[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"locally-advanced-hepatocellular-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:locally-advanced-hepatocellular-carcinoma":50},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,7,0,[8,141,176,198,232,261,282],{"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":149,"enrollmentInfo":150,"targetDuration":4,"studyType":22,"phases":152,"briefSummary":153,"conditions":154,"keywords":161,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":166,"lastUpdatePostDateStruct":167,"startDateStruct":169,"completionDateStruct":171,"leadSponsor":173,"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.","18 Years","120 Years",{"count":151,"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.",[155,156,157,158,159,160,50,69,53,72],"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",[162,163,164,165],"PD-L1","PD-1","Tecentriq","Immunotherapy","2026-06-03",{"date":168,"type":132},"2026-06-04",{"date":170,"type":132},"2025-11-04",{"date":172,"type":21},"2028-01-31",{"name":174,"class":175},"National Cancer Institute (NCI)","NIH",{"id":177,"slug":178,"hasResults":11,"nctId":179,"briefTitle":180,"officialTitle":181,"acronym":4,"eligibilityCriteria":182,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":183,"targetDuration":4,"studyType":22,"phases":185,"briefSummary":186,"conditions":187,"keywords":4,"overallStatus":188,"whyStopped":4,"lastUpdateSubmitDate":189,"lastUpdatePostDateStruct":190,"startDateStruct":192,"completionDateStruct":194,"leadSponsor":196,"locationsCount":140},"100632270","phase-2-y-90-radioembolization-durvalumab-tremelimumab-and-zanzalintinib-for-the-treatment-of-unresectable-and-locally-advanced-hepatocellular-carcinoma-100632270","NCT07511504","Y-90 Radioembolization, Durvalumab, Tremelimumab, and Zanzalintinib for the Treatment of Unresectable and Locally-Advanced Hepatocellular Carcinoma","A Phase II Study to Evaluate the Efficacy and Safety of Y-90, Durvalumab, Tremelimumab, and Zanzalintinib in Patients With Unresectable and Locally-Advanced Hepatocellular Carcinoma","Inclusion Criteria:\n\n* Participant must provide written informed consent before any study-specific procedures or interventions are performed\n* Participants aged ≥ 18 years\n* Body weight \\> 30 kg\n* Patients must have radiologically, or histologically or cytologically confirmed hepatocellular cancer that is not amenable to transplant or resection:\n\n  * Barcelona Clinic Liver Cancer Stage B or C\n  * Cirrhosis grade of Child-Pugh (CP) A or CP-B7 (excluding albumin-bilirubin \\[ALBI\\] grade 3)\n  * Fibrolamellar and mixed hepatocellular\u002Fcholangiocarcinoma subtypes are not eligible\n* Disease must not be amenable to surgical resection, transplantation, or thermal ablation, or recurrent hepatocellular carcinoma (HCC) after a previous definitive therapy (surgery or thermoablative therapy)\n* Venous invasion (portal, hepatic, biliary) and infiltrative growth pattern are eligible\n* Eligible for Y-90 transarterial radioembolization (TARE) based on planning angiogram, with evidence of:\n\n  * ≥ 30% hepatic reserve (i.e., untreated background liver) AND\n  * Estimated lung exposure \\\u003C 30 Gy\u002F treatment (or 50 Gy cumulative total)\n* Patients with bi-lobar disease amenable to simultaneous or sequential TARE are eligible\n* Eastern Cooperative Oncology Group (ECOG) 0 - 1 at enrollment\n* Recovery to baseline or ≤ grade 1 (per Common Terminology Criteria for Adverse Events \\[CTCAE\\] version \\[v\\] 5.0) from toxicities related to any prior treatments, unless adverse events (AE\\[s\\]) are clinically non-significant and\u002For stable on supportive therapy\n* Hemoglobin ≥ 9 g\u002FdL (≥ 90 g\u002FL) (within 14 days before first dose of study treatment)\n* White blood cell count ≥ 2500\u002FμL (within 14 days before first dose of study treatment)\n* Absolute neutrophil count (ANC) ≥ 1.5 × 10\\^9\u002FL (1500\u002FμL), without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection (within 14 days before first dose of study treatment)\n* Platelet count ≥ 75 × 10\\^9\u002FL (≥ 75,000\u002FμL), without transfusion within 2 weeks of screening laboratory sample collection (within 14 days before first dose of study treatment)\n* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN) (within 14 days before first dose of study treatment)\n* Alkaline phosphatase (ALP) ≤ 5 x ULN (within 14 days before first dose of study treatment)\n* Total bilirubin ≤ 2 mg\u002FdL (≤ 34.2 μmol\u002FL) or \\\u003C 2 x ULN, whichever is higher (within 14 days before first dose of study treatment)\n* Serum albumin ≥ 2.8 g\u002FdL (within 14 days before first dose of study treatment)\n* International normalized ratio (INR) ≤ 1.7 x laboratory ULN (within 14 days before first dose of study treatment)\n* Stable renal function defined as serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCL) ≥ 40mL\u002Fmin (≥ 0.675mL\u002Fsec) using the Cockcroft-Gault equation (within 14 days before first dose of study treatment)\n* Urine