[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-hepatocellular-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-hepatocellular-carcinoma":69},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,13,0,[8,141,175,205,232,264,298,319,344,365,434,483,545],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":130,"startDateStruct":133,"completionDateStruct":135,"leadSponsor":137,"locationsCount":140},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958",false,"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","ALL","16 Years",{"count":20,"type":21},132,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","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.",[28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127],"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 Gastric Cancer AJCC v8","Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage III Merkel Cell Carcinoma AJCC v8","Clinical Stage IV Cutaneous Melanoma AJCC v8","Clinical Stage IV Gastric Cancer AJCC v8","Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IV Merkel Cell Carcinoma AJCC v8","Clinical Stage IVA Gastric Cancer AJCC v8","Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Clinical Stage IVB Gastric Cancer AJCC v8","Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Locally Advanced Cervical Carcinoma","Locally Advanced Endometrial Carcinoma","Locally Advanced Gastric Adenocarcinoma","Locally Advanced Gastroesophageal Junction Adenocarcinoma","Locally Advanced Head and Neck Squamous Cell Carcinoma","Locally Advanced Hepatocellular Carcinoma","Locally Advanced Lung Non-Small Cell Carcinoma","Locally Advanced 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 Gastric Adenocarcinoma","Metastatic Gastroesophageal Junction Adenocarcinoma","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 Gastric Adenocarcinoma","Unresectable Gastroesophageal Junction Adenocarcinoma","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","RECRUITING","2026-06-18",{"date":131,"type":132},"2026-06-23","ACTUAL",{"date":134,"type":132},"2022-03-31",{"date":136,"type":21},"2028-03-31",{"name":138,"class":139},"Mayo Clinic","OTHER",1,{"id":142,"slug":143,"hasResults":11,"nctId":144,"briefTitle":145,"officialTitle":146,"acronym":4,"eligibilityCriteria":147,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":149,"targetDuration":4,"studyType":22,"phases":151,"briefSummary":152,"conditions":153,"keywords":155,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":164,"lastUpdatePostDateStruct":165,"startDateStruct":167,"completionDateStruct":169,"leadSponsor":171,"locationsCount":174},"100562219","phase-1-a-study-to-evaluate-aln-bcat-in-patients-with-hepatocellular-carcinoma-100562219","NCT06600321","A Study to Evaluate ALN-BCAT in Patients With Hepatocellular Carcinoma","A Phase 1 Study of ALN-BCAT as Monotherapy and in Combination With Pembrolizumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma","Inclusion Criteria:\n\n* Has HCC confirmed histologically or cytologically, or, for patients with liver cirrhosis, clinically by the American Association for the Study of Liver Diseases (AASLD) criteria\n* Has had at least one line of systemic therapy for unresectable advanced or metastatic disease\n* Has at least one wingless-related integration site (WNT)-pathway activating mutation\n* Child-Pugh class A or B7\n\nExclusion Criteria:\n\n* Has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangio-HCC tumors\n* Has symptomatic extrahepatic disease\n* Has received anti-cancer therapy or investigational drugs ≤3 weeks prior to the first dose of study drug\n\nNote: other protocol defined inclusion \u002F exclusion criteria apply","18 Years",{"count":150,"type":21},158,[24],"The purpose of the dose escalation part of the study is to characterize the safety and tolerability of ALN-BCAT as monotherapy and in combination with pembrolizumab; and to determine the recommended dose(s) for expansion (RDFE) of ALN-BCAT as monotherapy and in combination with pembrolizumab. The purpose of the dose expansion part of the of the study is to evaluate the antitumor activity of ALN-BCAT as monotherapy and in combination with pembrolizumab; to characterize the safety and tolerability of ALN-BCAT as monotherapy and in combination with pembrolizumab.",[154,69],"Advanced Hepatocellular Carcinoma",[156,157,158,159,160,161,162,163],"Hepatocellular carcinoma (HCC)","Pembrolizumab","CTNNB1","Liver disease","Liver cancer","Liver neoplasms","Carcinoma, hepatocellular","WNT pathway activating","2026-06-16",{"date":166,"type":132},"2026-06-17",{"date":168,"type":132},"2024-12-30",{"date":170,"type":21},"2027-10-31",{"name":172,"class":173},"Alnylam Pharmaceuticals","INDUSTRY",23,{"id":176,"slug":177,"hasResults":11,"nctId":178,"briefTitle":179,"officialTitle":180,"acronym":4,"eligibilityCriteria":181,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":182,"targetDuration":4,"studyType":22,"phases":184,"briefSummary":186,"conditions":187,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":196,"lastUpdatePostDateStruct":197,"startDateStruct":199,"completionDateStruct":201,"leadSponsor":203,"locationsCount":140},"100624088","phase-4-morning-versus-afternoon-administration-of-immunotherapy-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-knight-shift-study-100624088","NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases",{"count":183,"type":21},160,[185],"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.",[188,189,154,190,191,192,193,194,68,69,70,71,72,74,195,80,81,82,97,98,99],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","2026-06-10",{"date":198,"type":132},"2026-06-12",{"date":200,"type":132},"2026-06-08",{"date":202,"type":21},"2028-12-31",{"name":204,"class":139},"OHSU Knight Cancer Institute",{"id":206,"slug":207,"hasResults":11,"nctId":208,"briefTitle":209,"officialTitle":210,"acronym":4,"eligibilityCriteria":211,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":212,"targetDuration":4,"studyType":22,"phases":214,"briefSummary":215,"conditions":216,"keywords":221,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":222,"lastUpdatePostDateStruct":223,"startDateStruct":225,"completionDateStruct":227,"leadSponsor":229,"locationsCount":231},"100610394","phase-1-symbiotic-gi-13-a-study-to-learn-about-study-medicine-called-pf-08634404-as-a-single-treatment-and-combination-treatment-in-adult-participants-with-a-liver-cancer-called-hepatocellular-carcinoma-that-is-too-advanced-to-be-removed-by-surgery-and-may-have-spread-to-other-parts-of-the-body-100610394","NCT07227012","Symbiotic-GI-13: A Study to Learn About Study Medicine Called PF-08634404 as a Single Treatment and Combination Treatment in Adult Participants With a Liver Cancer Called Hepatocellular Carcinoma, That is Too Advanced to be Removed by Surgery and May Have Spread to Other Parts of the Body.","AN INTERVENTIONAL OPEN-LABEL PHASE 1B\u002F2 STUDY TO EVALUATE SAFETY, PHARMACOKINETICS, AND PRELIMINARY EFFICACY OF PF-08634404 AS MONOTHERAPY AND COMBINATION THERAPY IN ADULT PARTICIPANTS WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC HEPATOCELLULAR CARCINOMA","Inclusion Criteria:\n\n* 18 years of age or older at screening.\n* Locally advanced or metastatic HCC with diagnosis confirmed by histology\u002Fcytology or clinically by AASLD criteria (for patients with cirrhosis). Participants without cirrhosis require histological confirmation of diagnosis.\n* Disease that is not amenable to curative surgical and\u002For locoregional therapies, or progressive disease after surgical and\u002For locoregional therapies.\n* At least 1 measurable (as defined by RECIST 1.1 per investigator) and untreated lesion.\n* Adequate hepatic, liver, and renal function\n* No prior systemic therapy for HCC.\n* ECOG performance status 0 or 1\n* Child-Pugh Class A\n\nKey Exclusion Criteria:\n\n* Moderate or severe ascites.\n* History of hepatic encephalopathy.\n* Participants with known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression.\n* Clinically significant risk of hemorrhage or fistula.\n* Participants with any history of another malignancy within 3 years.\n* History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.\n* Participants with active autoimmune diseases requiring systemic treatment within the past 2 years.\n* Clinically significant cardiovascular disease within 6 months prior to the first dose.\n* Major surgery or severe trauma within 4 weeks prior to the first dose or planned major surgery during the study.\n* History of severe bleeding tendency or coagulation dysfunction.\n* History of severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding, including bleeding event due to esophageal and\u002For gastric varices, within 6 months prior to the first dose.