastUpdatePostDateStruct":355,"startDateStruct":357,"completionDateStruct":359,"leadSponsor":361,"locationsCount":84},"100442420","early-phase-1-pembrolizumab-and-lenvatinib-for-the-treatment-of-advanced-unresectable-or-metastatic-gastroesophageal-adenocarcinoma-100442420","NCT05041153","Pembrolizumab and Lenvatinib for the Treatment of Advanced, Unresectable, or Metastatic Gastroesophageal Adenocarcinoma","A Pilot Study of Pembrolizumab and Lenvatinib Combination Therapy in Patients With Previously Treated Advanced Gastroesophageal Adenocarcinoma","Inclusion Criteria:\n\n* The subject (or legally acceptable representative if applicable) provides written informed consent for the trial\n* Male and female subjects who are at least 18 years of age on day of signing informed consent with histologically and cytologically documented diagnosis as gastric or gastroesophageal adenocarcinoma\n* Has a documented, previously treated, advanced (unresectable and\u002For metastatic) gastroesophageal adenocarcinoma that is incurable and for which prior first-line or later-line standard of care (SOC) treatments have failed. Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line SOC treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence\n* Has submitted an evaluable tissue sample for biomarker analysis from a newly obtained irradiated. The tumor tissue submitted for analysis must be from a single tumor tissue specimen and of sufficient quantity and quality to allow biomarker study (see laboratory manual). A \"newly obtained\" tumor specimen, defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1, for biomarker characterization will be required for enrollment of all subjects. Tissue from tumor progressing at a site of prior radiation (at least 6 weeks interval after last radiation) may be allowed for biomarker characterization upon agreement from Merck. Subjects for whom newly-obtained samples cannot be provided (e.g., inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Merck\n* Has measurable disease based on RECIST 1.1 as assessed by the Investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale within 5 days of starting study treatment\n* Has a life expectancy of greater than 3 months per the judgment of the investigators\n* Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =\\\u003C 150\u002F90 mm Hg at screening and no change in antihypertensive medications within 1 week of cycle 1 day 1\n* Absolute neutrophil count (ANC) \\>= 1,500\u002FuL (specimens must be collected within 5 days prior to the start of study treatment)\n* Platelets \\>= 100,000\u002FuL (specimens must be collected within 5 days prior to the start of study treatment)\n* Hemoglobin \\>= 9 g\u002FdL or \\>= 5.6 mmol\u002FL without transfusion or EPO dependency (within 7 days of assessment) (specimens must be collected within 5 days prior to the start of study treatment)\n* Serum creatinine =\\\u003C 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) \\>= 60 mL\u002Fmin for subject with creatinine levels \\> 1.5 x institutional ULN (specimens must be collected within 5 days prior to the start of study treatment)\n\n  * Creatinine clearance should be calculated per institutional standard\n* Total bilirubin \\\u003C 1.5 x ULN OR direct bilirubin =\\\u003C ULN for subjects with total bilirubin levels \\> 1.5 x ULN (specimens must be collected within 5 days prior to the start of study treatment)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x ULN OR =\\\u003C 5 x ULN for subjects with liver metastases (specimens must be collected within 5 days prior to the start of study treatment)\n* Albumin \\>= 2.5 mg\u002FdL (specimens must be collected within 5 days prior to the start of study treatment)\n* International normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (specimens must be collected within 5 days prior to the start of study treatment)\n* Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of lenvatinib\n\n  * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR\n  * Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:\n\n    * Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a women of child birth potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.\n  * Please note that 30 days after lenvatinib is stopped, if the subject is on pembrolizumab only, no male contraception measures are needed\n* A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:\n\n  * Is not a WOCBP OR\n  * Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \\\u003C 1% per year) and has a low user dependency, or is abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 12.8 during the intervention period and for at least 120 days post pembrolizumab or 30 days post lenvatinib, whichever occurs last. