[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"stage-iii-hepatocellular-carcinoma-ajcc-v8\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:stage-iii-hepatocellular-carcinoma-ajcc-v8":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,13,0,[8,44,66,186,216,241,264,287,307,330,351,419,442],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100596243","phase-1-zanzalintinib-in-second-line-and-beyond-for-the-treatment-of-advanced-liver-cancer-100596243",false,"NCT07042919","Zanzalintinib in Second Line and Beyond for the Treatment of Advanced Liver Cancer","A Phase Ib\u002FII Study of Zanzalintinib in Second Line and Beyond for the Treatment of Advanced Hepatocellular Carcinoma","Inclusion Criteria:\n\n* 3.1.1 Patients with confirmed diagnosed HCC who are not amendable to curative treatments.\n* 3.1.2 Patients must have documented objective radiographic progression during or after treatment with any first or second line therapy, or intolerance to any first or second line therapy, which include immunotherapy-based combination, or non-immunotherapy-based treatment, except cabozantinib.\n* 3.1.3 Patients must have a Child-Pugh class A or Child-Pugh class B (B7 or B8) score for cirrhosis mortality. Child-Pugh class B, B9 is excluded. See Appendix A for Child-Pugh Class Scores.\n* 3.1.4 Patients must have measurable disease according to RECIST v1.1. See Section 7 for the evaluation of measurable disease. See Appendix B for RECIST v1.1 criteria.\n* 3.1.5 Patients may have had up to two prior lines therapy (not including cabozantinib) in the advanced metastatic setting. Palliative radiation or locoregional therapies are not considered a line of therapy.\n* 3.1.6 Patients must be age ≥ 18 years.\n* 3.1.7 Patients must exhibit a\u002Fan ECOG Status of 0-1 Refer to Appendix C; (Karnofsky ≥ 60%. See Appendix D.)\n* 3.1.8 Patients must have adequate organ and bone marrow function as defined below in Table 2 (Child-Pugh Class A): Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL, Hemoglobin (Hgb) ≥ 9 g\u002FdL, Platelets (PLT) ≥ 75,000\u002FmcL, International Normalized Ratio (INR) ≤ 1.7 x upper limit of normal (ULN), activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN), Total bilirubin ≤ 3.0 mg\u002Fdl, Albumin ≥ 2.5 (g\u002FdL), AST (SGOT) ≤ 5 x institutional ULN, ALT (SGPT) ≤ 5 x institutional ULN, ALP ≤ 5.0 x institutional ULN, Creatinine Clearance \\> 40 mL\u002F minute if serum creatinine is elevated above 1.5 X ULN, Urine protein-to-creatinine ratio (UPCR) ≤ 1.5 mg\u002Fmg (≤ 169.8 mg\u002Fmmol) creatinine.\n* 3.1.8 Patients must have adequate organ and bone marrow function as defined below in Table 2 (Child-Pugh Class B): Absolute neutrophil count (ANC) ≥ 1,200\u002FmcL, Hemoglobin (Hgb) ≥ 8.5 g\u002FdL, Platelets (PLT) ≥ 60,000\u002FmcL, International Normalized Ratio (INR) ≤ 2.3 x upper limit of normal (ULN), activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN), Total bilirubin ≤ 3.0 mg\u002Fdl, Albumin ≥ 2.5 (g\u002FdL), AST (SGOT) ≤ 5 x institutional ULN, ALT (SGPT) ≤ 5 x institutional ULN, ALP ≤ 5.0 x institutional ULN, Creatinine Clearance \\> 40 mL\u002F minute if serum creatinine is elevated above 1.5 X ULN, Urine protein-to-creatinine ratio (UPCR) ≤ 1.5 mg\u002Fmg (≤ 169.8 mg\u002Fmmol) creatinine.\n* 3.1.9 POCBP and any of their partners with sperm-producing reproductive capability must agree to use a highly effective method of contraception (defined in Appendix E) throughout the course of the study and for 186 days after the last dose of treatment. Additional contraceptive method, such as a barrier method (e.g., condom) is also required.\n* 3.1.10 Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence), refer to Appendix E, with partners of childbearing potential from time of informed consent, for the duration of study participation, and for 96 days following completion of therapy.\n* 3.1.11 POCBP must agree to use a highly effective method of contraception (defined in Appendix E) throughout the course of the study and for 186 days after the last dose of treatment. Additional contraceptive method, such as a barrier method (e.g., condom) is also required.\n* 3.1.12 Patients must have the ability to understand and the willingness to sign a written informed consent document and comply with the study requirements.