\n* Participants with acute, chronic or symptomatic infections.\n* Participants with history of immunodeficiency.",{"count":213,"type":21},138,[24,25],"The purpose of this study is to learn about the effects of study medicine (PF-08634404) when given alone or with another antibody (ipilimumab) for the treatment of a type of liver cancer called hepatocellular carcinoma (HCC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body.\n\nTo join the study, participants must meet the following conditions:\n\n* Be 18 years or older.\n* Have locally advanced or metastatic HCC.\n* Is not a candidate for complete surgical or loco-regional therapies.\n* Have not received any whole-body treatment for HCC.\n\nParticipants will receive PF-08634404 either alone or in combination with ipilimumab. The medicine will be given through intravenous (IV) infusions, which means it will be administered directly into a vein. All treatments will take place at clinical trial sites, where trained medical staff will monitor participants during and after each visit.",[217,218,219,114,220,154,69],"Carcinoma, Hepatocellular","Hepatocellular Cancer","Hepatocellular Carcinoma","Liver Neoplasms",[219,160,220],"2026-06-03",{"date":224,"type":132},"2026-06-04",{"date":226,"type":132},"2025-12-01",{"date":228,"type":21},"2028-10-17",{"name":230,"class":173},"Pfizer",35,{"id":233,"slug":234,"hasResults":11,"nctId":235,"briefTitle":236,"officialTitle":237,"acronym":4,"eligibilityCriteria":238,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":239,"enrollmentInfo":240,"targetDuration":4,"studyType":22,"phases":242,"briefSummary":243,"conditions":244,"keywords":251,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":222,"lastUpdatePostDateStruct":256,"startDateStruct":257,"completionDateStruct":259,"leadSponsor":261,"locationsCount":140},"100521172","phase-1-a-study-of-therapeutic-drug-monitoring-based-atezolizumab-dosing-100521172","NCT06066138","A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing","A Feasibility Phase I Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing","* INCLUSION CRITERIA:\n* Participants with a locally advanced or metastatic pathologically confirmed cancer whose NCI Licensed Independent Practitioner (LIP) determined they are candidates for treatment with atezolizumab, either alone or in combination with other FDA-approved drug(s), for example, TMB-high, PDL-1 positive, or other disease states that respond to PD(L)-1 inhibitors. Regimens with atezolizumab alone or in combination with agents that have previously demonstrated safety in published clinical trials may be used. An LIP may be either an MD, DO, PA, or NP and must be qualified for oncologic management per institutional practice.\n* Age \\>=18 years old.\n* Measurable disease per RECIST 1.1 criteria.\n* ECOG performance status of 0-2.\n* Participants must have adequate organ and marrow function as defined below:\n\n  * Absolute neutrophil count (ANC) \\>=1,200\u002Fmicroliter\n  * Hemoglobin \\>9.0 g\u002FdL\n  * Platelets \\>=75,000\u002Fmicroliter\n  * Total bilirubin \\\u003C= 1.5 mg\u002FdL, except in participants with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg\u002FdL\n  * Aspartate aminotransferase (AST) \u002F Alanine aminotransferase (ALT) \\\u003C=2.5 X institutional upper limit of normal (ULN)\n  * Creatinine Clearance (CrCl) \\>=30 mL\u002Fmin\u002F1.73 m\\^2 (calculated using the Cockcroft-Gault formula).\n  * Serum albumin \\> 3 g\u002FdL\n* Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization) for the duration of the study treatment and up to 5 months after the last dose of the atezolizumab (restriction period). NOTE: abstinence, defined as no vaginal heterosexual intercourse within 6 months prior to the treatment initiation and willingness to continue abstinence for restriction period is also acceptable.\n\nIndividuals who can father children must agree to use an effective method of contraception (barrier, surgical sterilization) at study entry and up to 5 months after the last dose of the atezolizumab.\n\n* Nursing participants must be willing to discontinue nursing from study treatment initiation through 5 months after atezolizumab treatment discontinuation.\n* Participants with history of human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and have undetectable viral load.\n* Participants with history of chronic hepatitis B virus (HBV) infection must be on suppressive therapy, if indicated, and have undetectable HBV viral load.\n* Participants with history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load.\n* Participants with history of treated brain metastases must have follow-up brain imaging after central nervous system (CNS)-directed therapy with no evidence of progression.\n* Participants 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.\n* All participants must have the ability to understand and willingness to sign a written informed consent.\n\nEXCLUSION CRITERIA:\n\nParticipants who have received an investigational agent for treating participants' disease not approved by FDA within 28 days prior to study treatment initiation.\n\n* Participants who have received immunostimulatory agents, including, but not limited to, IFN-alpha, IFN-gamma, or IL-2, immunosuppressive medications, and any herbal medicines within 1 month prior to study treatment initiation. NOTE: Physiologic doses of systemic steroids (\\\u003C= 10 mg prednisone or equivalent) or local (e.g., topical, nasal, intraarticular, inhaled) steroid use is permitted.\n* Prior treatment with CD137 agonists\n* Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies; (including atezolizumab) within 28 days prior to study treatment initiation.\n* History or risk of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:\n\n  * Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone.\n  * Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen.\n  * Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis would be excluded) are permitted provided all of the following conditions are met:\n\n    * Rash must cover less than 10% of body surface area (BSA)\n    * Disease is well controlled at screening and only requiring low potency topical steroids\n    * No acute exacerbations of underlying condition within 12 months prior to study treatment initiation (not requiring psoralen plus ultraviolet A radiation \\[PUVA\\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids) within 12 months prior to study treatment initiation.\n* Persisting toxicity related to prior therapy of Grade \\>1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 unless deemed not clinically significant or irreversible. NOTE: alopecia and sensory neuropathy Grade \\\u003C= 2 are acceptable.\n* Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation.\n* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation\n* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment\n* Active tuberculosis at screening\n* History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Participants with significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident (https:\u002F\u002Fwww.heart.org\u002Fen\u002Fhealth-topics\u002Fheart-failure\u002Fwhat-isheart-failure\u002Fclasses-of-heart-failure), unstable arrhythmia, or unstable angina within 3 months prior to study treatment initiation.\n* Pregnancy (confirmed with Beta-Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in IOCBP performed at screening).\n* Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.","120 Years",{"count":241,"type":21},30,[24],"Background:\n\nA type of drug called monoclonal antibody immune checkpoint inhibitors are often used in cancer treatment. These drugs help the body s immune system fight cancer by blocking proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved to treat certain cancers. Researchers want to find out if lower doses of this drug might provide the same benefit with fewer adverse effects.\n\nObjective:\n\nTo test different doses and timing of atezolizumab for people with cancer.\n\nEligibility:\n\nPeople aged 18 years and older with cancer that has spread locally or to other organs. They must be eligible for treatment with the study drug.\n\nDesign:\n\nParticipants will be screened. They will have blood tests and imaging scans. They will provide a sample of tissue from their tumor.\n\nAtezolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will take this drug alone or combined with other drugs prescribed for their care.\n\nThe first 2 treatments will be done per the FDA recommended dose and schedule. Before administering the second dose of the study drug, researchers will check the level of the drug in the participant s blood. Depending on those results, their 3rd dose will be scheduled 2 to 6 weeks later.