[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-biliary-tract-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-biliary-tract-carcinoma":33},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,60,90,112,141],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":48,"lastUpdatePostDateStruct":49,"startDateStruct":52,"completionDateStruct":54,"leadSponsor":56,"locationsCount":59},"100624088","phase-4-morning-versus-afternoon-administration-of-immunotherapy-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-knight-shift-study-100624088",false,"NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases","ALL","18 Years",{"count":19,"type":20},160,"ESTIMATED","INTERVENTIONAL",[23],"PHASE4","This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.",[26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Hepatocellular Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Metastatic Head and Neck Squamous Cell Carcinoma","Metastatic Hepatocellular Carcinoma","Metastatic Lung Non-Small Cell Carcinoma","Metastatic Malignant Solid Neoplasm","Metastatic Melanoma","Metastatic Renal Cell Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","Stage III Hepatocellular Carcinoma AJCC v8","Stage III Lung Cancer AJCC v8","Stage III Renal Cell Cancer AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","Stage IV Lung Cancer AJCC v8","Stage IV Renal Cell Cancer AJCC v8","RECRUITING","2026-06-10",{"date":50,"type":51},"2026-06-12","ACTUAL",{"date":53,"type":51},"2026-06-08",{"date":55,"type":20},"2028-12-31",{"name":57,"class":58},"OHSU Knight Cancer Institute","OTHER",1,{"id":61,"slug":62,"hasResults":11,"nctId":63,"briefTitle":64,"officialTitle":65,"acronym":4,"eligibilityCriteria":66,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":67,"targetDuration":4,"studyType":21,"phases":69,"briefSummary":72,"conditions":73,"keywords":4,"overallStatus":80,"whyStopped":4,"lastUpdateSubmitDate":81,"lastUpdatePostDateStruct":82,"startDateStruct":84,"completionDateStruct":86,"leadSponsor":88,"locationsCount":59},"100638129","phase-1-bms-986504-in-combination-with-pemetrexed-for-the-treatment-of-metastatic-solid-tumors-with-mtap-deletion-100638129","NCT07594626","BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion","A Phase Ib\u002FII Basket Study of BMS-986504 in Combination With Pemetrexed for Metastatic Solid Tumors With MTAP Deletion","Inclusion Criteria:\n\n* COHORT A (INCLUDING SAFETY RUN IN, STAGE I AND STAGE II) AND COHORT B:\n* Patients must have pathologically or cytologically confirmed metastatic solid tumor of gastrointestinal origin with MTAP deletion including pancreatic cancer, biliary cancer, esophageal cancer and colon cancer (Cohort A) or other metastatic solid malignancy with MTAP deletion (Cohort B) confirmed by validated next generation sequencing tissue techniques only\n\n  * NOTE: Both internal and external validated next generation sequencing (NGS) panels are acceptable\n* Progressive disease (PD) after one previous standard of care line of treatment\n\n  * NOTE: symptoms from clinical evaluation for PD will be sufficient\n* Patients must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, measured preferably by computed tomography (CT) scan\n\n  * Note: Tumor lesions in a previously irradiated area are not considered measurable unless they show unequivocal progression\n  * NOTE: There is no limit on previous treatment lines\n* Patients who have received any neoadjuvant or systemic chemotherapy are eligible\n\n  * Note: treatment cannot have included prior pemetrexed unless in the case of non-small cell lung cancer (NSCLC) cancer type. Any prior intravesical therapy, or immunotherapy is allowed. At least 3 weeks (21 days) wash-out period from treatment since prior chemotherapy or radiation therapy or targeted agent is required\n* Patients must be aged ≥ 18 years\n* Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1\n* Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL (growth factor allowed and can be added at the discretion of the treating oncologist\n\n  * Growth factors are excluded from being used during the DLT observation period (cycle 1) unless they are being used to treat a grade 4 adverse event which will be counted as a DLT. If growth factors are being used for grade ≤ 3 toxicity, then patients will not be evaluable for DLT assessment\n* Hemoglobin (Hgb) ≥ 8.5 g\u002FdL (without the need for transfusion within the previous one week)\n* Platelets (PLT) ≥ 100,000\u002FmL (without the need for platelet transfusion within the previous one week)\n* Total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN), except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin ≤ 3.0 mg\u002FdL\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present\n* Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional ULN or ≤ 5 x ULN if documented liver metastases are present\n* Creatinine clearance ≥ 60 mL\u002Fmin\u002F1.73 m\\^2 using the standard Cockcroft and Gault formula\n* Patients must have the ability to comply with folic acid, vitamin B12 and steroids as directed by study team and as per standard of care for pemetrexed use\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Pemetrexed is known to be teratogenic. Reproductive toxicology studies with MRTX1719 have not been performed. The investigator or designee shall counsel patients of childbearing potential (POCBP) participants and male (as assigned at birth) participants who are sexually active with POCBP on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of study intervention present in seminal fluid to a developing fetus, even if the participant has undergone a successful vasectomy or if the partner is pregnant. If needed, participants should be advised to seek advice about egg or sperm donation and cryopreservation of germ cells before treatment\n\n  * Patients of childbearing potential POCBP\n\n    * A POCBP is any patient with an egg-producing reproductive tract who meets the following criteria:\n\n      * Has not undergone a hysterectomy or bilateral oophorectomy\n      * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months)\n    * POCBP are not permitted to use hormonal contraceptive methods alone as a highly effective method of contraception and must use an additional non-hormonal highly effective method of contraception. POCBP must agree to use a combination of a hormonal and a non-hormonal contraceptive method or a non-hormonal method alone that is highly effective (with a failure rate of \\\u003C 1% per year) during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer\n    * POCBP participants must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction for the same period\n    * Male (as assigned at birth) participants will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with POCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant or breastfeeding. Male (as assigned at birth) participants should continue to use a condom during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer\n    * POCBP partners of male (as assigned at birth) participants should be advised to use a highly effective method of contraception during the intervention period and for at least 6 months after the last dose of study intervention for the male participant, or according to approved local product label requirements for pemetrexed, whichever is longer\n    * Male (as assigned at birth) participants with a pregnant or breastfeeding partner must agree to remain abstinent from sexual activity or use a male condom during any sexual activity (eg, vaginal, anal, oral), even if the participant has undergone a successful vasectomy, during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer\n    * Male (as assigned at birth) participants must refrain from donating sperm during the intervention period and for at least 6 months after the last dose of study intervention, or according to approved local product label requirements for pemetrexed, whichever is longer\n    * Breastfeeding partners of male (as assigned at birth) participants should be advised to consult their health care provider about using appropriate highly effective contraception during the time the male participant is required to use condoms\n    * POCBP must have a negative pregnancy test prior to registration on study\n* The ability to interrupt nonsteroidal antiinflammatory drugs (NSAIDS) or aspirin at higher dose (\\> 1.3 g daily) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed\n\nExclusion Criteria:\n\n* STAGE I AND II, COHORT A (INCLUDING SAFETY RUN IN) AND B:\n* Patients who received prior pemetrexed containing chemotherapy (apart from NSCLC)\n* Patients with prior treatment with a PRMT5 or MAT2A inhibitor therapy\n* Patients with pre-existing clinically significant interstitial lung disease (ILD)\n* Patients who have had chemotherapy or radiotherapy ≤ 21 days prior to planned treatment start date.