protein\u002Fcreatinine ratio (UPCR) ≤ 1 mg\u002Fmg (≤ 113.2 mg\u002Fmmol), or 24-h urine protein ≤ 1 g (within 14 days before first dose of study treatment)\n* Has at least one measurable target lesion based on modified Response Evaluation Criteria in Solid Tumors (mRECIST)\n* Participants must have at least one lesion that is amendable to biopsy\n* Participant are asked to consent to tumor biopsies for biomarker analysis of the acquired tissue at the following timepoints: pre-treatment, on-treatment (i.e., after completing the initial combination cycle of durvalumab, tremelimumab and zanzalintinib), and at time of disease progression. These biopsies are optional and are not required for study participation\n* Sexually active fertile participants and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for:\n\n  * 96 days for sperm-producing participants or\n  * 186 days for participants of child-bearing potential (POCBP) after the last dose of zanzalintinib. Additionally, sperm-producing participants must agree not to donate sperm and POCBP must agree to not donate eggs (ova, oocyte) for the purpose of reproduction during these same periods\n* POCBP must not be pregnant at screening. POCBP participants are considered to be of childbearing potential unless one of the following criteria is met:\n\n  * Documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \\> 45 years-of-age in the absence of other biological or physiological causes.\n  * Participants \\\u003C 55 years-of-age must have a serum follicle stimulating (FSH) level \\> 40 mIU\u002FmL to confirm menopause).\n\n    * Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site\n\nExclusion Criteria:\n\n* Another primary tumor\n* Extrahepatic metastases\n* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.\n\n  * Note: Eligible participants must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.\n  * Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed\n* Prior systemic therapy for HCC\n* Prior Y-90 radioembolization\n\n  * Note: prior transarterial chemoembolization is permitted if \\> 6 months prior to enrollment\n* Advanced liver disease with a CP-B7 (ALBI grade 3), CP-B8, CP-B9 or CP- C, or active gastrointestinal bleeding or encephalopathy or refractory ascites\n* Radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible\n* Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA4 agent, or with an agent directed to another co-inhibitory T-cell receptor (e.g., TIGIT, LAG-3, TIM-3)\n* Prior treatment with zanzalintinib, cabozantinib, or similar class of multitargeted Tyrosine Kinase Inhibitor (mTKI)\n* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment\n* Participants cannot be on other forms of anti-cancer therapy at the same time, except as described within this protocol\n* Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitors (e.g., rivaroxaban), or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:\n\n  * Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low dose low molecular weight heparins (LMWH).\n  * Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.\n\n    * Note: participants must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer\n* Any complementary medications (e.g., herbal supplements or traditional medicines) to treat their HCC under study within 2 weeks before first dose of study treatment\n* Participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n  * Unstable of deteriorating cardiovascular disorders:\n\n    * Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes).\n    * Uncontrolled hypertension defined as sustained blood pressure (BP) \\> 140 mm Hg systolic or \\> 90 mm Hg diastolic despite optimal antihypertensive treatment.\n    * Stroke (including transient ischemic attack \\[TIA\\]), myocardial infarction (MI), or other clinically significant arterial thrombotic and\u002For ischemic event within 6 months before first dose of study treatment.\n    * Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before first dose of study treatment.\n\n      * Note: Participants with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.\n      * Note: Participants who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the Principal Investigator.\n    * Prior history of myocarditis\n* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\n\n  * Participant has evidence of tumor invading the GI tract,\n  * Active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis\n  * Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic\n  * Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.\n\n    * Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment.\n  * Known gastric or esophageal varices that are untreated or incompletely treated with bleeding or high risk for bleeding. Participants treated with adequate endoscopic therapy (according to institutional standards) without any episodes of recurrent GI bleeding requiring transfusion or hospitalization for at least 6 months prior to study entry are eligible.