\n\nFor the 3rd dose of the study drug, participants will switch to the FDA minimum dosage. Dosages of any other drugs will not change.\n\nResearchers will continue to test the levels of the drug in participants blood before each treatment for 16 weeks. After that, these levels will be tested every 3 months.\n\nStudy treatment may last up to 2 years.",[245,246,247,248,249,250,50,69,53,72],"Locally Advanced Alveolar Soft Part Sarcoma","Metastatic Alveolar Soft Part Sarcoma","Locally Advanced Non Small Cell Lung Cancer","Metastatic Non Small Cell Lung Cancer","Locally Advanced Small Cell Lung Cancer","Metastatic Small Cell Lung Cancer",[252,253,254,255],"PD-L1","PD-1","Tecentriq","Immunotherapy",{"date":224,"type":132},{"date":258,"type":132},"2025-11-04",{"date":260,"type":21},"2028-01-31",{"name":262,"class":263},"National Cancer Institute (NCI)","NIH",{"id":265,"slug":266,"hasResults":11,"nctId":267,"briefTitle":268,"officialTitle":269,"acronym":4,"eligibilityCriteria":270,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":271,"targetDuration":4,"studyType":22,"phases":273,"briefSummary":274,"conditions":275,"keywords":280,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":289,"lastUpdatePostDateStruct":290,"startDateStruct":291,"completionDateStruct":293,"leadSponsor":295,"locationsCount":297},"100548972","phase-1-a-phase-1-study-of-bgb-b2033-alone-or-in-combination-with-tislelizumab-with-or-without-bevacizumab-in-participants-with-advanced-or-metastatic-solid-tumors-100548972","NCT06427941","A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Advanced or Metastatic Solid Tumors","A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Selected Advanced or Metastatic Solid Tumors","Key Inclusion Criteria:\n\n1. Participants must have one of the following unresectable, locally advanced, or metastatic tumor types:\n\n   1. Hepatocellular carcinoma (HCC): Histologically or cytologically confirmed HCC that is either Barcelona Clinic Liver Cancer (BCLC) Stage C, or BCLC Stage B that is not amenable to, or has progressed after, loco-regional therapy and is not eligible for a curative treatment approach.\n   2. Alpha-fetoprotein (AFP)-producing gastric cancer (GC): Histologically confirmed GC with AFP \\> 20 ng\u002FmL in blood or tumor tissue positive for AFP by a validated immunohistochemistry (IHC) assay based on local or central testing.\n   3. Germ cell tumors: Histologically confirmed germ cell tumors including extragonadal yolk sac tumors (e.g., located in the mediastinum, vagina, brain, retroperitoneum), and non-dysgerminomas for which no further curative systemic treatment options exist.\n   4. Glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC): Histologically confirmed GPC3-positive squamous NSCLC with prior exposure to a checkpoint inhibitor (CPI).\n2. At least one evaluable lesion for dose escalation, and\n3. At least one measurable lesion for safety expansion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.\n4. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.\n5. Adequate organ function as defined in the protocol.\n6. Provision of tumor tissue samples is required for specified parts of the study.\n\nKey Exclusion Criteria:\n\n1. Prior therapy directed against glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (CD137).\n2. Active leptomeningeal disease or uncontrolled\u002Funtreated brain metastases.\n3. Active autoimmune disease or a history of autoimmune disease with potential for relapse.\n4. Any malignancy diagnosed ≤ 2 years before the first dose of study drug(s), except: The cancer type under investigation in this study, or Locally recurring malignancies previously treated with curative intent.\n5. Requirement for systemic corticosteroids (\\> 10 mg\u002Fday prednisone or equivalent) or other immunosuppressive therapy within 14 days prior to the first dose of study drug(s).\n6. Certain comorbidities involving the lungs, heart, bleeding conditions, or active infections, as defined in the protocol.\n\nNote: Additional protocol-defined inclusion and exclusion criteria may apply.",{"count":272,"type":21},392,[24],"This is a first-in-human (FIH) clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of BGB-B2033 administered as monotherapy and in combination with tislelizumab, with or without bevacizumab. The study will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors\u002Fnon-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC).",[69,276,277,278,279],"Local Advanced Hepatocellular Carcinoma","Alpha-fetoprotein (AFP)-Producing Gastric Cancer","Extragonadal Yolk Sac Tumors","Glypican-3 (GPC3)-Positive Squamous Non-small Cell Lung Cancer",[281,282,283,284,285,286,287,288],"GPC-3","GPC3-positive squamous non-small cell lung cancer","BGB-B2033","tislelizumab","hepatocellular carcinoma","alpha-fetoprotein (AFP)-producing gastric cancer","extragonadal yolk sac tumors","Bevacizumab","2026-06-01",{"date":222,"type":132},{"date":292,"type":132},"2024-07-23",{"date":294,"type":21},"2028-05-30",{"name":296,"class":173},"BeOne Medicines",46,{"id":299,"slug":300,"hasResults":11,"nctId":301,"briefTitle":302,"officialTitle":303,"acronym":4,"eligibilityCriteria":304,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":305,"targetDuration":4,"studyType":22,"phases":307,"briefSummary":308,"conditions":309,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":310,"lastUpdatePostDateStruct":311,"startDateStruct":313,"completionDateStruct":315,"leadSponsor":317,"locationsCount":318},"100578424","phase-1-testing-the-addition-of-an-anti-cancer-drug-sapanisertib-to-the-usual-chemotherapy-treatment-cabozantinib-in-metastatic-liver-cell-cancer-with-a-change-in-genes-for-the-protein--catenin-the-saphire-trial-100578424","NCT06811116","Testing the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial","A Phase I\u002FII Trial of Sapanisertib in Combination With Cabozantinib in β-catenin-mutated Hepatocellular Carcinoma (SAPHIRE)","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed HCC, not amenable to curative treatment approach\n* For Phase 2, patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam\n* For phase 2, patients must have a β-catenin mutation, based on next generation eequencing (NGS) testing through Clinical Laboratory Improvement Amendments (CLIA)-certified commercially available standard of care assay\n* Patients must have received at least one prior line of systemic therapy in the metastatic setting, including a prior immune checkpoint inhibitor therapy unless not eligible. For the phase 2 portion, patients must have received at least one and no more than two prior lines of systemic therapy in the metastatic setting, including a prior immune checkpoint inhibitor therapy unless not eligible\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of sapanisertib in combination with cabozantinib in patients \\\u003C18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)\n* Child Pugh score of A\n* Absolute neutrophil count ≥ 1,000\u002FmcL\n* Platelets ≥ 30,000\u002FmcL\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 5 × institutional ULN\n* Glomerular filtration rate (eGFR) ≥ 40 mL\u002Fmin\u002F1.73 m\\^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* For the phase 2 portion, availability of archival tumor tissue at the time of patient enrollment for banking for molecular profiling studies\n* The effects of sapanisertib and cabozantinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and after completion of drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Both men and women treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and for the following duration after completion of sapanisertib and cabozantinib administration:\n\n  * 90 days and 120 days after last dose of sapanisertib for women of childbearing potential and men respectively,\n  * 5 months and 7 months after last dose of cabozantinib for women of childbearing potential and men respectively\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to sapanisertib and cabozantinib\n* Use of strong CYP3A4-inhibiting agents due to drug-drug interaction with cabozantinib\n* Prior exposure to cabozantinib\n* Patients who are unable to swallow oral medications such as capsules and tablets and patients with gastrointestinal conditions that may affect the absorption of oral medications\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because sapanisertib and cabozantinib have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sapanisertib and cabozantinib, breastfeeding should be discontinued if the mother is treated with sapanisertib