\n\n  * Note: seven days or fewer of palliative radiotherapy for non-CNS disease, is permitted. No wash-out is required\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia and neuropathy per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0\n* Patients who are receiving any other investigational agents or devices. Patients start of study treatment will be based on their discontinuation and recovery from clinically significant adverse events from their most recent therapy or intervention prior to study enrollment\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pemetrexed\n* Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:\n\n  * Ongoing or active infection requiring systemic treatment\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints\n* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification\n\n  * Note: To be eligible for this trial, patients should be class 2B or better\n* Patients with presence of third space fluid which cannot be controlled by drainage\n\n  * Note: For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy\n* Patients who are not able to understand and voluntarily sign a written informed consent and is not willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures\n* Patients who are pregnant or nursing\n* Patients with history of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications\n* Patients with Fridericia's formula-corrected QT interval (QTcF) prolongation \\> 480 msec, except for right bundle branch block, per the investigator's assessment\n* Patients with ongoing need for a medication with a known risk of Torsade's de Pointes that cannot be switched to an alternative treatment prior to study entry\n* Patients with ongoing need for a medication known as a strong inhibitor or strong inducer of cytochrome P450 3A4 (CYP3A4) and\u002For P-glycoprotein (P-gp) or a proton-pump inhibitor and potassium-competitive acid blockers that cannot be switched to an alternative treatment prior to study entry\n\n  * NOTE: The following drug interaction databases and other literature can be utilized to determine the CYP3A4\u002FP-gp inhibitors and inducers\n  * Note: Please consult with the manufacturer for any uncertainties regarding potential CYP3A4 and P-gp modulators\n* Patients with inability to comply with restrictions and prohibited treatments\n* Patients taking any botanical preparation (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study within 4 weeks prior to treatment. The concurrent use of any botanical preparation is not permitted while on study\n* Patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration. Please note this lab is not a requirement for eligibility, however, if it 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 chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Please note this lab is not a requirement for eligibility; however if 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, they are eligible if they have an undetectable HCV viral load. 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 who take live\u002Fattenuated vaccine received within 30 days of first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction\n* Patient has not received the final dose of any of the following treatments\u002F procedures with the specified minimum intervals before first dose of study drug:\n\n  * Surgery with general anesthesia - within 7 days of first dose of study drug\n  * Surgery with local anesthesia - with 3 days of first dose of study drug",{"count":68,"type":20},72,[70,71],"PHASE1","PHASE2","This phase Ib\u002FII trial tests the safety and side effects of BMS-986504 in combination with pemetrexed and how well the combination works in treating patients with solid tumors with MTAP deletion and that has spread from where it first started (primary site) to other places in the body (metastatic). The MTAP gene helps cells recycle important parts needed to make deoxyribonucleic acid (DNA), which is needed for cell growth and function. MTAP deletion means that the MTAP gene is missing. BMS-986504, a PRMT5 inhibitor, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Giving BMS-986504 in combination with pemetrexed may be safe, tolerable, and\u002For effective in treating patients with metastatic solid tumors with MTAP deletion.",[33,74,75,76,37,77,78,79],"Metastatic Colon Carcinoma","Metastatic Esophageal Carcinoma","Metastatic Malignant Digestive System Neoplasm","Metastatic Pancreatic Carcinoma","Stage IV Colon Cancer AJCC v8","Stage IV