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention\n  * A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention\n  * If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the subject must be excluded from participation if the serum pregnancy result is positive\n  * The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy\n\nExclusion Criteria:\n\n* Is currently participating in or has participated in a study of an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment.\n\n  * Note: Subjects who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent\n* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment\n* Has had major surgery within 3 weeks prior to first dose of study interventions.\n\n  * Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility\n* Has preexisting \\>= grade 3 gastrointestinal or non-gastrointestinal fistula\n* Has urine protein \\>= 1 g\u002F24 hours.\n\n  * Note: subjects with proteinuria \\>= 2+ (\\>= 100 mg\u002FdL) on urine dipstick testing\u002Furinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria\n* Has significant gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib\n* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.\n\n  * Note: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage\u002Fnecrosis following lenvatinib therapy\n* Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug\n* Significant cardiovascular impairment within 12 months of the first dose of study drug: such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability\n* Prolongation of corrected QT (QTc) interval to \\> 480 ms\n* Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multi-gated acquisition scan (MUGA) or echocardiogram (ECHO)\n* Has known intolerance or severe hypersensitivity (grade \\>= 3) to pembrolizumab, lenvatinib, or any of their excipients\n* Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2 agent, a VEGFR2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)\n* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 times the half-life time, whichever is shorter prior to allocation.\n\n  * Note: Subjects must have recovered from all adverse events (AEs) due to previously therapies to =\\\u003C grade 1 or baseline. Subjects with =\\\u003C grade 2 neuropathy may be eligible\n* Has received prior radiotherapy within 2 weeks prior to study day 1.\n\n  * Note: Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\\\u003C 2 weeks of radiotherapy) to non-central nervous system (CNS) disease\n* Has a known additional malignancy that is progressing or requires active treatment.\n\n  * Note: Subjects with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded\n* Has known active central nervous system (CNS) metastases and\u002For carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiological stable (i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to the first dose of trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability\n* Has an 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). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed\n* Has symptomatic ascites or pleural effusion. A subject who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible\n* Has a history of (non-infectious) pneumonitis that required treatment with steroids or has current pneumonitis\n* Has an active infection requiring systemic therapy\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator\n* Has known psychiatric or substance-abuse disorders that would interfere with cooperation with the requirements of the trial\n* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment\n* Has a known history of human immunodeficiency virus (HIV) (HIV 1\u002F2 antibodies).\n* Had an allogenic tissue\u002Fsolid organ or hematologic transplant\n* Has a known history of hepatitis B virus (HBV; hepatitis B surface antigen \\[HBsAg\\] reactive) or known active hepatitis C virus (HCV ribonucleic acid \\[RNA\\] \\[qualitative\\] is detected) infection.\n* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed",{"count":336,"type":20},15,[338],"EARLY_PHASE1","This early phase I trial studies the effect of pembrolizumab and lenvatinib in treating patients with gastroesophageal adenocarcinoma that has spread to other places in the body (advanced\u002Fmetastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and lenvatinib may kill more tumor cells.",[28,29,32,33,35,36,140,141,142,143,38,39,341,342,343,344,345,346,347,348,349,350,351,352,305,306,307,353,308,309,310,41,42],"Pathologic Stage III Gastric Cancer AJCC v8","Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IIIA Gastric Cancer AJCC v8","Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IIIB Gastric Cancer AJCC v8","Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IIIC Gastric Cancer AJCC v8","Pathologic Stage IV Gastric