and cabozantinib",{"count":306,"type":21},92,[24,25],"This phase I\u002FII trial studies the side effects and best dose of sapanisertib when given together with cabozantinib, and to see how well they work in treating patients with liver cancer that has spread from where it first started to other places in the body (metastatic) and contains a mutation (change) in the β-catenin gene. Sapanisertib and cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sapanisertib and cabozantinib together may work better than giving cabozantinib alone in treating β-catenin-mutated metastatic hepatocellular carcinoma.",[154,69,80,97],"2026-05-12",{"date":312,"type":132},"2026-05-13",{"date":314,"type":132},"2025-11-17",{"date":316,"type":21},"2027-08-31",{"name":262,"class":263},4,{"id":320,"slug":321,"hasResults":11,"nctId":322,"briefTitle":323,"officialTitle":324,"acronym":4,"eligibilityCriteria":325,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":239,"enrollmentInfo":326,"targetDuration":4,"studyType":22,"phases":328,"briefSummary":329,"conditions":330,"keywords":331,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":336,"lastUpdatePostDateStruct":337,"startDateStruct":339,"completionDateStruct":341,"leadSponsor":343,"locationsCount":140},"100439561","phase-1-gpc3-targeted-car-t-cell-therapy-in-advanced-gpc3-expressing-solid-tumor-malignancies-100439561","NCT05003895","GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies","Phase I Study of GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies","* INCLUSION CRITERIA:\n* Histopathological confirmation of HCC or other solid tumor malignancy by the NCI Laboratory of Pathology\n* Participants must:\n\n  * have progressed on at least 1 prior line of treatment\n\nOR\n\n--been intolerant of at least 1 prior line of treatment.\n\n* Participants must have at least 1 focus of disease that is amenable to mandatory tumor biopsy prior to study treatment initiation to determine tumor GPC3 expression and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators.\n* Tumor must have GPC3 positivity of \\>= 25% by immunohistochemistry on freshly collected biopsy\n* Participants must have at least 1 measurable lesion by RECIST version 1.1\n* Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation.\n* Age \\>= 18 years.\n* Performance status (ECOG) 0-1\n* Participants must have adequate organ and marrow function as defined below:\n\nANC: \\>= 1,000\u002FmcL\n\nPlatelets: \\>= 75,000\u002FmcL\n\nHemoglobin: \\>= 8 g\u002FdL\n\ntotal bilirubin: If cirrhosis present: Part of Child Pugh requirement\n\nIf no cirrhosis: bilirubin should be \\\u003C= 1.5 x ULN\n\nALT or AST: \\\u003C= 5 x ULN.\n\nCreatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl) (A): \\\u003C 1.5x institution upper limit of normal OR \\>= 50 mL\u002Fmin\u002F1.73 m\\^2 for participant with creatinine levels, \\>= 1.5 X institutional ULN\n\nALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase);\n\nAST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.\n\n(A)Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.\n\n* Normal cardiac ejection fraction (\\>= 50% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks before treatment initiation.\n* Room air oxygen saturation of 92% or greater.\n* Treatment-related toxicities must be resolved to \\\u003C= grade 1.\n* For participants with brain metastases: Participants with \\\u003C=3 (three or fewer) brain metastases that have been treated with surgery or stereotactic radiosurgery or other form of treatment are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment.\n* The study drugs are harmful to developing human fetus. For this reason, women of childbearing potential must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drugs. We also recommend men with partners of childbearing potential ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men must not freeze or donate sperm within the same period.\n* HBV infected participants must be on antivirals and have HBV DNA \\\u003C 100IU\u002FmL. HCV infected participants can be enrolled with close HCV RNA level monitoring.\n* Participants must be able to understand and be willing to sign a written informed consent.\n* For participants that do not have a legally authorized representative in place, one must be identified before study treatment starts\n\nExclusion Criteria\n\n* Prior systemic therapy, an investigational therapy, radiation, and\u002For surgery within 2 weeks prior to treatment initiation.\n* Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation.\n* Child-Pugh class B or C liver function\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\nNote: Participants with a history of abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible per PI discretion.\n\n* Any form of primary immunodeficiency (e.g. severe combined immunodeficiency).\n* HIV-positive participants are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these participants.\n* Participants receiving systemic steroids \\>= 0.5 mg prednisone equivalent\u002Fkg\u002Fday. Steroid creams, ointments, and eye drops are allowed. Dose adjustment or discontinuation of medication must occur at least 24 hours prior to conditioning chemotherapy. Use of CART cell therapy in autoimmune diseases has the potential to be associated with serious safety risk. Given that this is an evolving area of research, caution should be exercised and any decision to include participants with autoimmune diseases should be made on a case-bycase basis.\n* History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.\n* Hospitalization within 7 days prior to treatment initiation.\n* Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs.\n* Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of study therapy\n* Participants with a history of seizure disorder\n* Participants with an expected life expectancy of less than 3 months before initiation of study therapy.",{"count":327,"type":21},38,[24],"Background:\n\nA new cancer treatment takes a person s own T cells, modifies them in a laboratory so they can better fight cancer cells, and then gives them back to the person. Researchers want to see if this treatment can help people with a certain types of cancer.\n\nObjective:\n\nTo see if a personalized immune treatment, anti-GPC3 CAR-T cells, is safe.\n\nEligibility:\n\nAdults aged 18 years and older who have Glypican-3 (GPC3) positive solid tumor malignancy.\n\nDesign:\n\nParticipants will be screened with the following:\n\nBlood and urine tests\n\nMedical history\n\nPhysical exam\n\nHeart function tests\n\nReview of their symptoms and their ability to perform their normal activities\n\nTumor biopsy\n\nImaging scan of the chest, abdomen, and pelvis\n\nParticipants will have leukapheresis. They may have an IV (intravenous catheter, a small tube put into an arm vein) inserted into each arm or get a central line. Blood will be removed. A machine will separate the white blood cells from their blood. The rest of their blood will be returned to them.\n\nParticipants will be admitted to the hospital for about 2 weeks. They will get the chemotherapy drugs fludarabine and cyclophosphamide by IV for 3 days. Then they will receive the modified white blood cells by IV.\n\nParticipants will have frequent blood draws. They will give blood and tumor samples for research.\n\nParticipants will have follow-up visits for the next 15 years. Then they will be contacted by email or phone for the rest of their life. If their disease does not get worse after 5 years, they will continue to be invited to do imaging studies every 6 months.",[219,218,69],[332,333,334,335],"immuno therapy","Targeted Therapy","Leukapheresis","Gene Therapy","2026-04-04",{"date":338,"type":132},"2026-04-07",{"date":340,"type":132},"2021-12-08",{"date":342,"type":21},"2027-12-31",{"name":262,"class":263},{"id":345,"slug":346,"hasResults":11,"nctId":347,"briefTitle":348,"officialTitle":349,"acronym":4,"eligibilityCriteria":350,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":351,"targetDuration":4,"studyType":22,"phases":353,"briefSummary":354,"conditions":355,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":356,"lastUpdatePostDateStruct":357,"startDateStruct":359,"completionDateStruct":361,"leadSponsor":363,"locationsCount":318},"100606362","phase-2-celecoxib-durvalumab-and-tremelimumab-for-the-treatment-of-patients-with-advanced-or-metastatic-liver-cancer-100606362","NCT07174570","Celecoxib, Durvalumab and Tremelimumab for the Treatment of Patients With Advanced or Metastatic Liver Cancer","Repurposing Celecoxib to Overcome Resistance to Immunotherapy in Advanced HCC (RECON Study)","Inclusion Criteria:\n\n* Histologically or cytologically confirmed hepatocellular cancer (HCC) planned for treatment at gastrointestinal clinics of Emory University's Winship Cancer Institute or Grady Cancer Center\n* Radiologically measurable disease based on Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1\n* Age ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Platelet count \\> 100,000 cells\u002F ul (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Hemoglobin (Hb) \\> 9g\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Absolute neutrophil count \\> 1000 cells\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Albumin \\> 3g\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Total bilirubin \\\u003C 3mg\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Glomerular filtration rate (GFR) \\> 60ml\u002Fmin (based on creatine, and cystatin C estimation where applicable) (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy\n* FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n\n  \\* A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n* Completion of all previous cancer directed therapy (including, radiotherapy, liver lesion ablation, bland or chemoembolization and transarterial radioembolization therapy) ≥ 4 weeks before the start of study therapy.