Pancreatic Cancer AJCC v8","NOT_YET_RECRUITING","2026-05-13",{"date":83,"type":51},"2026-05-19",{"date":85,"type":20},"2027-12-09",{"date":87,"type":20},"2030-12-09",{"name":89,"class":58},"Northwestern University",{"id":91,"slug":92,"hasResults":11,"nctId":93,"briefTitle":94,"officialTitle":95,"acronym":4,"eligibilityCriteria":96,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":97,"targetDuration":4,"studyType":21,"phases":99,"briefSummary":100,"conditions":101,"keywords":4,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":103,"lastUpdatePostDateStruct":104,"startDateStruct":106,"completionDateStruct":108,"leadSponsor":110,"locationsCount":59},"100601227","phase-1-emavusertib-ca-4948-in-combination-with-cisplatin-gemcitabine-and-durvalumab-in-patients-with-untreated-advanced-or-metastatic-biliary-tract-cancer-100601227","NCT07107750","Emavusertib (CA-4948) in Combination With Cisplatin, Gemcitabine, and Durvalumab in Patients With Untreated Advanced or Metastatic Biliary Tract Cancer","Phase I Trial of Emavusertib (CA-4948) in Combination With Cisplatin, Gemcitabine, and Durvalumab in Patients With Untreated Advanced or Metastatic Biliary Tract Cancer","Inclusion Criteria:\n\n* Advanced unresectable or metastatic histologically or cytologically confirmed adenocarcinoma of the biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma. Patients whose tumor have mixed histology but predominantly (\\>50%) adenocarcinoma are allowed.\n* Measurable defined by RECIST v1.1.\n* No prior systemic treatment for advanced unresectable or metastatic BTC with the following exceptions:\n\n  * Neoadjuvant or adjuvant systemic therapy completed \\> 6 months from planned C1D1.\n  * Up to two prior cycles of gemcitabine\u002Fcisplatin\u002Fanti-PD1 with no evidence of disease progression is allowed\n* At least 18 years of age.\n* ECOG performance status 0, 1, or 2\n* Adequate bone marrow and organ function as defined below:\n\n  * Absolute neutrophil count ≥ 1.5 K\u002Fcumm\n  * Platelets ≥ 100 K\u002Fcumm\n  * Hemoglobin ≥ 9.0 g\u002FdL\n  * Total bilirubin ≤ 1.5 x IULN or ≤ 3 x IULN in patients with documented Gilbert's syndrome\n  * AST(SGOT)\u002FALT(SGPT) ≤ 2 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN\n  * Creatinine clearance ≥ 35 mL\u002Fmin by Cockcroft-Gault\n  * INR ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤1.5 x IULN\n* Creatinine phosphokinase (CPK) elevation at screening \\\u003C Grade 2 (CPK \\\u003C 2.5 x IULN).\n* Patients on a cholesterol lowering statin must be on a stable dose with no dose changes within 3 weeks prior to study start.\n* The effects of emavusertib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 90 days after completion of the study.\n* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.\n\nExclusion Criteria:\n\n* Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment. Use of medical marijuana is permitted.\n* A history of other malignancy with the exception of 1) malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease; 2) or known indolent malignancies that do not require treatment and will likely not alter the course of treatment of BTC in the opinion of the investigator\n* History of allogeneic organ or stem cell transplant.\n* Currently receiving any other investigational therapeutic agents. Investigational tracers related to imaging studies are allowed with a 7 day-washout.\n* Clinically active CNS metastasis; treated and asymptomatic metastasis allowed at the discretion of the sponsor\u002Finvestigator or site PI. Radiotherapy to the brain must be completed \\> 10 days prior to planned C1D1.\n* Chemoradiation with curative intent within 6 months prior to C1D1 of study therapy.\n* Palliative radiation therapy within 10 days prior to C1D1 of study therapy.\n* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to emavusertib, gemcitabine, cisplatin, durvalumab, or other agents used in the study.\n* Concomitant use of drugs with a known risk of causing prolonged QTc (with exception of Zofran if needed for supportive care) and\u002For Torsades de Pointes or a history of risk factors for Torsades de Pointes.\n* Presence of interstitial lung disease or pneumonitis ≥ G2 at time of screening.\n* Administration of a live attenuated vaccine within 30 days prior to C1D1\n* QTc (Fridericia) \\>470ms on screening EKG.\n* Gastrointestinal condition which could impair absorption of emavusertib or inability to ingest emavusertib in the opinion of the investigator.