Cancer AJCC v8","Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage III Gastric Cancer AJCC v8","Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8","2026-01-09",{"date":356,"type":47},"2026-01-12",{"date":358,"type":47},"2022-02-14",{"date":360,"type":20},"2026-12-30",{"name":362,"class":83},"M.D. Anderson Cancer Center",{"id":364,"slug":365,"hasResults":11,"nctId":366,"briefTitle":367,"officialTitle":368,"acronym":4,"eligibilityCriteria":369,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":370,"targetDuration":4,"studyType":21,"phases":372,"briefSummary":373,"conditions":374,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":375,"lastUpdatePostDateStruct":376,"startDateStruct":378,"completionDateStruct":380,"leadSponsor":382,"locationsCount":84},"100489321","phase-2-propranolol-in-combination-with-pembrolizumab-and-standard-chemotherapy-for-the-treatment-of-unresectable-locally-advanced-or-metastatic-esophageal-or-gastroesophageal-junction-adenocarcinoma-100489321","NCT05651594","Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma","A Phase 2 Trial of Chemotherapy, Pembrolizumab, and Propranolol in Advanced Esophageal\u002FGastroesophageal Junction Adenocarcinoma Patients","Inclusion Criteria:\n\n* Age \\>= 18 years of age.\n* Participants must be newly diagnosed, treatment-naive with unresectable locally advanced or metastatic esophageal\u002Fgastroesophageal junction (GEJ) adenocarcinoma. Any prior systemic treatment for resectable disease must be six months or before. Prior PD-1\u002FPD-L1 treatment is allowed as long as the treatment was completed more than 1 year ago.\n* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1\n* Available archival Formalin-Fixed Paraffin-Embedded (FFPE) from a prior biopsy collected within 1 year or, participant must be willing to have a tissue biopsy taken prior to start of study treatment.\n* Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present.\n* Platelet \\>= 75,000\u002FuL\n* Hemoglobin \\>= 8 g\u002FdL (without transfusion in the past 14 days)\n* Absolute Neutrophil Count (ANC) \\>= 1500\u002FuL\n* Creatinine clearance (Cockcroft Gault) \\>= 30 mL\u002Fmin\n* Total bilirubin: =\\\u003C 2 × upper limit of normal (ULN) OR direct bilirubin =\\\u003C ULN for participants with total bilirubin levels \\> 2 × ULN\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase) (SGOT) and alanine transaminase (ALT) (serum glutamic-pyruvic transaminase) (SGPT) =\\\u003C 3 X institutional ULN (=\\\u003C 5 × ULN for participants with liver metastases)\n* Participants of child-bearing potential must have a negative pregnancy test at study entry and then 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* Ability to swallow and retain oral medication. If a patient is not able to swallow or is experiencing dysphagia that limits ability to swallow oral medication, they are still eligible for study provided they can swallow liquid formula propranolol or have an enteric feeding tube placed which will permit administration of crushed tablets or liquid formula propranolol. Liquid and tablet formulations may be used interchangeably for patients in the event of a shortage of either formulation\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* Patients with HER 2-positive cancer.\n* Patients with active, untreated central nervous system metastases or leptomeningeal disease.\n* Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation.\n\n  * Patients currently treated with systemic immunosuppressive agents: If a patient is currently on steroids, they must be on a steroid dose less than or equal to an equivalent prednisone dose of 10 mg daily.\n* Has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required treatment.\n* Has a concurrent Human Immunodeficiency Virus (HIV) infection.\n* Concurrent active Hepatitis B (defined as Hepatitis B virus surface antigen \\[HBsAg\\] positive and\u002For detectable Hepatitis B virus \\[HBV\\] deoxyribonucleic acid DNA) and Hepatitis C virus (defined as anti-HCV antibody \\[Ab\\] positive and detectable HCV ribonucleic acid \\[RNA\\]) infection. Note: Hepatitis B and C screening tests are not required unless known history of HBV and HCV infection.\n* Participants that are already on beta-adrenergic (B-AR) blockers for various indications.\n* Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\\\u003C2 weeks of radiotherapy) to non-central nervous system (CNS) disease.\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 or nursing female participants, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.\n* Other active cancers that require systemic treatment.