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class IIB or better.\n\n  * Patients without existing cardiac disease that could raise the risk of complications who consent for the trial will proceed with trial participation\n  * Patients with existing cardiac disease that could raise the risk of complications will be referred at the discretion of the investigator to a cardio-oncologist or general cardiologist for cardiac optimization prior to starting celecoxib\n* Life expectancy \\> 12 weeks as determined by the investigator\n* Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. This includes willingness to undergo mandatory blood sample draws for evaluation of correlatives\n* Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.\n\nExclusion Criteria:\n\n* Mild to moderate liver dysfunction evidenced by Child Pugh score 7B and above\n* History of arterial or venous thromboembolic events or gastrointestinal bleeding event. Subjects with portal venous thrombosis are permitted in the study if their treating oncologist does not deem it necessary to treat this with heparin products or direct acting anticoagulant (DOAC)\n* Current use of warfarin, heparin products and DOACs\n* Subjects with a history of (non-bleeding) peptic ulcer disease who have been on a proton pump inhibitor for less than 30 days prior to screening visit\n* Patients who have had immune checkpoint inhibitors (ICI) therapy within 6 months prior to entering the study or those who have not recovered from adverse events due to liver directed therapy administered more than 4 weeks earlier (i.e., have residual toxicities \\> grade 2)\n* Patients who are receiving any other investigational agents or an investigational device within 28 days before administration of first dose of study drugs\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study\n* Contraindication to ICI per investigator discretion\n* Uncontrolled current 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* Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; or uncontrolled grade ≥ 3 hypertension (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥ 160 mmHg) despite antihypertensive therapy\n* Contraindication to non-steroidal anti-inflammatory drugs (NSAIDs): cardiac conditions that significantly raise the risk of cardiopulmonary complications, including unstable angina, uncontrolled heart failure, recent gastrointestinal (GI) bleed. Note that patients who are stable on low dose aspirin (\\\u003C 325mg\u002Fday) only will be allowed on study\n* Current use of other NSAIDs.",{"count":352,"type":21},39,[25],"This phase II trial tests how well the combination of celecoxib with durvalaumab and tremellimumab works in treating patients with hepatocellular cancer (liver cancer) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents and is used to reduces pain. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving celecoxib with durvalaumab and tremellimumab may better treat patients with advanced or metastatic liver cancer.",[154,69,80,97],"2026-01-26",{"date":358,"type":132},"2026-01-28",{"date":360,"type":132},"2026-01-02",{"date":362,"type":21},"2027-11-13",{"name":364,"class":139},"Emory University",{"id":366,"slug":367,"hasResults":11,"nctId":368,"briefTitle":369,"officialTitle":369,"acronym":4,"eligibilityCriteria":370,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":371,"targetDuration":4,"studyType":22,"phases":373,"briefSummary":374,"conditions":375,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":425,"lastUpdatePostDateStruct":426,"startDateStruct":428,"completionDateStruct":430,"leadSponsor":432,"locationsCount":140},"100446356","phase-1-phase-i-study-of-tumor-treating-fields-ttf-in-combination-with-cabozantinib-or-with-pembrolizumab-and-nab-paclitaxel-in-patients-with-advanced-solid-tumors-involving-the-abdomen-or-thorax-100446356","NCT05092373","Phase I Study of Tumor Treating Fields (TTF) in Combination With Cabozantinib or With Pembrolizumab and Nab-Paclitaxel in Patients With Advanced Solid Tumors Involving the Abdomen or Thorax","Inclusion Criteria:\n\n* Participants must have pathologically confirmed advanced\u002Fmetastatic solid cancer (hepatocellular carcinoma, renal cell carcinoma, breast cancer, ovarian\u002Ffallopian, or endometrial\u002Fprimary peritoneal tumors) involving the abdomen or thorax, cannot tolerate standard therapy or have experienced tumor progression on standard therapy.\n* Age: ≥18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.\n* Life expectancy \\>3 months.\n* Normal bone marrow function, defined as absolute neutrophil count ≥1,000\u002FµL; platelets ≥75,000\u002FµL; hemoglobin ≥8 g\u002FdL.\n* Adequate hepatic function as defined by a total bilirubin level ≤1.5 x the upper limit of normal (ULN), unless the patient has known Gilbert's syndrome, and alanine aminotransferase (ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤2.5 x ULN (unless the patient has liver metastases: ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤5 x ULN).\n* Participants with HCC must have a Child Pugh status A, no clinically significant ascites (requiring pharmacological or interventional treatment), and no history (or increased risk) of esophageal\u002Fgastric bleeding, impaired wound healing, perforation or fistula.\n* Serum creatinine clearance ≥50 mL\u002Fmin by the Cockcroft-Gault formula.\n* Measurable disease by RECIST or evaluable disease.\n* Contraception: Women of childbearing potential 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. Childbearing potential will be defined as women who have had menses within the past 12 months and who have not had a tubal ligation, hysterectomy, or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. Male participants must agree to use effective contraception or abstinence while on study.\n* Able to operate the TTF device independently or with the help of a caregiver.\n\nExclusion Criteria:\n\n* Participants must not receive prior anticancer therapy or radiation therapy within 2 weeks and must not undergo major surgery within 4 weeks prior to initiation of treatment on protocol. Participants who are already on cabozantinib and have progressive disease are allowed to transition to treatment with tumor treating fields and cabozantinib. Participants in both cohorts who already started treatments as standard of care (Cohort 1: Cabozantinib and Cohort 2: nab-paclitaxel and Pembrolizumab) are allowed to start on protocol within the first 2-3 weeks of treatment initiation. Palliative radiation therapy is allowed.\n* Participants must have recovered to Grade 0-1 toxicity from prior therapy.\n* Active brain metastasis or leptomeningeal disease. Patients with treated brain metastasis must have stable disease, evidenced by brain imaging for at least 4 weeks and the patient must have been off steroids for at least 2 weeks.\n* The patient has cardiac conditions as follows: uncontrolled: hypertension (blood pressure \\[BP\\] \\> 160\u002F100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association Class II or above), prior or current cardiomyopathy, uncontrolled atrial fibrillation with heart rate \\> 100 beats per minute (bpm), unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment or angina requiring use of nitrates more than once weekly).\n* The patient has concurrent severe and\u002For uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease).\n* Concurrent malignancies are permitted if (A) they were previously treated, and all treatment of that malignancy was completed at least 2 years before enrollment and no evidence of disease exists, or (B) with agreement from the Principal Investigator (PI), participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible to participate if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low, or (C) with agreement from the PI, other malignancies may be permitted if the risk of the prior malignancy interfering with either safety or efficacy end points is very low. Adequately treated basal or squamous cell carcinoma or carcinoma in situ is allowed.\n* The patient is pregnant or breastfeeding.\n* History of hypersensitivity or contraindication to TTF.\n* Implanted pacemaker, defibrillator or other electrical medical devices.\n* The participant has a previously-identified allergy or hypersensitivity to cabozantinib, nab-paclitaxel, or pembrolizumab, medical adhesives or hydrogel or the patient has received prior cabozantinib and discontinued therapy due to unacceptable toxicity.\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.\n* The patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.\n* CABOZANTINIB COHORT ONLY: The patient has experienced clinically-significant hematemesis or hemoptysis of \\> 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel.\n* CABOZANTINIB COHORT ONLY: The patient has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has prothrombin time\u002Finternational normalized ratio (PT\u002FINR) or partial thromboplastin time (PTT) test results that are above (1.3X) the laboratory upper limit of normal.\n* CABOZANTINIB COHORT ONLY: The subject has a corrected QT interval (QTcF) \\> 450 ms for men or \\> 470 ms for women.\n* CABOZANTINIB COHORT ONLY: The patient requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents. Low-dose aspirin (≤ 81 mg\u002Fday), low dose warfarin (≤ 1mg\u002Fday), and prophylactic low molecular weight heparin (LMWH) are permitted.\n* CABOZANTINIB COHORT ONLY: Patients with encasement of a major artery or bowel by tumor are excluded.\n* CABOZANTINIB COHORT ONLY: The patient is unable to swallow capsules.\n* CABOZANTINIB COHORT ONLY: History of hypersensitivity or contraindication to cabozantinib.\n* ATEZOLIZUMAB-CONTAINING COHORT: Participants who have received prior immunotherapy, including prior anti-PD-1 or anti-PD-L1 therapies may participate: (A) only if their prior anti-PD-1 or anti-PDL1 monotherapy or combination therapy were NOT the last treatment prior to participation on this study. (B) Participants who had prior immunotherapies and experienced Grade 1-2 immune-related adverse event (irAE) must have documentation that their irAEs are Grade 1 or 0 using current Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and participants must be off steroid therapy and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 14 days from Cycle 1, Day 1. (C) Participants who experienced Grade 3 irAEs consisting of laboratory abnormalities that were asymptomatic and have now resolved to Grade 1 or 0 and participants who have been off steroid and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 30 days from Cycle 1, Day 1. Participants with prior irAE pneumonitis (\\>= Grade 2) should not be given atezolizumab.\n* ATEZOLIZUMAB-CONTAINING COHORT: Human immunodeficiency virus (HIV) infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics.\n* ATEZOLIZUMAB-CONTAINING COHORT: Has received a live vaccine within 30 days prior to first dose.\n* ATEZOLIZUMAB-CONTAINING COHORT: Active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.\n* ATEZOLIZUMAB-CONTAINING COHORT: Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g. Wegener's Granulomatosis) are excluded from this study.\n* ATEZOLIZUMAB-CONTAINING COHORT: History of\u002For current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.",{"count":372,"type":21},43,[24],"This phase Ib trial tests the safety, side effects, and best dose of tumor treating fields therapy in combination with either cabozantinib or nab-paclitaxel and atezolizumab in treating patients with solid tumors involving the abdomen or thorax that have spread to other parts of the body (advanced). Tumor treating fields therapy on this study utilizes NovoTTF systems that are wearable devices that use electrical fields at different frequencies that may help stop the growth of tumor cells by interrupting cancer cells' ability to divide. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tumor treating fields therapy in combination with either cabozantinib, or with nab-paclitaxel and atezolizumab may help control advanced solid tumors involving the abdomen or thorax.",[376,377,378,154,379,380,381,382,383,193,28,29,30,31,32,384,385,386,65,387,69,388,389,390,391,392,74,393,394,395,396,397,398,80,399,400,82,401,402,84,403,404,86,405,406,407,408,409,88,410,411,90,412,413,414,92,93,94,415,97,416,417,99,418,419,101,420,421,103,422,105,423,424,107],"Advanced Breast Carcinoma","Advanced Endometrial Carcinoma","Advanced Fallopian Tube Carcinoma","Advanced Malignant Abdominal Neoplasm","Advanced Malignant Female Reproductive System Neoplasm","Advanced Malignant Thoracic Neoplasm","Advanced Ovarian Carcinoma","Advanced Primary Peritoneal Carcinoma","Malignant Abdominal Neoplasm","Malignant Solid Neoplasm","Metastatic Breast Carcinoma","Metastatic Fallopian Tube Carcinoma","Metastatic Malignant Abdominal Neoplasm","Metastatic Malignant Female Reproductive System Neoplasm","Metastatic Malignant Thoracic Neoplasm","Metastatic Ovarian Carcinoma","Metastatic Primary Peritoneal Carcinoma","Prognostic Stage III Breast Cancer AJCC v8","Prognostic Stage IIIA Breast Cancer AJCC v8","Prognostic Stage IIIB Breast Cancer AJCC v8","Prognostic Stage IIIC Breast Cancer AJCC v8","Prognostic Stage IV Breast Cancer AJCC v8","Stage III Fallopian Tube Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Primary Peritoneal Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Fallopian Tube Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Primary Peritoneal Cancer AJCC v8","Stage IIIA1 Fallopian Tube Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Fallopian Tube Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Fallopian Tube Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Primary Peritoneal Cancer AJCC v8","Stage IIIC Fallopian Tube Cancer AJCC v8","Stage IIIC Ovarian Cancer AJCC v8","Stage IIIC Primary Peritoneal Cancer AJCC v8","Stage IV Fallopian Tube Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Primary Peritoneal Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Fallopian Tube Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Primary Peritoneal Cancer AJCC v8","Stage IVB Fallopian Tube Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Primary Peritoneal Cancer AJCC v8","2026-01-13",{"date":427,"type":132},"2026-01-14",{"date":429,"type":132},"2022-04-29",{"date":431,"type":21},"2026-09-01",{"name":433,"class":139},"M.D. Anderson Cancer Center",{"id":435,"slug":436,"hasResults":11,"nctId":437,"briefTitle":438,"officialTitle":439,"acronym":440,"eligibilityCriteria":441,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":442,"targetDuration":4,"studyType":22,"phases":444,"briefSummary":445,"conditions":446,"keywords":460,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":473,"lastUpdatePostDateStruct":474,"startDateStruct":476,"completionDateStruct":478,"leadSponsor":480,"locationsCount":482},"100586467","phase-1-safety-and-preliminary-anti-tumor-activity-of-tyra-430-in-advanced-hepatocellular-carcinoma-and-other-solid-tumors-with-activating-fgffgfr-pathway-aberrations-100586467","NCT06915753","Safety and Preliminary Anti-Tumor Activity of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF\u002FFGFR Pathway Aberrations","A Multicenter, Open-label, First-in-Human Study of TYRA-430 in Advanced Hepatocellular Carcinoma and Other Solid Tumors With Activating FGF\u002FFGFR Pathway Aberrations","SURF431","Key Inclusion Criteria:\n\nAll Patients:\n\n* Age ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.\n* Adequate end organ function.\n* Ability to swallow oral formulations.\n* Ability to understand and willingness to sign the ICF.\n\nPart A:\n\n* Histologically confirmed locally advanced unresectable\u002Fmetastatic HCC or histologically confirmed advanced solid tumor with documented FGF\u002FFGFR pathway alterations\n* For participants with histologically confirmed locally advanced or metastatic HCC:\n\n  * Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.\n  * Child-Pugh Score class A\n* Must have previously received SOC appropriate for their tumor type. Any number of prior therapies, including FGFR inhibitors, are permitted.