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia in the opinion of the investigator.\n* Pregnant and\u002For breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of C1D1.\n* Patients with known HIV are eligible unless their CD4+ T-cell counts are \\\u003C 350 cells\u002FmcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines and in line with contraindicated concomitant medications is recommended.\n* Participants with active, known, or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll after discussion with the sponsor-investigator or site PI.\n* Participants with a condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study treatment except for adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: treatment with a short course of steroids (\\\u003C 5 days) up to 7 days prior to initiating study treatment is permitted. Inhaled intranasal, intra-articular, and topical steroid uses are permitted.\n* History of grade 3 or greater rhabdomyolysis that did not completely resolve.\n* Patients are unwilling to adhere to the lifestyle guidance",{"count":98,"type":20},48,[70],"Based on preclinical data from the Lim lab (WUSM), the investigators hypothesize that IRAK4 inhibition cripples tumor-intrinsic survival signaling and effectively overcomes the desmoplastic and immune-suppressive tumor microenvironment (TME) to render chemo- and immunotherapies effective in GI malignancy. Therefore, this trial is designed to evaluate the combination of emavusertib (CA-4948) and standard chemoimmunotherapy in untreated advanced or metastatic biliary tract cancer (BTC).",[102,33],"Metastatic Biliary Tract Cancer","2026-03-30",{"date":105,"type":51},"2026-04-03",{"date":107,"type":51},"2026-03-27",{"date":109,"type":20},"2032-05-31",{"name":111,"class":58},"Washington University School of Medicine",{"id":113,"slug":114,"hasResults":11,"nctId":115,"briefTitle":116,"officialTitle":117,"acronym":118,"eligibilityCriteria":119,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":120,"enrollmentInfo":121,"targetDuration":4,"studyType":21,"phases":123,"briefSummary":125,"conditions":126,"keywords":4,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":131,"lastUpdatePostDateStruct":132,"startDateStruct":134,"completionDateStruct":136,"leadSponsor":138,"locationsCount":140},"100597728","phase-3-trastuzumab-plus-chemotherapy-vs-chemotherapy-alone-in-first-line-her2-positive-advanced-biliary-tract-cancer-patients-100597728","NCT07062263","Trastuzumab Plus Chemotherapy vs Chemotherapy Alone in First-line HER2 Positive Advanced Biliary Tract Cancer Patients","Trastuzumab Plus Chemotherapy vs Chemotherapy Alone in First-line HER2 Positive Advanced Biliary Tract Cancer Patients - a Randomized Non-blinded Two-arm Phase III Prospective Clinical Trial (TAB-2 Study).","TAB-2","Inclusion Criteria:\n\nHistologically confirmed adenocarcinoma of the biliary tract, with the following specifications -\n\n1. Biliary tract cancers include gallbladder cancer, intrahepatic cholangiocarcinoma, and perihilar cholangiocarcinoma.\n2. HER2-positive by IHC or FISH\n3. Age \\>=18 years.\n4. ECOG performance status 0 - 2.\n5. Unresectable or metastatic cancer.\n6. Patient does not have any contraindications to receive chemotherapy or trastuzumab.\n7. Adequate hematological, hepatic, and renal function parameters- Hematological- Hb\\> 80 g\u002FL, ANC ≥ 1.5 x 109\u002FL, platelets ≥ 100 x 109\u002FL. Liver functions- bilirubin ≤ 2 x upper limit normal (ULN), AST\u002FALT ≤ 5 x ULN, alkaline phosphatase ≤ 6 x upper limit normal (ULN) S. albumin ≥ 30 g\u002FL.\n\n   Renal function- Creatinine ≤ 1.5 ULN, Creatinine clearance \\>= 30 mL\u002Fmin.\n8. Normal cardiac ejection fraction and cardiac function, as assessed by echocardiography, ejection fraction (EF) \\>=50% or above the lower limit of normal. ECG with no clinically relevant abnormalities.\n9. Women of childbearing age should have a negative pregnancy test at the time of randomization and should be willing to use adequate contraception during the treatment phase of the trial.\n10. Subjects must provide written informed consent prior to the performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up assessments and procedures.\n11. Subjects who have received adjuvant chemotherapy will be considered eligible provided that therapy is completed more than 12 months before study enrollment. Patients who have received radiation therapy and surgery will also be eligible provided the interventions have been completed 3 and 2 weeks, respectively, before enrolment in the study.