\n* Contraindications to the use of beta-blockers, e.g.: uncontrolled depression, unstable angina pectoris, uncontrolled heart failure ( Grade III or IV), hypotension (systolic blood pressure \\\u003C100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), uncontrolled type I or type II diabetes mellitus (HbA1C \\> 8.5 or fasting plasma glucose \\> 160 mg\u002Fdl at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma etc.\n* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella\u002Fzoster etc.\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":371,"type":20},40,[23],"This phase II trial tests what effects the addition of propranolol to pembrolizumab and standard chemotherapy (mFOLFOX) may have on response to treatment in patients with esophageal or gastroesophageal junction cancer that cannot be removed by surgery and has spread to nearby tissue or lymph nodes (unresectable locally advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins). Cancer patients may be under a tremendous amount of stress with elevated levels of norepinephrine (a hormone produced by the adrenal glands in response to stress). Increased adrenergic stress may dampen the immune system, which beta-blockers, like propranolol, may be able to counteract. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in the standard chemotherapy regimen, mFOLFOX (leucovorin, fluorouracil and oxaliplatin) 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. Adding propranolol to pembrolizumab and standard mFOLFOX chemotherapy may increase the effectiveness of the pembrolizumab + mFOLFOX regimen.",[30,31,33,34,36,267,147,37,39,40,42],"2025-12-10",{"date":377,"type":47},"2025-12-16",{"date":379,"type":47},"2023-03-07",{"date":381,"type":20},"2029-03-30",{"name":327,"class":83},{"id":384,"slug":385,"hasResults":11,"nctId":386,"briefTitle":387,"officialTitle":388,"acronym":4,"eligibilityCriteria":389,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":390,"targetDuration":4,"studyType":21,"phases":392,"briefSummary":394,"conditions":395,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":424,"lastUpdatePostDateStruct":425,"startDateStruct":427,"completionDateStruct":429,"leadSponsor":431,"locationsCount":279},"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":391,"type":20},28,[393],"NA","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.",[396,397,398,399,400,401,402,403,404,405,406,407,408,409,410,245,39,166,411,412,413,348,414,415,416,417,351,418,353,308,419,420,309,421,422,310,423,315,194,316,198,317,202,318],"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 Colorectal Carcinoma","Metastatic Esophageal 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","Postneoadjuvant Therapy Stage IV Esophageal Squamous Cell Carcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Esophageal Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Esophageal Squamous Cell Carcinoma AJCC V8","Stage IV Anal Cancer AJCC v8","2025-09-30",{"date":426,"type":47},"2025-10-06",{"date":428,"type":47},"2020-08-07",{"date":430,"type":20},"2028-04-30",{"name":432,"class":83},"University of California, San Francisco",{"id":434,"slug":435,"hasResults":11,"nctId":436,"briefTitle":437,"officialTitle":438,"acronym":4,"eligibilityCriteria":439,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":63,"enrollmentInfo":440,"targetDuration":4,"studyType":21,"phases":442,"briefSummary":443,"conditions":444,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":445,"lastUpdatePostDateStruct":446,"startDateStruct":448,"completionDateStruct":450,"leadSponsor":452,"locationsCount":84},"100541446","phase-1-fruquintinib-in-combination-with-sintilimab-and-capeox-as-first-line-treatment-for-ggej-cancer-100541446","NCT06329973","Fruquintinib in Combination With Sintilimab and CAPEOX as First-line Treatment for G\u002FGEJ Cancer","A Single-arm, Open-label, Multicenter, Phase Ib\u002FII Study to Evaluate the Safety and Efficacy of Fruquintinib in Combination With Sintilimab and CAPEOX as 1L Treatment for Advanced Unresectable or Metastatic G\u002FGEJ Cancer (FUNCTION Research)","Inclusion Criteria:\n\n1. Subjects aged 18-75 years (including 18 and 75 years);\n2. Understand the research procedure and content, and voluntarily sign a written informed consent;\n3. Incurable advanced\u002Frecurrent gastric or gastroesophageal junction adenocarcinoma with histopathological and\u002For cytological confirmation of HER2-negative or HER2 status unknown;\n4. There is at least one measurable lesion according to RECIST 1.1 criteria;\n5. No previous treatment with VEGFR-targeting drugs or PD-1\u002FPD-L1 monoclonal antibody. Patients who had received platinum or paclitaxel or fluorouracil adjuvant chemotherapy after surgery and recurred more than 6 months after the end of chemotherapy without grade 2 toxicity or higher could be enrolled.