\n* Agree to provide archival tumor tissue no older than 2 years from the time of enrollment, if available. If an archived specimen is not available, a biopsy is not required.\n\nPart B, Cohort 1:\n\n* Histologically confirmed locally advanced\u002Fmetastatic HCC who have previously received standard of care.\n* Barcelona Clinic Liver Cancer (BCLC) stage B that is not eligible for locoregional therapy, or stage C.\n* Child-Pugh Score class A\n* Availability of an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen obtained ≤2 years prior to screening for submission to sponsor-designated central laboratory for FGF19 IHC testing.\n* At least 1 measurable lesion by RECIST v1.1.\n\nPart B, Cohort 2:\n\n* Histologically confirmed advanced solid tumor except FGFR3-altered urothelial carcinoma and primary central nervous system tumors who have previously received standard of care. Note: Participants with confirmed diagnosis of locally advanced or metastatic HCC are not eligible for Cohort 2.\n* Must have an eligible activating gain-of-function alteration in the FGFR3 or FGFR4 gene, or focal amplifications of FGF19\n* Archival tumor tissue biopsy specimen no older than 2 years from the time of enrollment, if available. If a tissue biopsy specimen is not available, a biopsy is not required.\n* At least 1 measurable lesion by RECIST v1.1.\n\nKey Exclusion Criteria:\n\nAll Patients:\n\n* Have disease that is suitable for local therapy administered with curative intent.\n* Have not recovered from reversible toxicity of prior anticancer therapy to \\\u003C Grade 1 or baseline (except toxicities that are not clinically significant or not expected to resolve, including but not limited to, alopecia, fatigue, skin discoloration, or Grade 1 neuropathy).\n* Have received the following anticancer therapy:\n\n  1. Any immunotherapy or other antibody therapy within 28 days prior to the first dose of the study drug.\n  2. A TKI \\\u003C 5 days or 5X the terminal Phase elimination half-lives, whichever is longer, prior to the first dose of TYRA-430.\n  3. Other systemic therapy not listed above \\\u003C 14 days prior to the first dose of the study drug.\n* Participant discontinued a prior anti-FGFR therapy due to significant toxicity, defined as hepatotoxicity ≥ Grade 3 or any Grade 4 toxicity according to CTCAE v5.0.\n* Has a serum phosphorus level \\> upper limit of normal (ULN) during screening that remains \\>ULN despite medical management.\n* History of or current uncontrolled cardiovascular disease.\n* Active, symptomatic, or untreated brain metastases.\n* Have a diagnosis of primary CNS malignancies.\n* Gastrointestinal disorders that will affect oral administration or absorption of TYRA-430.\n* Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.\n* Any reason that, in the view of investigator, would substantially impair the ability of the participant to comply with study procedures and increase the risk to the participant.\n\nPart B, Cohort 1:\n\n* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.\n* Prior treatment with pan-FGFR inhibitors or FGFR4-selective inhibitors.\n\nPart B, Cohort 2:\n\n* Histologically confirmed locally advanced\u002Fmetastatic HCC.\n* Histologically confirmed urothelial cancer.",{"count":443,"type":21},100,[24],"A Phase 1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary antitumor activity of TYRA-430 in cancers with FGF\u002FFGFR pathway aberrations, including locally advanced\u002Fmetastatic hepatocellular carcinoma and other advanced solid tumors.",[69,447,448,449,450,451,452,453,454,455,456,457,458,459],"Solid Tumors","Solid Tumor, Adult","FGFR Gene Amplification","FGFR Gene Alterations","FGFR3 Gene Alteration","FGFR3 Gene Mutation","Advanced Solid Tumors","FGFR4 Gene Mutation","FGFR4 Gene Fusions","FGF19 Gene Amplification","FGF19 Gene Overexpression","FGFR3 Gene Fusions","Locally Advanced Unresectable Hepatocellular Carcinoma",[219,461,462,463,464,465,466,467,468,469,470,471,472],"metastatic cancer","solid tumors","FGF19 gene amplifications","FGFR4 gene alterations","FGFR3 gene alterations","FGF19 gene alterations","FGFR4 gene mutations","FGFR4 gene fusions","FGFR3 gene mutations","FGFR3 gene fusions","FGF19 gene overexpression","locally advanced unresectable cancer","2025-11-18",{"date":475,"type":132},"2025-11-20",{"date":477,"type":132},"2025-04-24",{"date":479,"type":21},"2028-09",{"name":481,"class":173},"Tyra Biosciences, Inc",16,{"id":484,"slug":485,"hasResults":11,"nctId":486,"briefTitle":487,"officialTitle":488,"acronym":4,"eligibilityCriteria":489,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":490,"targetDuration":4,"studyType":22,"phases":492,"briefSummary":494,"conditions":495,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":535,"lastUpdatePostDateStruct":536,"startDateStruct":538,"completionDateStruct":540,"leadSponsor":542,"locationsCount":544},"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":491,"type":21},28,[493],"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.",[496,497,498,499,500,501,502,503,504,505,506,507,508,509,510,511,67,69,512,513,514,515,516,517,518,519,520,521,522,523,524,525,526,527,528,529,530,531,97,532,101,533,105,534],"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 Gastric Carcinoma","Metastatic Malignant Digestive System Neoplasm","Metastatic Small Intestinal Carcinoma","Pancreatobiliary Carcinoma","Pathologic Stage IV Gastric Cancer AJCC v8","Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8","Pathologic Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8","Pathologic Stage IVB Esophageal Adenocarcinoma AJCC v8","Pathologic Stage IVB Esophageal Squamous Cell Carcinoma AJCC v8","Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IV Esophageal Squamous Cell Carcinoma AJCC v8","Postneoadjuvant Therapy Stage IV Gastric Cancer AJCC v8","Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8","Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Esophageal Adenocarcinoma AJCC v8","Postneoadjuvant Therapy Stage IVB Esophageal Squamous Cell Carcinoma AJCC V8","Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8","Stage IV Anal Cancer AJCC v8","Stage IV Colorectal Cancer AJCC v8","Stage IVA Colorectal Cancer AJCC v8","Stage IVB Colorectal Cancer AJCC v8","Stage IVC Colorectal Cancer AJCC v8","2025-09-30",{"date":537,"type":132},"2025-10-06",{"date":539,"type":132},"2020-08-07",{"date":541,"type":21},"2028-04-30",{"name":543,"class":139},"University of California, San Francisco",2,{"id":546,"slug":547,"hasResults":11,"nctId":548,"briefTitle":549,"officialTitle":550,"acronym":4,"eligibilityCriteria":551,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":552,"targetDuration":4,"studyType":22,"phases":554,"briefSummary":555,"conditions":556,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":557,"lastUpdatePostDateStruct":558,"startDateStruct":560,"completionDateStruct":562,"leadSponsor":564,"locationsCount":482},"100452181","phase-2-atezolizumab-in-combination-with-a-multi-kinase-inhibitor-for-the-treatment-of-unresectable-locally-advanced-or-metastatic-liver-cancer-100452181","NCT05168163","Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer","A Phase II Randomized Study of Atezolizumab Plus Multi-Kinase Inhibitor Versus Multi-Kinase Inhibitor Alone in Subjects With Unresectable, Advanced Hepatocellular Carcinoma Who Previously Received Atezolizumab Plus Bevacizumab","Inclusion Criteria:\n\n* Provide written informed consent =\\\u003C 28 days prior to randomization\n* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)\n\n  * NOTE: During the Active Monitoring Phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up\n* Age \\>= 18 years\n* Hepatocellular carcinoma (HCC) confirmed by histological\u002Fcytological diagnosis or clinically per the American Association for the Study of Liver Diseases (AASLD) or WASL 2018 criteria\n* Locally advanced, metastatic and\u002For unresectable disease that is not amendable to curative treatment\n* Previously progressed on atezolizumab in combination with bevacizumab as first line systemic therapy for advanced disease\n\n  * NOTE: 2nd line patients only\n* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1\n* Child Pugh class A\n* Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) serology tests.\n\n  * For subjects with active HBV, HBV deoxyribonucleic acid (DNA) \\\u003C 500 IU\u002FmL obtained ≤ =\\\u003C 28 days prior to randomization, and anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study\n* At least one measurable untreated malignant lesion per RECIST v1.1. Subjects who previously received local therapy (e.g., ablation, percutaneous ethanol injection, trans-arterial embolization\u002Fchemo-embolization) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1\n* Consent to using archival tumor tissues, if available\n\n  * NOTE: Non-availability of tumor tissue does not exclude the subject.