\n* 3.1.13 Patients must have the ability to swallow, retain, and absorb oral medications or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.\n\nExclusion Criteria:\n\n* 3.2.1 Patients with prior treatment with zanzalintinib.\n* 3.2.2 Patients who have received any type of small-molecule kinase inhibitor (including an investigational kinase inhibitor) within 14 days prior to study Day 1 treatment.\n* 3.2.3 Patients who have received ≥ 3 prior therapies in the advanced setting.\n* 3.2.4 Patients with prior Cabozantinib use.\n* 3.2.5 Patients who have had chemotherapy, cytotoxic, biologic, radiation, or other systemic anticancer (including investigational) therapy within 4 weeks prior to study Day 1 treatment.\n* 3.2.6 Patients who have received palliative radiation therapy for bone metastasis within 14 days or any other radiation therapy within 4 weeks days before first dose of study treatment.\n* 3.2.7 Patients who have undergone systemic treatment with radionuclides within 6 weeks (42 days) before first dose of study treatment.\n* 3.2.8 Patients who have received any local anticancer therapy including surgery, PEI, RFA, MWA, transarterial chemoembolization (TACE), or trans arterial radioembolization (TARE) within 28 days prior to first dose of study treatment.\n* 3.2.9 Patients with any unresolved toxicity NCI Common Terminology Criteria for Adverse Event (CTCAE 5.0) Grade \\>1 at baseline, including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and\u002For stable on supportive therapy (eg, physiological replacement of corticosteroid, from a previous anticancer therapy, with the following exceptions: Alopecia, vitiligo, and the laboratory values defined in the inclusion criteria., Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the treating physician., Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with zanzalintinib may be included only after consultation with the principal investigator.\n* 3.2.10 Patients with a known prior or concurrent malignancy that is progressing or requires active treatment within 2 years of first dose of study treatment. Note: The following exceptions may be made: 1)For patients with malignancies like basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer; or superficial skin cancers, localized low-grade tumors deemed cured and not treated with systemic therapy, and incidentally diagnosed prostate cancer if assessed as stage\n* 3.2.11 Patients with known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and\u002For surgery (including radiosurgery) and stable for at least 28 days prior to first dose of study treatment. Note: Patients with an incidental finding of an isolated brain lesion \\\u003C 1 cm in diameter may be eligible after Principal Investigator approval if the lesion is radiographically stable for 28 days before first dose and does not require treatment per Investigator judgement. Note: Eligible patients must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed\n* 3.2.12 Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to zanzalintinib.\n* 3.2.13 Patients who are on concomitant anticoagulation therapy with oral anticoagulants (e.g., warfarin or direct thrombin inhibitors) and platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following: a. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). b. Therapeutic doses of LMWH or anticoagulation with direct Factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in patients 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. Note: Patients must have discontinued oral anticoagulants within 3 days or 5 halflives prior to first dose of study treatment, whichever is longer.\n* 3.2.14 Patients who are taking any complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease under study with in 2 weeks prior to cycle 1 day 1. Note: Taking complementary medications to treat symptoms of the cancer is allowed.\n* 3.2.15 Patient has uncontrolled, significant intercurrent or recent illness.\n* 3.2.16 Patients with 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 84 days prior to registration.\n* 3.2.17 Patients with symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed).\n* 3.2.18 Patients with lesions invading major blood vessel including but not limited to inferior vena cava, pulmonary artery, or aorta. Note: Patients with intravascular tumor extension (e.g., tumor thrombus in renal vein or inferior vena cava) may be eligible following PI approval. Patients with lesions invading the hepatic portal vasculature are eligible\n* 3.2.19 Patients with other clinically significant disorders that would preclude safe study participation\n* 3.2.20 Patients with Recent surgery within the following parameters: • Major surgery (e.g., GI surgery or removal\u002Fbiopsy of brain metastasis) within 8 weeks before first dose of study treatment. • Prior laparoscopic surgeries (i.e. nephrectomy) within 28 days prior to first dose of study treatment. Minor surgery (e.g., simple excision, tooth extraction) within 5 days before first dose of study treatment. • Complete wound healing from major surgery and from minor surgery (e.g., simple excision, tooth extraction) must have occurred at least prior to first dose of study treatment. • Patients with clinically relevant ongoing complications from prior surgery are not eligible. • Minor surgery (e.g., simple excision, tooth extraction) within 5 days prior to first dose of study treatment. Note: if a patient has had a recent surgery outside of the proscribed interval, complete wound healing from said surgery must have occurred prior to first dose of study treatment. Note: Fresh tumor biopsies should be performed at least 5 days prior to registration. Patients with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.\n* 3.2.21 Patients with corrected QT interval calculated by the Fridericia formula (QTcF) \\>480 ms within 14 days per electrocardiogram (ECG) prior to first dose of study treatment. Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.\n* 3.2.22 Patients who are pregnant (positive serum or urine test within 72 hours prior to enrollment) or nursing. Pregnant people are excluded from this study because zanzalintinib is a next-generation TKI with potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the nursing parent with zanzalintinib , breastfeeding should be discontinued if the nursing parent is treated with zanzalintinib. POCBP are considered to be of childbearing potential unless one of the following criteria is met: 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. In addition, POCBP \\\u003C 55 years-of-age must have a serum follicle stimulating hormone \\[FSH\\] level \\> 40 mIU\u002FmL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. Note: If a urine pregnancy test is positive or cannot be confirmed negative, a serum pregnancy test will be required.\n* 3.2.23 Patients with psychiatric illness\u002Fsocial situations that would limit compliance with study requirements or give informed consent, per the opinion of the treating investigator.\n* 3.2.24 Patients with other conditions which, in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study.\n* 3.2.25 Patients with documented hepatic encephalopathy (HE) within 6 weeks before first dose of study treatment. Patients with clinically meaningful ascites (i.e., ascites requiring paracentesis or escalation in diuretics) within 2 weeks prior to registration, C1D1.","ALL","18 Years",{"count":19,"type":20},59,"ESTIMATED","INTERVENTIONAL",[23,24],"PHASE1","PHASE2","This phase Ib\u002FII trial tests the safety, side effects, and best dose of zanzalintinib and how well it works in treating patients with hepatocellular (liver) cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Zanzalintinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply, which may help keep tumor cells from growing. Giving zanzalintinib may be safe, tolerable, and\u002For effective in treating patients with advanced liver cancer.",[27,28,29,30],"Advanced Hepatocellular Carcinoma","Cirrhosis","Stage III Hepatocellular Carcinoma AJCC v8","Stage IV Hepatocellular Carcinoma AJCC v8","RECRUITING","2026-06-23",{"date":34,"type":35},"2026-06-25","ACTUAL",{"date":37,"type":35},"2026-03-30",{"date":39,"type":20},"2031-03-04",{"name":41,"class":42},"Devalingam