\n  * Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks\n* Clinically significant hematuria, hematemesis, or hemoptysis of \\> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before start of study intervention\n* Lesions invading a major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Participants with lesions invading the hepatic portal vasculature are eligible\n* Elevated lung shunting precluding safe treatment with Y-90 within acceptable thresholds of lung exposure, defined as \\> 30 Gy\u002Ftreatment or 50 Gy total for multiple treatments\n* Patients with future liver remnant volume \\\u003C 30% after Y-90 treatment\n* Patients in whom Y-90 is deemed unsafe due to risks of extra-pulmonary non-target embolization\n* Any deposition to the GI tract (per 99mTc-MAA SPECT-CT or Cone Beam CT)\n* Hepatic artery catheterization is contraindicated (e.g., vascular abnormalities or bleeding diathesis)\n* Severe liver dysfunction, including hepatic encephalopathy, clinically evident ascites or treatment with diuretics for ascites\n* Type Vp4 Portal vein tumor thrombosis (PVTT) involvement and lack of Tc-99m MAA deposition on the PVT per Tc-99m MAA SPECT\u002FCT\n* Participants with renal failure currently requiring dialysis of any kind are not eligible\n* Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation\n* Known allergy or hypersensitivity to any of the study drug or any of the study drug excipients\n* Other clinically significant disorders that would preclude safe study participation.\n\n  * Active infection requiring systemic treatment.\n\n    * Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.\n  * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness except for participants meeting all of the following criteria:\n\n    * On stable anti-retroviral therapy;\n    * CD4+ T cell count ≥ 200\u002FµL; and\n    * An undetectable viral load.\n\n      * Note: HIV testing is to be performed at screening if and as required by local regulation.\n      * Note: To be eligible, participants taking CYP inhibitors (e.g., zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose.\n      * Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider\n  * Uncontrolled hepatitis B Virus (HBV) infection. Participants with controlled hepatitis B virus (HBV), defined as receiving effective antiviral therapy and adequate viral suppression (i.e., HBV deoxyribonucleic acid \\[DNA\\] ≤ 2000 IU\u002FmL) are eligible.\n\n    * Note: participants must meet liver function inclusion parameters (i.e., ALT, AST, bilirubin)\n  * Hepatitis C (HCV) infection. Participants with active, controlled HCV infection are eligible provided liver function meets eligibility criteria and are receiving management of the disease per local institutional practice.\n  * Serious non-healing wound\u002Fulcer\u002Fbone fracture.\n\n    * Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.\n  * Malabsorption syndrome\n  * Pharmacologically uncompensated, symptomatic hypothyroidism.\n  * Requirement for hemodialysis or peritoneal dialysis.\n  * History of solid organ or allogenic stem cell transplant\n* Major surgery (e.g., GI surgery) within 8 weeks before first dose of study treatment. Minor surgeries (e.g., simple excision) within 5 days before first dose of study treatment. Participants must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Participant with clinically relevant ongoing complications from prior surgery are not eligible\n* Corrected QT interval calculated by the Fridericia formula (QTcF) \\> 470 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment. Participants with a history of additional risk factors for torsades de pointes (e.g., long QT syndrome) are also excluded \\[add reference for Fridericia formula\\].\n\n  * Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility\n* Any active, known or suspected autoimmune disease will be excluded, with the following exceptions:\n\n  * Type 1 diabetes mellitus.\n  * Hypothyroidism only requiring hormone replacement.\n  * Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment.\n  * Conditions not expected to recur in the absence of an external trigger\n* Known positive test for tuberculosis infection if supported by clinical or radiographic evidence of disease\n* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted\n* Free thyroxine outside the laboratory normal reference range. Asymptomatic participants with free thyroxine abnormalities are eligible per investigator's discretion\n* Any condition requiring systemic treatment with either corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Note the following exceptions:\n\n  * Inhaled, intranasal, intra-articular, or topical steroids are permitted.\n  * Adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.