\n6. Physical condition score (ECOG PS score) : 0-1 score;\n7. Expected survival ≥3 months;\n8. The main organs function well;That is, the relevant check indicators within 14 days before randomization meet the following requirements:\n\n   Hemoglobin ≥ 90 g\u002FL (no transfusion within 14 days); Neutrophil count \\> 1.5×109\u002FL; Platelet count ≥ 100×109\u002FL; Total bilirubin ≤ 1.5×ULN (upper limit of normal); Serum glutamic pyruvic aminotransferase (ALT) or serum glutamic oxalacetic aminotransferase (AST) ≤ 2.5×ULN; If there is liver metastasis, ALT or AST ≤ 5×ULN; Endogenous creatinine clearance ≥ 60 ml\u002Fmin (Cockcroft-Gault formula); Cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ 50%; Thyroid function index: thyroid stimulating hormone (TSH), free thyroxine (FT3\u002FFT4) in the normal range;\n9. Weight of more than 40 kg (including 40 kg), or BMI \\> 18.5\n10. Women who are fertile must have a negative urine or serum pregnancy test within 7 days prior to randomization and must consent to use highly effective contraception during the study period and for at least 120 days after the last administration of fruquintinib and sintilimab and for at least 180 days after the last administration of chemotherapy (Appendix 9);\n11. Men who are not sterilized must consent to use highly effective contraception during the study period and for at least 120 days after the last administration of fruquintinib and sintilimab and for at least 180 days after the last administration of chemotherapy (Appendix 9).\n\nExclusion Criteria:\n\n1. Patients with other malignant tumors in the past or at the same time, but have been cured of early tumors, including skin basal cell carcinoma, cervical carcinoma in situ, stage I lung cancer, stage I colorectal cancer and other tumors that researchers judge will not affect the patient's life in the short term can be excluded;\n2. Participated in other drug clinical trials within four weeks;\n3. have multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea, and intestinal obstruction);\n4. Have a history of bleeding, any bleeding event with a severity rating of CTCAE5.0 or higher occurring within 4 weeks prior to screening;\n5. Patients with known central nervous system metastasis or history of central nervous system metastasis before screening. For patients with clinically suspected CNS metastasis, CT or MRI examination must be performed within 28 days before enrollment to rule out CNS metastasis.\n6. Patients with hypertension who are not well controlled by single antihypertensive medication (systolic blood pressure \\> 140 mmHg, diastolic blood pressure \\> 90mmHg); Patients with history of unstable angina pectoris; Patients with newly diagnosed angina pectoris or myocardial infarction within 3 months prior to screening; Arrhythmias (including QTcF: ≥450 ms in men and ≥470 ms in women) requiring long-term use of antiarrhythmic drugs and New York Heart Association grade ≥II cardiac insufficiency;\n7. long-term unhealed wounds or incomplete healing fractures;\n8. Imaging shows that the tumor has invaded important blood vessels, or the investigator determines that the patient's tumor is highly likely to invade important blood vessels during treatment and cause fatal massive bleeding;\n9. Patients with abnormal coagulation function and bleeding tendency (14 days before randomization must meet: INR in the normal range without the use of anticoagulants, or no clinically significant abnormalities); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogs; Low doses of warfarin (1 mg orally, once daily) or low doses of aspirin (up to 100 mg daily) are permitted for prophylactic purposes if INR ≤ 1.5;\n10. Occurrence of arteriovenous thrombosis events within 6 months prior to screening, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis (except venous thrombosis caused by intravenous catheterization in previous chemotherapy and cured by investigators), pulmonary embolism, etc.;\n11. Urine routine indicated urinary protein ≥++ and confirmed 24-hour urinary protein quantity \\> 1.0g;\n12. Have used immunotargeted therapy drugs;\n13. Have a history of immunodeficiency, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation;\n14. Patients with infectious pneumonia, non-infectious pneumonia, interstitial pneumonia and other patients requiring corticosteroids;\n15. A history of serious chronic autoimmune diseases, such as systemic lupus erythematosus; History of ulcerative enteritis, Crohn's disease and other inflammatory bowel diseases, irritable bowel syndrome and other chronic diarrheal diseases; A history of sarcoidosis or tuberculosis; History of active hepatitis B, hepatitis C and HIV infection; Well controlled non-severe immune diseases such as dermatitis, arthritis, psoriasis, etc. can be included. Hepatitis B virus drops \\\u003C1000copy\u002Fml could be included in the group.