\n* Willingness to provide mandatory blood specimens for correlative research\n* Willingness to provide mandatory tissue specimens for correlative research for the first 10 patients per arm (Mayo Clinic Rochester and Mayo Clinic Arizona ONLY)\n* Absolute neutrophil count (ANC) \\>= 1.5 x 10\\^9\u002FL (1500\u002FuL) without granulocyte colony-stimulating factor support (obtained =\\\u003C 28 days prior to randomization)\n* Lymphocyte count \\>= 0.5 x 10\\^9\u002FL (500\u002FuL) (obtained =\\\u003C 28 days prior to randomization)\n* Platelet count \\>= 75 x 10\\^9\u002FL (75,000\u002FuL) (obtained =\\\u003C 28 days prior to randomization)\n* Hemoglobin \\>= 90 g\u002FL (9 g\u002FdL) (obtained =\\\u003C 28 days prior to randomization)\n\n  * Subjects may be transfused to meet this criterion\n* Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =\\\u003C 5 x upper limit of normal (ULN) (obtained =\\\u003C 28 days prior to randomization)\n* Total bilirubin =\\\u003C 3 x ULN (obtained =\\\u003C 28 days prior to randomization)\n* Serum albumin \\>= 30 g\u002FL (3.0 g\u002FdL) (obtained =\\\u003C 28 days prior to randomization)\n* For subjects not receiving therapeutic anticoagulation: international normalized ratio (INR) or partial thromboplastin time (aPTT) =\\\u003C 1.5 × ULN (obtained =\\\u003C 28 days prior to randomization)\n* Serum creatinine =\\\u003C 2 x ULN or creatinine clearance \\>= 30 mL\u002Fmin (calculated using the Cockcroft-Gault formula) (obtained =\\\u003C 28 days prior to randomization)\n* Negative pregnancy test done =\\\u003C 14 days prior to randomization, for women of childbearing potential only\n\n  * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to grade =\\\u003C 1 prior to randomization, with the exception of alopecia and peripheral sensory neuropathy.\n* Subjects of childbearing potential agree to use two forms of medically approved contraception while taking the study drug and for at least 5 months after the last dose of atezolizumab or multi-kinase inhibitor. Subjects with partners of childbearing potential agree to use condoms, even after vasectomy, to avoid potential drug exposure to partner during study drug and for 5 months following the last dose of study drug\n* Ability to take oral medications\n\nExclusion Criteria:\n\n* Known diagnosis of fibrolamellar carcinoma, sarcomatoid carcinoma or mixed hepatocellular cholangiocarcinoma\n* Prior multi-kinase inhibitor treatment for advanced disease (e.g., cabozantinib, lenvatinib, sorafenib, regorafenib)\n\n  * NOTE: Use of multi-kinase inhibitor(s) for adjuvant or as part of loco-regional therapies is allowed as long as the therapy was completed \\>= 6 months prior to randomization\n* Any of the following prior therapies:\n\n  * Major surgery =\\\u003C 4 weeks prior to randomization; Minor surgery =\\\u003C 7 days prior to randomization (e.g., simple excision, tooth extraction, insertion of central lines\u002FMediport). Subjects with clinically relevant complications from prior surgery are not eligible\n  * Any anti-cancer agent =\\\u003C 2 weeks prior to randomization\n  * Radiation therapy =\\\u003C 4 weeks (1 week for palliative radiation for bone metastases and\u002For for pain control) or radionuclide treatment (e.g., I-131 or Y-90) =\\\u003C 6 weeks prior to randomization\n* Treatment with investigational therapy =\\\u003C 28 days prior to randomization\n* Known brain or leptomeningeal metastasis\n* Known co-infection of HBV and HCV. Subjects with a history of HCV infection but who are negative for HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR) will be considered non-infected with HCV\n* Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:\n\n  * Subjects with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study\n  * Subjects with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study\n  * Subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:\n\n    * Rash must cover \\\u003C 10% of body surface area\n    * Disease is well controlled at baseline and requires only low-potency topical corticosteroids\n    * No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months\n* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan\n\n  * NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the subject at high risk from treatment complication\n* Treatment with a live, attenuated vaccine =\\\u003C 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab treatment or =\\\u003C 5 months after the last dose of atezolizumab\n* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins\n* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation\n* Subjects with untreated or incompletely treated esophageal\u002Fgastric varices with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to local institutional standards) without any episodes of recurrent gastrointestinal bleeding requiring transfusion or hospitalization for \\> 28 days prior to randomization are eligible\n* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \\[IL-2\\]) =\\\u003C 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to randomization\n* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies\n\n  * Note: Prior treatment with atezolizumab is permitted\n* Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF alpha agents) =\\\u003C 2 weeks prior to randomization, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:\n\n  * Subjects who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study\n  * Subjects who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible\n* For subjects who are to receive cabozantinib: Treatment with strong inducers and\u002For strong inhibitors of CYP3A4 =\\\u003C 14 days prior to randomization, including rifampin (and its analogues) or St. John's wort. See https:\u002F\u002Fwww.fda.gov\u002Fdrugs\u002Fdrug-interactions-labeling\u002Fdrug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers for lists of known strong inhibitors and strong inducers of CYP3A4\n* Active tuberculosis\n* Other uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n  * Cardiovascular disorders including:\n\n    * Symptomatic congestive heart failure, unstable angina, or serious cardiac arrythmias\n    * Uncontrolled hypertensions defined as sustained blood pressure (BP) \\> 150 mmHg systolic BP, or \\> 100 mmHg diastolic BP despite optimal antihypertensive treatment\n    * Stroke (including transient ischemic attack), myocardial infarction, or other ischemic event =\\\u003C 3 months prior to randomization.\n    * Unstable arrythmia\n    * Thromboembolic event =\\\u003C 3 months prior to randomization. Subjects with thromboses of portal\u002Fhepatic vasculature attributed to underlying liver disease and\u002For liver tumor are eligible.\n  * Active bacterial infection requiring systemic treatment. Subjects on prophylactic antibiotics are eligible.\n  * Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS) related illness. Subjects with known HIV but without clinical evidence of an immunocompromised state and receiving anti-retroviral therapy are eligible\n  * Prior allogenic stem cell or solid organ transplantation\n  * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)\n\n    * Subjects with indwelling catheters (e.g., PleurX) are allowed.\n  * Uncontrolled or symptomatic hypercalcemia (ionized calcium \\> 1.5 mmol\u002FL, calcium \\> 12 mg\u002FdL or corrected serum calcium \\> ULN)\n  * Uncontrolled tumor-related pain\n\n    * Patients requiring pain medication must be on a stable regimen at the time of randomization\n    * Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.\n    * Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to randomization\n* Other malignancy(ies) =\\\u003C 5 years prior to randomization except adequately treated non-melanotic skin cancer, carcinoma-in-situ of the cervix, localized prostate cancer, ductal carcinoma in situ or stage I uterine cancer\n* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of study medication\n* Uncontrolled hepatic encephalopathy occurring =\\\u003C 6 weeks prior to randomization NOTE: Patients with =\\\u003C grade 2 encephalopathy =\\\u003C 6 weeks prior to randomization are eligible and supportive measures such as lactulose and antibiotics are allowed",{"count":553,"type":21},122,[25],"This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.",[50,69,80,84,88,97,101,105,114],"2025-09-10",{"date":559,"type":132},"2025-09-16",{"date":561,"type":132},"2022-05-27",{"date":563,"type":21},"2026-12-31",{"name":565,"class":139},"Academic and Community Cancer Research United"]