\n  * Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is permitted\n* Prior allogeneic stem cell or solid organ transplantation\n* Receipt of a live, attenuated vaccine within 30 days prior to enrollment\n* Documented hepatic encephalopathy within 6 months before first dose of study treatment\n* Clinically meaningful ascites (i.e., ascites requiring paracentesis or escalation in diuretics) within 6 months before first dose of study treatment\n* Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, safety of participation, or interpretation of results. This includes significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) or any other serious medical condition or abnormality in clinical laboratory tests that meet these criteria in the investigator's opinion\n* Patient is pregnant or lactating\n* Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube, or unwillingness or inability to receive IV administration\n* Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 2 years prior to first dose of study treatment that requires active treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6\n* History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent\n* Participants with any condition that, in the opinion of the investigator, could jeopardize the participant's safety or adherence to the study protocol",{"count":184,"type":21},40,[25],"This phase II trial tests how well giving Y-90 radioembolization, durvalumab, tremelimumab and zanzalintinib works for the treatment of hepatocellular carcinoma that cannot be removed by surgery (unresectable) and that has spread to nearby tissue or lymph nodes (locally advanced). Y-90 radioembolization is a therapy that injects radioactive particles directly into an artery that feeds liver tumors to cut off their blood supply. 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. Zanzalintinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving Y-90 radioembolization, durvalumab, tremelimumab and zanzalintinib may be effective for treating unresectable and locally-advanced hepatocellular carcinoma.",[50,80,97,114],"NOT_YET_RECRUITING","2026-03-30",{"date":191,"type":132},"2026-04-06",{"date":193,"type":21},"2026-04-02",{"date":195,"type":21},"2027-08-01",{"name":197,"class":139},"OHSU Knight Cancer Institute",{"id":199,"slug":200,"hasResults":11,"nctId":201,"briefTitle":202,"officialTitle":203,"acronym":4,"eligibilityCriteria":204,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":205,"targetDuration":4,"studyType":22,"phases":207,"briefSummary":208,"conditions":209,"keywords":219,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":224,"lastUpdatePostDateStruct":225,"startDateStruct":227,"completionDateStruct":229,"leadSponsor":231,"locationsCount":140},"100493464","phase-2-olanzapine-for-the-management-of-cancer-associated-appetite-loss-in-patients-with-advanced-esophagogastric-hepatopancreaticobiliary-colorectal-or-lung-cancer-100493464","NCT05705492","Olanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced Esophagogastric, Hepatopancreaticobiliary, Colorectal or Lung Cancer","ACTO: A Phase II, Randomized, Placebo-Controlled Study Evaluating Olanzapine in the Management of Cancer Cachexia","Inclusion Criteria:\n\n* Willingness to provide written informed consent\n* Individuals \\>= 18 years of age\n* Histologically confirmed advanced local or metastatic esophogastric, hepatopancreaticobiliary, colorectal, or lung cancer diagnosis within 12 weeks of screening\n* Patients with weight loss as defined by international consensus criteria (documented or patient-reported):\n\n  * ≥ 5% weight loss over the past 6 months\n  * ≥ 2% weight loss with body mass index (BMI) \\\u003C20 kg\u002Fm\\^2 or sarcopenia\n* Planned or ongoing first-line palliative antineoplastic therapy (cytotoxic chemotherapy, targeted therapy, immunotherapy, combinations) with or without radiation therapy and have not started the second cycle of first-line palliative antineoplastic therapy. Patients may have received adjuvant antineoplastic therapy at least 6 months prior to screening\n* Able to ambulate independently with or without assistive devices (e.g., cane, walker)\n* In the case of brain metastases, the individual must be asymptomatic or previously treated with a full cycle of therapy with recovery from any acute effects of radiation therapy or surgery before screening. Such individuals must have discontinued corticosteroid treatment and be neurologically stable for at least 4 weeks before screening\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n* Able and willing to discontinue the use of any drug or over-the-counter (OTC) product that may interact with the study drug (within a period sufficient for wash-out per the principal investigators \\[PI's\\] discretion) and thereafter while on the study\n* Willingness to comply with restrictions on chest\u002Fbreastfeeding\n* Individuals capable of childbearing and contributing viable sperm must be willing to comply with contraception requirements and not donate ova or sperm while on the study and for 1 month after that\n* A negative pregnancy test at baseline (BL) must be obtained for individuals capable of childbearing\n\nExclusion Criteria:\n\n* Plan for, or history of (within 30 days of enrollment), the use of an antipsychotic drug, including, but not limited to, risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone. This limitation does not include prochlorperazine and other phenothiazines as antiemetic therapy. The use of antipsychotics concurrent with protocol therapy will not be allowed\n* Current use of medications or supplements with the goal of enhancing appetite within ≥14 days, including:\n\n  * megestrol acetate\n  * cannabinoids (including, but not limited to dronabinol, medical cannabis, over the counter \\[OTC\\] cannabinoid products), and\u002For\n  * Corticosteroids (defined as ≥ 5mg of prednisone \\[or equivalent per day\\]), except for standard-of-care chemotherapy-induced nausea and vomiting prophylaxis\n* Known history of poorly controlled diabetes, defined as fasting morning blood sugars ≥300 mg\u002FdL or recent hemoglobin A1≥ 8. Individuals with diabetes will undergo hemoglobin A1c (HbA1c) blood testing if they do not have HbA1c results 12 weeks prior to enrollment\n* Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days before signing consent:\n\n  * Total bilirubin ≥5x upper limit of normal (ULN), aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SPGT\\]) ≥5X ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma, or hepatic metastases)\n  * Primary investigator (PI) discretion will determine continued eligibility after randomization occurs in the event the liver function test results are above the proposed ULN\n  * Renal disease requiring dialysis or calculated glomerular filtration rate (GFR) ≤ 30 mL\u002Fminute\u002F1.73 m\\^2 as calculated by the modification of diet in renal disease (MDRD) equation\n* Tube feeding or parenteral nutrition at the time of screening\n* Any condition that may negatively impact oral absorption of the study drug (including, but not limited to dysphagia, mucositis, gastrectomy, colitis, bowel obstruction, high output ileostomy) or any plan to undergo an intervention that will render such a condition\n* Recurrent ascites unresponsive to medical interventions and requires therapeutic paracentesis\n* Uncontrolled symptoms at randomization make the individual unsuitable for the study in the judgment of the PI. If uncontrolled symptoms can be effectively palliated for ≥1 week prior, enrollment may be considered at the discretion of the PI\n* Uncontrolled infection, including coronavirus disease 2019 (COVID-19), at time of randomization. Individuals with the uncontrolled infection will not be eligible as the symptomology of infection may obscure the outcomes of this study\n* Other medical or psychiatric condition, including recent (within 1 year) or active suicidal ideation\u002Fbehavior or laboratory abnormality, may increase the risk of study participation or, in the PI's judgment, makes the participant inappropriate for the study",{"count":206,"type":21},66,[25],"This phase II trial tests how well olanzapine works in managing cancer cachexia in patients experiencing esophagogastric, hepatopancreaticobiliary, colorectal, or lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) -associated appetite loss while receiving non-curative cancer therapy. Loss of appetite (\"anorexia\") in the setting of cancer is a key feature of \"cachexia,\" a syndrome associated with loss of weight and muscle as well as weakness and fatigue. Olanzapine is a drug that targets key neurotransmitters (a type of molecule in the central nervous system that transmits messages to the rest of the body) that may stimulate appetite, restore caloric intake, minimize weight loss, and improve quality of life (QOL).",[210,211,212,213,214,215,216,217,218,50],"Advanced Malignant Solid Neoplasm","Advanced Biliary Tract Carcinoma","Advanced Esophageal Carcinoma","Metastatic Esophageal Carcinoma","Locally Advanced Colorectal Carcinoma","Locally Advanced Esophageal Carcinoma","Locally Advanced Gastric Carcinoma","Metastatic Colorectal Carcinoma (mCRC)","Advanced Lung Carcinoma",[220,221,222,223],"cancer","cachexia","weight loss","loss of appetite","2026-01-19",{"date":226,"type":132},"2026-01-21",{"date":228,"type":132},"2024-07-17",{"date":230,"type":21},"2026-12-31",{"name":197,"class":139},{"id":233,"slug":234,"hasResults":11,"nctId":235,"briefTitle":236,"officialTitle":237,"acronym":238,"eligibilityCriteria":239,"healthyVolunteers":11,"sex":17,"minAge":240,"maxAge":241,"enrollmentInfo":242,"targetDuration":4,"studyType":22,"phases":244,"briefSummary":245,"conditions":246,"keywords":247,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":252,"lastUpdatePostDateStruct":253,"startDateStruct":255,"completionDateStruct":257,"leadSponsor":258,"locationsCount":260},"100468227","phase-2-multinational-phase-ii-trial-to-compare-safety-and-efficacy-of-sirt-y-90-resin-microspheres-followed-by-atezolizumab-plus-bevacizumab-vs-sirt-sirt-y90-followed-by-placebo-in-locally-advanced-hcc-patients-100468227","NCT05377034","Multinational Phase II Trial to Compare Safety and Efficacy of SIRT (Y-90 Resin Microspheres) Followed by Atezolizumab Plus Bevacizumab, vs SIRT (SIRT-Y90) Followed by Placebo in Locally Advanced