\n16. Patients with hypersensitivity to human or murine monoclonal antibodies;\n17. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;\n18. pleural effusion or abdominal effusion with clinical symptoms requiring clinical intervention;\n19. Patients who do not follow medical advice, do not use drugs according to regulations, or have incomplete data that can affect the evaluation of efficacy or safety;\n20. In the judgment of the investigator, there is a serious concomitant disease that endangers the patient's safety or interferes with the patient's completion of the study.",{"count":441,"type":20},70,[128,23],"Based on the current status and progress in the treatment of gastric cancer, our center prospectively designed a first-line comprehensive treatment plan for unresectable or postoperative recurrent advanced gastric\u002Fgastroesophageal conjoint adenocarcinoma, fruquintinib + sintilimab + oxaliplatin + Capecitabine (CAPEOX), which utilizes the tumor immunomodulation and vascular normalization effects of fruquintinib. While improving the effective perfusion of intravenous chemotherapy with CAPEOX regimen, further combining with PD-1 monoclonal antibody to regulate the immunosuppressive microenvironment and reactivate the anti-tumor immune response of the body. An exploratory dose-climbing trial was designed to evaluate the clinical efficacy and safety of fruquintinib in combination with Sintilimab and CAPEOX in clinical practice. At the same time, changes in genome, pathology and immune microenvironment of tumor-related tissues before and after treatment were observed, and molecular markers related to curative effect were screened to explore the molecular mechanism affecting the curative effect of combination therapy, and further enrichment of therapeutic advantage groups to improve the surgical conversion rate laid the foundation for future large-scale clinical studies",[39],"2025-07-14",{"date":447,"type":47},"2025-07-17",{"date":449,"type":47},"2024-02-28",{"date":451,"type":20},"2028-06-28",{"name":453,"class":454},"Henan Cancer Hospital","OTHER_GOV",{"id":456,"slug":4,"hasResults":11,"nctId":59,"briefTitle":60,"officialTitle":61,"acronym":4,"eligibilityCriteria":62,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":63,"enrollmentInfo":457,"targetDuration":4,"studyType":21,"phases":458,"briefSummary":67,"conditions":459,"keywords":460,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":461,"lastUpdatePostDateStruct":462,"startDateStruct":464,"completionDateStruct":465,"leadSponsor":467,"locationsCount":84},"100426996",{"count":65,"type":20},[23],[38,39,69],[71,72,73,74],"2024-03-14",{"date":463,"type":47},"2024-03-18",{"date":78,"type":47},{"date":466,"type":20},"2027-06-30",{"name":82,"class":83},{"id":469,"slug":470,"hasResults":11,"nctId":471,"briefTitle":472,"officialTitle":473,"acronym":4,"eligibilityCriteria":474,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":475,"targetDuration":4,"studyType":21,"phases":477,"briefSummary":478,"conditions":479,"keywords":4,"overallStatus":43,"whyStopped":4,"lastUpdateSubmitDate":502,"lastUpdatePostDateStruct":503,"startDateStruct":505,"completionDateStruct":506,"leadSponsor":508,"locationsCount":84},"100495576","phase-2-cpi-613-devimistat-in-combination-with-hydroxychloroquine-and-5-fluorouracil-or-gemcitabine-in-treating-patients-with-advanced-chemorefractory-solid-tumors-100495576","NCT05733000","CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors","Phase II Open-Label Multi-Cohort Study Evaluating CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Patients With Advanced Chemorefractory Colorectal, Pancreatic, or Other Solid Cancers","Inclusion Criteria:\n\n* Patients must have histologically confirmed cancer for which standard-of-care curative measures are no longer effective or be intolerant to those agents. Patients in cohort 1 must have colorectal cancer. Patients in cohort 2 must have pancreatic cancer. Patients in cohort 3 may have any of the following cancers:\n\n  * Biliary\n  * Gastroesophageal\n  * Urothelial\n  * Ovarian\n  * Non-small cell lung (adenocarcinoma only)\n* Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 disease.\n* Patients must have radiographic documentation of metastatic disease with imaging within =\\\u003C 6 weeks prior to registration.\n* Patients must be age \\>= 18 years.\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Performance Status of 2 will be allowed with approval from principle investigator (PI) on a case-by case basis.\n\n  * Note: Performance status of 2 will be allowed with approval from PI on a case-by case basis. Documentation of PI approval in these cases will be stored with inclusion\u002Fexclusion signed checklist for patient and\u002For in patient's shadow chart.