Mahalingam","OTHER",1,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":4,"eligibilityCriteria":50,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":51,"targetDuration":4,"studyType":21,"phases":53,"briefSummary":55,"conditions":56,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":57,"lastUpdatePostDateStruct":58,"startDateStruct":59,"completionDateStruct":61,"leadSponsor":63,"locationsCount":65},"100605737","phase-3-testing-immunotherapy-with-or-without-stereotactic-body-radiation-therapy-in-patients-with-advanced-liver-cancer-helio-rt-trial-100605737","NCT07166406","Testing Immunotherapy With or Without Stereotactic Body Radiation Therapy in Patients With Advanced Liver Cancer, HELIO-RT Trial","Phase III Randomized Trial of IO-Based Systemic Treatment +\u002F- Liver SBRT in Hepatocellular Cancer With Macrovascular Invasion (HELIO-RT)","Inclusion Criteria:\n\n* PRIOR TO STEP 1 REGISTRATION:\n* Diagnosis of hepatocellular carcinoma (HCC) by at least 1 criterion listed below:\n\n  * Pathologically (histologically or cytologically) proven diagnosis of HCC (strongly recommended)\n  * Radiographically proven (American Association for the Study of Liver Diseases \\[AASLD\\] criteria) diagnosis of HCC by multiphasic MRI and\u002For CT scan is allowed.\n  * For patients with a prior or concurrent malignancy, pathologic confirmation of hepatocellular cancer is required.\n* HCC macrovascular invasion, defined as enhancing vascular thrombosis demonstrating arterial enhancement and venous or delayed venous washout on multiphasic MRI and\u002For CT is required.\n* Presence of extrahepatic metastatic disease on CT chest and CT or MRI pelvis, or PET\u002FCT chest\u002Fabdomen\u002Fpelvis is permitted.\n* 5 or fewer discrete intrahepatic parenchymal foci of HCC.\n* Total maximal sum of hepatocellular carcinoma tumors, as a single conglomerate, multiple lesions, or infiltrative HCC \\\u003C 20 cm in total summed diameter.\n* No direct primary tumor extension into the stomach, duodenum, small bowel, or large bowel.\n* No known fibrolamellar HCC, sarcomatoid HCC, or biphenotypic HCC.\n* Child-Pugh class A or B7 liver function.\n* Age ≥ 18.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n* Not pregnant and not nursing\n\n  * Negative urine or serum pregnancy test (in persons of childbearing potential) within 30 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.\n* Absolute neutrophil count (ANC) ≥ 1,500 cells\u002Fmm\\^3.\n* Platelets ≥ 60,000 cells\u002Fmm\\^3.\n* Hemoglobin ≥ 8g\u002Fdl (Note: The use of transfusion or other intervention to achieve hemoglobin \\[Hgb\\] ≥ 8g\u002Fdl is acceptable).\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 6 x institutional upper limit of normal (ULN).\n* Total bilirubin \\\u003C 4 x institutional ULN.\n* Creatinine clearance (CrCL) ≥ 30 mL\u002Fmin\u002F1.73 m\\^2 by the Cockcroft-Gault formula.\n* For treatment of HCC:\n\n  * Prior surgical resection, transarterial chemoembolization (TACE), and ablation are permitted.\n  * No prior systemic therapy or transarterial radioembolization (TARE) for HCC.\n  * No history of liver transplantation.\n* For prior treatment for any malignancy:\n\n  * Prior systemic therapy for a different cancer is allowable, except for prior immunotherapy.\n  * No prior radiotherapy to the region of the study cancer that would result in significant overlap of radiation therapy fields that would lead to excessive cumulative toxicity at the discretion of the investigator.\n* No medical contraindication to the standard of care immunotherapy.\n* For patients to be treated with atezolizumab\u002Fbevacizumab:\n\n  * No history of a gastrointestinal (GI) bleed or other clinically significant bleeding event within 6 months prior to study registration.\n* Systemic immunostimulatory agents (including, but not limited to, interferons and interleukin-2 \\[IL-2\\]) are prohibited within 4 weeks or five drug elimination half-lives (whichever is longer) prior to registration and during the study period.\n* No history of allergic reaction to the systemic therapy agent(s), compounds of similar chemical or biologic composition to the systemic therapy agent(s) (or any of its excipients).