\n12. Negative serum pregnancy test (if applicable) and willing for adequate contraception.\n13. At least one measurable disease according to RECIST criteria.\n14. Life expectancy of at least 12 weeks.\n\nExclusion Criteria:\n\n1. Distal cholangiocarcinoma\n2. Known hypersensitivity or contraindications against gemcitabine, cisplatin, Nab- paclitaxel, or trastuzumab.\n3. Clinically significant active coronary heart disease, cardiomyopathy, or congestive heart failure, NYHA III-IV.\n4. Clinically significant valvular defect.\n5. Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix.\n6. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.\n7. Baseline neuropathy \\> NCI Grade I.\n8. Subject pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment.\n9. Received prior chemotherapy within 1 year.\n10. Any active ILD\u002F history of lung illness requiring bronchodilator drugs.\n11. Patients with prior chemotherapy for metastatic disease will be ineligible for enrollment in the study.","99 Years",{"count":122,"type":20},220,[124],"PHASE3","This is a randomized, open-label, two-arm, Phase III clinical trial evaluating the efficacy and safety of trastuzumab plus chemotherapy versus chemotherapy alone as first-line treatment in patients with HER2-positive advanced or metastatic biliary tract cancers (BTC). HER2-positive BTCs represent a molecular subset of these rare cancers, associated with poor prognosis and limited treatment options.\n\nEligible patients with histologically confirmed HER2-positive (IHC 3+ or IHC 2+ with FISH amplification) unresectable or metastatic biliary tract adenocarcinoma-including gallbladder cancer, intrahepatic, and perihilar cholangiocarcinoma-will be randomized in a 1:1 ratio. Participants in the intervention arm (Arm A) will receive either gemcitabine and cisplatin with or without nab-paclitaxel plus trastuzumab, while those in the control arm (Arm B) will receive chemotherapy alone (gemcitabine + cisplatin with or without nab-paclitaxel). Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or death.\n\nThe primary endpoint is 6-month progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate (RR), quality of life (QOL), and adverse event (AE) profiles. The study aims to enroll 196 patients across a single center in India over a period of 5 years, with an additional 6-month follow-up. This trial builds on earlier Phase II findings suggesting improved outcomes with trastuzumab in HER2-positive BTC and aims to provide the first randomized evidence for the benefit of HER2-targeted therapy in this setting.",[127,128,129,130,33],"Biliary Tract Cancer","HER2-positive Cancer","Advanced Cancer","Unresectable Biliary Tract Carcinoma","2025-07-02",{"date":133,"type":51},"2025-07-14",{"date":135,"type":51},"2023-07-21",{"date":137,"type":20},"2029-07-31",{"name":139,"class":58},"Tata Memorial Centre",6,{"id":142,"slug":143,"hasResults":11,"nctId":144,"briefTitle":145,"officialTitle":146,"acronym":4,"eligibilityCriteria":147,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":148,"targetDuration":4,"studyType":21,"phases":150,"briefSummary":151,"conditions":152,"keywords":4,"overallStatus":47,"whyStopped":4,"lastUpdateSubmitDate":179,"lastUpdatePostDateStruct":180,"startDateStruct":182,"completionDateStruct":183,"leadSponsor":185,"locationsCount":59},"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":149,"type":20},94,[71],"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.",[26,153,154,155,30,156,157,158,159,160,33,161,162,163,164,77,165,166,167,168,169,170,171,172,173,174,42,175,176,177,45,178,79],"Advanced Colorectal Carcinoma","Advanced Gastroesophageal Junction Adenocarcinoma","Advanced Lung Adenocarcinoma","Advanced Ovarian Carcinoma","Advanced Pancreatic Carcinoma","Advanced Urothelial Carcinoma","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Metastatic Colorectal Carcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","Metastatic Lung Adenocarcinoma","Metastatic Ovarian Carcinoma","Metastatic Urothelial 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 Colorectal Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Pancreatic Cancer AJCC v8","Stage IV Colorectal Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","2023-03-08",{"date":181,"type":51},"2023-03-10",{"date":179,"type":51},{"date":184,"type":20},"2030-03-04",{"name":89,"class":58}]