\n* Patients must have exhausted all available molecularly targeted therapies (e.g., anti-PD-1\u002Fanti-PD-L1 agents where indicated).\n* Absolute neutrophil count (ANC) \\>= 1,500\u002FmcL (within the last 14 days of screening)\n* Hemoglobin (Hgb) \\>= 9 g\u002FdL (within the last 14 days of screening) (Transfusions permitted. Eligibility labs should be drawn \\>= 7 days from transfusion).\n* Platelets (PLT) \\>= 100,000\u002FmcL (within the last 14 days of screening) (Transfusions permitted. Eligibility labs should be drawn \\>= 7 days from transfusion).\n* INR (international normalized ratio) =\\\u003C 1.6 (within the last 14 days of screening) (unless receiving anticoagulation therapy) If receiving anticoagulant: INR =\\\u003C 3.0 and no active bleeding, (i.e., no bleeding within 14 days prior to first dose of study therapy).\n* Total bilirubin =\\\u003C1.5 x Institutional upper limit of normal (ULN) (within the last 14 days of screening)\n\n  * Note: Patients with Gilbert's Syndrome are exempt. Patients with liver metastases with no significant bilirubin obstruction may have a total bilirubin level of =\\\u003C 2.0 mg\u002FdL.\n* Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) =\\\u003C 2.5 x institutional ULN (within the last 14 days of screening)\n\n  * Note: If liver metastases are present, then =\\\u003C 5 x ULN is allowed.\n* Alanine transaminase (ALT) serum glutamic-pyruvic transaminase (SGPT) =\\\u003C 2.5 x institutional ULN (within the last 14 days of screening)\n\n  * Note: If liver metastases are present, then =\\\u003C 5 x ULN is allowed.\n* Serum albumin \\> 3.0 g\u002FdL (within the last 14 days of screening)\n* Creatinine =\\\u003C 1.5 x ULN OR glomerular filtration rate (GFR) \\>= 50 mL\u002Fmin\u002F1.73 m\\^2 (within the last 14 days of screening)\n\n  * eGFR is estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation\n* The effects of combination treatment of CPI-613, 5-FU, gemcitabine, and HCQ on the developing human fetus are unknown. For this reason and because antineoplastic agents as well as other therapeutic agents used in this trial are known to be teratogenic, patients of child-bearing potential (POCBP) regardless of gender must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 180 days following completion of therapy. Patients who can impregnate their partners regardless of gender must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation, and for 180 days following completion of therapy. Should a patient become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform their treating physician immediately.\n\n  * Note: At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, postovulation methods\\] and withdrawal are not acceptable methods of contraception.)\n  * Note: A POCBP is any person with an egg-producing reproductive tract (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:\n\n    * Has not undergone a hysterectomy or bilateral oophorectomy\n    * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months)\n* POCBP must have a negative pregnancy test prior to registration on study.\n\n  * Note: If negative pregnancy test result is \\>7 days from first dose of study treatment it must be repeated at time of first dose of study treatment (with any of the four drugs used in this study).\n* For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration.\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. Patients with HCV infection who are currently on treatment, must have an undetectable HCV viral load. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardio toxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Patients must be class 2B or better.\n\n  * Note: Patients with pacemakers where corrected QT interval (QTc) is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study.\n* Patients must have the ability to understand and the willingness to sign a written informed consent document for the duration of the entirety of the study.\n* Patients must be reliable, willing to make themselves available for the duration of the entire study and willing to follow screening procedures.\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).\n\n  * Note: Patients who experience adverse events of alopecia and peripheral neuropathy that have not recovered are eligible; patients with any lab abnormality that is above grade 1 related to previous therapy found to be not clinically significant will also be eligible.\n* Patients with symptomatic brain metastases currently using corticosteroids.\n\n  * Note: Patients with brain metastases who are asymptomatic and off corticosteroids for at least one week are eligible.\n* Patients with severe obstructive pulmonary disease or interstitial lung disease.