HCC Patients","A Multinational, Double-blind, Placebo-Controlled, Parallel Randomized Arms, Phase II Trial to Compare Safety and Efficacy of Selective Internal Radiation Therapy (Y-90 Resin Microspheres) Followed by Atezolizumab Plus Bevacizumab) Versus Selective Internal Radiation Therapy (SIRT-Y90) Followed by Placebo in Patients With Locally Advanced Hepatocellular Carcinoma (HCC)","STRATUM","Inclusion Criteria:\n\nPatients must fulfill all of the following criteria to be eligible for this study:\n\n1. Unequivocal diagnosis of HCC (AASLD 2010 diagnostic criteria or histology) that is locally advanced without extra-hepatic metastases but with significant tumor burden, i.e.,\n\n   * Tumor confined to the liver that is beyond the up-to-7 criteria, and\u002For\n   * Tumor with vascular invasion VP 1-3 and\u002For Vv 1-2 (at the discretion of site investigator) Both local and central assessments are required at screening, prior to any study treatment. Sites are required to send all CT\u002FMRI images for central imaging review. The central assessment result will be made known to sites and will take precedence in determining a patient's study eligibility in case of a discrepancy between local and central review.\n2. Aged 21 years old and above of either gender.\n3. Patient eligible for SIRT-Y90 treatment after assessment with macro-aggregated albumin labeled with technetium-99 (Tc-99m MAA) scan on SPECT\u002FCT or planar imaging with all of the following criteria prior to each SIRT-Y90 treatment:\n\n   * Lung shunting \\\u003C20% on SPECT\u002FCT or planar imaging\n   * Lung dose limit of \\\u003C25Gy for single treatment or \\\u003C30Gy for cumulative treatment (second delivery within 4-6 weeks)\n4. No prior radiation to the liver.\n5. No prior systemic adjuvant or neoadjuvant therapy for HCC.\n6. Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan or MRI.\n7. Negative HIV test at screening, with the following exception - patients with a positive HIV test at screening are eligible provided they fulfil all of the following criteria:\n\n   * Are stable on anti-retroviral therapy\n   * Have a CD4 count ≥ 200\u002FμL\n   * Have an undetectable viral load\n8. Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) tests.\n9. Patients with active HBV: HBV DNA \\\u003C3000 IU\u002FmL, initiation of anti-HBV treatment at least 14 days prior to randomization, and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., entecavir).\n\n   For patients with HBV DNA ≥ 500 IU\u002FmL during screening, anti-HBV treatment will be initiated and HBV DNA levels will be re-assessed prior to randomization.\n10. ECOG performance status 0 - 1.\n11. Child-Pugh A (up to 6 points).\n12. Adequate hematological, renal, and hepatic function as follows:\n\n    * Lymphocyte count ≥ 0.5 x 10\\*\\*9\u002FL (500\u002FμL)\n    * Platelets ≥75,000\u002FμL without transfusion\n    * Hemoglobin \\>9.5 g\u002FdL (Patients may be transfused to meet this criterion.)\n    * Serum bilirubin ≤ 3 x ULN\n    * For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 2.0 x ULN\n    * ALP ≤5×institutional upper limit of normal\n    * AST and ALT ≤5×institutional upper limit of normal\n    * Albumin ≥2.8 g\u002FdL\n    * Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL\u002Fmin (calculated using the Cockcroft-Gault formula)\n    * Absolute Neutrophil Count ≥1.5×10\\*\\*9\u002FL without granulocyte colony-stimulating factor support\n    * Urine dipstick for proteinuria \\\u003C2+ at screening\n\n      * Patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \\\u003C1g of protein in 24 hours\n13. Life expectancy of at least 3 months without any active treatment.\n14. Suitable for protocol treatment as determined by clinical assessment undertaken by the site investigator.\n15. Performance of an esophagogastroduodenoscopy (EGD) within 6 months prior to randomization as part of pre-procedure work-up or during screening, and assessment and complete treatment of varices of all sizes per local standard of care prior to randomization.\n\n    Patients with varices should be re-assessed prior to randomization to ensure complete treatment of varices of all sizes per local standard of care.\n16. Willing, able and mentally competent to provide written informed consent prior to any testing undertaken for this study protocol, including screening tests and evaluations that are not considered to be part of the patient's routine care.\n17. Female patients must be either postmenopausal or, if premenopausal, must have a negative pregnancy test and agree to use two forms of contraception if sexually active during the treatment period, for at least 5 months after the last dose of atezolizumab and 6 months after the last dose of bevacizumab.\n18. Male patients must be surgically sterile, or if sexually active and having a pre-menopausal female partner, they must be using an acceptable form of contraception during the treatment period and for 6 months after the last dose of bevacizumab.