\n* PRIOR TO STEP 2 RANDOMIZATION:\n* Obtain confirmation of payment coverage (insurance or other) for both possible treatment arms.",{"count":52,"type":20},226,[54],"PHASE3","This phase III trial compares the effect of immunotherapy (IO) with stereotactic body radiation therapy (SBRT) to IO alone in treating patients with liver cancer (hepatocellular cancer) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). The usual approach is treatment with IO-based drug combinations, such as atezolizumab and bevacizumab, durvalumab and tremelimumab, or ipilimumab and nivolumab. IO with monoclonal antibodies, such as durvalumab, tremelimumab, atezolizumab, nivolumab and ipilimumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving IO with SBRT may be more effective than IO alone in helping patients with advanced hepatocellular cancer live longer.",[27,29,30],"2026-06-22",{"date":34,"type":35},{"date":60,"type":35},"2026-02-26",{"date":62,"type":20},"2029-03-10",{"name":64,"class":42},"NRG Oncology",139,{"id":67,"slug":68,"hasResults":11,"nctId":69,"briefTitle":70,"officialTitle":71,"acronym":72,"eligibilityCriteria":73,"healthyVolunteers":11,"sex":16,"minAge":74,"maxAge":4,"enrollmentInfo":75,"targetDuration":4,"studyType":21,"phases":77,"briefSummary":78,"conditions":79,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":178,"lastUpdatePostDateStruct":179,"startDateStruct":180,"completionDateStruct":182,"leadSponsor":184,"locationsCount":43},"100459958","phase-1-personalized-neoantigen-peptide-based-vaccine-in-combination-with-pembrolizumab-for-treatment-of-advanced-solid-tumors-100459958","NCT05269381","Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors","A Phase I\u002FII Study of Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab in Advanced Solid Tumors (PNeoVCA)","PNeoVCA","Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.\n\nPHASE I PRE-REGISTRATION, ALL:\n\n* Willing to provide tissue specimens per protocol\n\n  * NOTE: includes fresh tissue specimen at pre-registration for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo Institutional Review Board (IRB) protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration.\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide blood specimens for research\n* Negative pregnancy test =\\\u003C 7 days prior to pre-registration for persons of childbearing potential. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1\n* Anticipated life expectancy \\> 6 months\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).\n* The following lab values obtained =\\\u003C 28 days prior to pre-registration:\n\n  * Hemoglobin \\>= 9.0 g\u002FdL (Must be \\>= 7 days after most recent transfusion)\n  * Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 or \\>= 1.5 X 10\\^9\u002FL\n  * Platelet count \\>= 100,000\u002Fmm\\^3 or \\>= 100 X 10\\^9\u002FL (Must be \\>=7 days after most recent transfusion)\n  * Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN)\n  * Aspartate transaminase (AST) and alanine transaminase (ALT) =\\\u003C 3 x ULN or =\\\u003C 5 x ULN with liver metastases\n  * Creatinine =\\\u003C 1.5 x ULN OR calculated creatinine clearance must be \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n  * International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy\n\nPHASE I REGISTRATION, ALL:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Measurable disease as defined by RECIST (version 1.1) criteria or non-measurable disease\n\n  * NOTE: Tumor lesions in previously irradiated area are not considered measurable disease\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood and tissue specimens for research\n* Willing to return to enrolling institution for follow-up\n* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have also received and progressed on at least one line of prior FDA-approved targeted therapy\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only\n\n  * NOTE: If urine test cannot be confirmed negative, serum pregnancy test will be required\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior to pre-registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status (for laboratory toxicity see specified limits for inclusion) or NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nPHASE II PRE-SCREENING COHORT 3 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of adenocarcinoma of the breast with estrogen receptor (ER) \\\u003C 10%, progesterone receptor (PR) \\\u003C 10%, and HER2 negative based on current