\n* Patients with a history of myocardial infarction that is \\\u003C90 days prior to registration.\n* Patients using concomitant medications that prolong the QT\u002FQTc intervals. For example, patients receiving amiodarone. Using amiodarone together with hydroxychloroquine can increase the risk of long QT syndrome that although rare, may be serious, and potentially life-threatening.\n* Patients with a history of additional risk factors for drug-induced QT prolongation or Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome).\n* Patients with major surgery or significant traumatic injury =\\\u003C 21 days prior to registration.\n* Patients receiving treatment with low dose chemotherapy concurrent with radiation =\\\u003C 21 days prior to registration.\n\nOR patients who have had chemotherapy or radiotherapy =\\\u003C 21 days (42 days for nitrosoureas or mitomycin C) prior to registration.\n\n* Note: Palliative radiation before and during study participation is permissible providing it is not to a target lesion.\n\n  * Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:\n* Ongoing or active infection requiring systemic treatment.\n* Clinically significant complications such as perforation, gastrointestinal bleeding, or diverticulitis within 42 days prior to registration.\n* Symptomatic congestive heart failure; symptomatic coronary artery disease, symptomatic angina pectoris, or symptomatic myocardial infarction.\n* Unstable angina pectoris.\n* Unstable cardiac arrhythmia.\n* Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Active substance abuse.\n* Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints.\n\n  * Patients who are pregnant or nursing.\n  * Patients with Fridericia-corrected QT interval (QTcF) \\> 470 msec (female) or \\> 450 (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG) abnormality that in the opinion of the investigator would preclude safe participation in the study.\n  * Patients who have pre-existing retinopathy of the eye.\n  * Patients who are unable to swallow or retain and absorb oral medication\n  * Patients with known hypersensitivity to any of the following: CPI or its inactive components, 4-aminoquinoline compounds, or quinine.\n  * Patients with poorly controlled diabetes mellitus (glycosylated hemoglobin (HbA1c) of \\> 7%, pre-prandial capillary plasma glucose \\> 130mg\u002Fdl, and peak postprandial capillary plasma glucose of \\> 180mg\u002Fdl).",{"count":476,"type":20},94,[23],"This phase II trial tests how well CPI-613 (devimistat) in combination with hydroxychloroquine (HCQ) and 5-fluorouracil (5-FU) or gemcitabine works in patients with solid tumors that may have spread from where they first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that have not responded to chemotherapy medications (chemorefractory). Metabolism is how the cells in the body use molecules (carbohydrates, fats, and proteins) from food to get the energy they need to grow, reproduce and stay healthy. Tumor cells, however, do this process differently as they use more molecules (glucose, a type of carbohydrate) to make the energy they need to grow and spread. CPI-613 works by blocking the creation of the energy that tumor cells need to survive, grow in the body and make more tumor cells. When the energy production they need is blocked, the tumor cells can no longer survive. Hydroxychloroquine is a drug used to treat malaria and rheumatoid arthritis and may also improve the immune system in a way that tumors may be better controlled. Fluorouracil is in a class of medications called antimetabolites. It works by killing fast-growing abnormal cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. CPI-613 (devimistat) in combination with hydroxychloroquine and 5-fluorouracil or gemcitabine may work to better treat advanced solid tumors.",[480,481,29,482,292,483,484,485,33,36,486,409,39,487,488,489,174,490,491,492,493,494,495,496,497,311,178,498,499,315,195,500,501],"Advanced Biliary Tract Carcinoma","Advanced Colorectal Carcinoma","Advanced Lung Adenocarcinoma","Advanced Ovarian Carcinoma","Advanced Pancreatic Carcinoma","Advanced Urothelial Carcinoma","Metastatic Biliary Tract Carcinoma","Metastatic Lung Adenocarcinoma","Metastatic Ovarian Carcinoma","Metastatic Pancreatic Carcinoma","Refractory Biliary Tract Carcinoma","Refractory Colorectal Carcinoma","Refractory Gastroesophageal Junction Adenocarcinoma","Refractory Lung Adenocarcinoma","Refractory Ovarian Carcinoma","Refractory Pancreatic Carcinoma","Refractory Urothelial Carcinoma","Stage II Pancreatic Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","2023-03-08",{"date":504,"type":47},"2023-03-10",{"date":502,"type":47},{"date":507,"type":20},"2030-03-04",{"name":278,"class":83}]