\n\nExclusion Criteria:\n\nThe following criteria should be checked. If ANY apply, the patient must not be included in the study:\n\n1. Patient not eligible for SIRT-Y90 treatment after assessment with macro-aggregated albumin labeled with technetium-99 (MAA) scan on SPECT\u002FCT or planar imaging.\n2. Patients who have SAE \\> grade 3 within 4 weeks after receiving SIRT-Y90. For patients who experience SAE \\> grade 3 after receiving SIRT-Y90 (1st or 2nd administration), the duration between the SIRT-Y90 dose and randomization and\u002For 1st and 2nd SIRT-Y90 dose (for two-staged delivery) may be extended by an additional 4 weeks to re-assess the patient's eligibility.\n3. Patients who have had \\>2 administrations of hepatic artery directed therapy.\n4. Patients who have had hepatic artery directed therapy done \\\u003C4 weeks prior to date of ICF signing.\n5. Patients who have had systemic adjuvant or neoadjuvant therapy for HCC.\n6. Prior hepatic radiation therapy for HCC or other malignancy.\n7. Patient who has received any immunotherapy (including interferon-alfa, peginterferon alfa-2a, peginterferon alfa-2b, thymosin-α1, etc.) within 30 days prior to randomization, is currently receiving immunotherapy or is planned to start immunotherapy during the study (e.g., for the management of active CHB or CHC according to local guidelines).\n8. Has evidence that \\\u003C30% of the total liver volume is disease-free.\n9. Currently receiving any other investigational agents for the treatment of their cancer.\n10. Has intractable clinical ascites (in spite of optimal diuretic treatment) or any other clinical signs of liver failure, on physical examination.\n11. Untreated or incompletely treated esophageal and\u002For gastric varices prior to randomization.\n12. Presence of tumor thrombus in the main trunk of the portal vein or a portal vein branch contralateral to the primarily involved lobe (or both) i.e. beyond VP3 and\u002For tumor thrombus in the inferior vena cava or right atrium i.e. beyond Vv2.\n13. Any metastatic disease i.e. lymph node ≥15 mm in short axis or distant metastasis.\n14. Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least five years.\n15. Presence of clinical signs of CNS metastases due to their poor prognosis and because progressive neurologic dysfunction would confound the evaluation of neurologic and other adverse events.\n16. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection (except viral hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n17. Inadequately controlled arterial hypertension (defined as systolic blood pressure \\[BP\\]\\>150 mmHg and\u002For diastolic BP \\>100 mmHg), based on an average of at least three BP readings on separate occasions.\n\n    • Anti-hypertensive therapy to achieve these parameters is allowed.\n18. Any of the following contraindications to angiography and selective visceral catheterization:\n\n    * Bleeding diathesis, not correctable by the standard forms of therapy.\n    * Severe peripheral vascular disease that would preclude arterial catheterization.\n19. Significant cardiovascular disease (such as cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to randomization), unstable arrhythmia, or unstable angina.\n20. History of congenital long QT syndrome or corrected QT interval \\> 500 ms (calculated with use of the Fridericia method) at screening\n21. History of uncorrectable electrolyte disorder affecting serum levels of potassium, calcium, or magnesium\n22. Current or recent use (within 10 days prior to angiogram) of aspirin (\\>325 mg\u002Fday) or current or recent treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol.\n\n    • Use of dipyridamole, ticlopidine, clopidogrel, and cilostazol is allowed for patients who do not have any active bleeding for the past 6 months after review with attending physician.\n23. Current or recent (within 10 days prior to angiogram) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose.\n\n    * Prophylactic anticoagulation for the patency of venous access devices is allowed provided the activity of the agent results in an INR \\\u003C1.5×ULN and aPTT is within normal limits (according to institutional standards) within 14 days prior to Day 1 of Cycle 1.\n    * Prophylactic use of low-molecular-weight heparin (i.e., enoxaparin 40 mg\u002Fday) is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa®) and rivaroxaban (Xarelto®) is not recommended due to bleeding risk.\n24. History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIRT-Y90 or atezolizumab or bevacizumab.\n25. The patient has active or history of autoimmune disease or immune deficiency such as, but not limited to, multiple sclerosis, systemic lupus erythematosus, and inflammatory bowel disease, with the following exceptions:\n\n    * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.\n    * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.\n    * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of 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 prior to screening.\n26. The patient requires concomitant treatment with any immunosuppressive or immunostimulant agent, or with systemic corticosteroids prescribed for chronic treatment (more than 7 consecutive days).\n27. Inability or unwillingness to understand or sign a written informed consent document.\n28. Female patients who are pregnant or currently breastfeeding.\n29. Current enrolment in any other investigational therapeutic drug or device study.","21 Years","99 Years",{"count":243,"type":21},100,[25],"This is a multi-national, phase II, parallel-arm, double-blind, placebo-controlled, two-arm study designed to assess the efficacy and safety of SIRT-Y90 followed by atezolizumab plus bevacizumab \\[study arm\\], versus SIRT-Y90 followed by placebo \\[control arm\\] in patients with locally advanced Hepatocellular Carcinoma (HCC).",[50],[248,249,250,251],"SIRT-Y90","Atezolizumab plus Bevacizumab","Hepatocellular Carcinoma","SIR-Sphere","2025-09-30",{"date":254,"type":132},"2025-10-06",{"date":256,"type":132},"2022-10-26",{"date":172,"type":21},{"name":259,"class":139},"National Cancer Centre, Singapore",14,{"id":262,"slug":263,"hasResults":11,"nctId":264,"briefTitle":265,"officialTitle":266,"acronym":4,"eligibilityCriteria":267,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":268,"targetDuration":4,"studyType":22,"phases":270,"briefSummary":271,"conditions":272,"keywords":4,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":273,"lastUpdatePostDateStruct":274,"startDateStruct":276,"completionDateStruct":278,"leadSponsor":279,"locationsCount":281},"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":269,"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":275,"type":132},"2025-09-16",{"date":277,"type":132},"2022-05-27",{"date":230,"type":21},{"name":280,"class":139},"Academic and Community Cancer Research United",16,{"id":283,"slug":284,"hasResults":11,"nctId":285,"briefTitle":286,"officialTitle":286,"acronym":287,"eligibilityCriteria":288,"healthyVolunteers":11,"sex":17,"minAge":148,"maxAge":4,"enrollmentInfo":289,"targetDuration":4,"studyType":290,"phases":4,"briefSummary":291,"conditions":292,"keywords":295,"overallStatus":128,"whyStopped":4,"lastUpdateSubmitDate":298,"lastUpdatePostDateStruct":299,"startDateStruct":301,"completionDateStruct":303,"leadSponsor":305,"locationsCount":140},"100583203","holmium-166-transarterial-radioembolization-for-the-treatment-of-hepatocellular-carcinoma-100583203","NCT06873269","Holmium-166 Transarterial Radioembolization for the Treatment of Hepatocellular Carcinoma","TARE for HCC","Inclusion Criteria:\n\n* aged 18 year or older\n* diagnosed with locally advanced HCC without extra-hepatic metastases\n* HCC must not be amendable to treatment by surgical resection or percutaneous radiofrequency ablation\n* after assessment by the investigator and multidisciplinary tumor board, the patient is considered suitable for protocol treatment with Holmium-166 TARE\n* ECOG performance status 0-2\n* child-Pugh A-B\n* tumor response evaluable with mRECIST criteria during follow-up\n\nExclusion Criteria:\n\n* prior treatment with any of the following treatment modalities for HCC: systemic therapy, hepatic radiation therapy\n* currently enrolled in clinical studies where patient receive investigational therapeutic drug\n* metastatic disease\n* concurrent malignancy\n* active contra-indications to angiography or selective catherization (i.e. severe vascular disease or bleeding diathesis)\n* uncontrolled and\u002For severe comorbidities (active infection, heart failure,...) with limited estimated life expectancy\n* history of or know allergic reactions to used compounds",{"count":243,"type":21},"OBSERVATIONAL","This study aims to evaluate the effectiveness and safety of Holmium-166 (Ho-166) transarterial radioembolization (TARE) for treating patients with locally advanced hepatocellular carcinoma (HCC), a common type of liver cancer. HCC is often linked to conditions like liver cirrhosis and viral hepatitis, with a poor prognosis for advanced stages. TARE involves delivering radioactive particles directly to liver tumors, sparing healthy tissue and providing targeted radiation.\n\nThis study will include patients diagnosed with HCC who have received Holmium-166 TARE treatment between January 2010 and December 2024. Researchers will look at patient and tumor characteristics, side effects, how well the treatment works, and survival outcomes. The goal is to determine whether Holmium-166 TARE is a safe and effective treatment option for people with locally advanced HCC.\n\nThe findings will help doctors better understand how this therapy can be used to treat liver cancer and whether it can improve survival rates for patients with this challenging disease.",[50,293,294],"Liver Cirrhosis","Non-metastatic Hepatocellular Carcinoma",[296,297],"holmium-166","transarterial radioembolization","2025-03-06",{"date":300,"type":132},"2025-03-12",{"date":302,"type":132},"2025-02-01",{"date":304,"type":21},"2026-02-01",{"name":306,"class":139},"Universitair Ziekenhuis Brussel"]