American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guideline\n* Stage I-III based on 7th edition of TNM staging system from American Joint Committee on Cancer (AJCC)\n* Evidence of residual disease \\>= 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging for patients who have not had surgery\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Provide written informed consent\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-SCREENING COHORT 4 ONLY:\n\n* ECOG PS 0 or 1\n* Histological confirmation of lung NSCLC\n* No actionable EGFR mutations and ALK fusions\n* Stage II or stage III based on AJCC 8th\n* Tumor \\>= 2 cm on pre-surgery evaluation imaging (residual disease \\>= 2 cm after neoadjuvant therapy on pre-surgery evaluation imaging in patient who receives neoadjuvant therapy) for patients who have not had surgery. Patients with or without neoadjuvant chemotherapy or immunotherapy are allowed\n* Provide written informed consent\n* Willing to proceed with surgery and provide tissue and blood specimens for patients who have not had surgery\n* Willing to return to enrolling institution for follow-up\n\nPHASE II PRE-REGISTRATION COHORT 3 (TNBC) ONLY:\n\n* Histologically confirmed residual cancer burden 2 and 3 in surgical specimens\n\nPHASE II PRE-REGISTRATION COHORT 4 (NSCLC) ONLY:\n\n* Tumor without complete pathologic response is confirmed in pathology\n* Willing to proceed with surgery and provide tissue specimens for complete exome and transcriptome sequencing\n\n  * NOTE: Patients who had sequencing under certain Mayo IRB protocols and neoantigens identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and\u002For registration\n* Negative pregnancy test ≤7 days prior to pre-registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* ECOG PS of 0 or 1\n* Anticipated life expectancy \\> 6 months\n\nPHASE II REGISTRATION:\n\n* Successful sequencing and production of REAL-Neo vaccine\n* Patients will receive \\>= 2 additional cycles of maintenance pembrolizumab\n* ECOG PS 0 or 1\n* Anticipated life expectancy \\> 6 months\n* The following lab values obtained =\\\u003C 14 days prior to registration:\n\n  * Hemoglobin \\>= 9.0 g\u002Fdl\n  * ANC \\>= 1500\u002Fmm\\^3\n  * Platelet count \\>= 100,000\u002Fmm\\^3\n  * Total bilirubin =\\\u003C 1.5 x ULN\n  * ALT and AST =\\\u003C 3 x ULN (=\\\u003C 5 x ULN with liver involvement)\n  * PT\u002FINR and aPTT =\\\u003C 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy\n  * Calculated creatinine clearance \\>= 50 ml\u002Fmin using Cockcroft-Gault formula\n* Provide written informed consent\n* Willing to provide blood specimens for research\n* Willing to return to enrolling institution for follow-up\n* Negative pregnancy test =\\\u003C 14 days prior to registration for persons of childbearing potential only. If urine test cannot be confirmed negative, serum pregnancy test will be required.\n* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle\n* Willing to receive tetanus vaccination if subject has not had one =\\\u003C 1 year prior registration\n* Recovered from all toxicities associated with prior treatment to acceptable baseline status NCI CTCAE version 5.0 Grade of 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo)\n\nExclusion Criteria\n\nALL PHASES:\n\n* Any of the following because study involves investigational agent whose genotoxic, mutagenic and teratogenic effects on developing fetus and newborn are unknown:\n\n  * Pregnant person\n  * Nursing person unwilling to stop breast feeding\n  * Person of childbearing potential unwilling to employ adequate contraception from registration through 6 months after final vaccine cycle\n* Co-morbid systemic illnesses or other severe concurrent disease which, in judgment of investigator, would make patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and toxicity of prescribed regimens\n* History of myocardial infarction =\\\u003C 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.\n* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy\n\nPHASE I PRE-REGISTRATION:\n\n* Acute, reversible effect(s) of prior therapy not recovered to baseline regardless of interval since last treatment\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Congestive heart failure with New York Heart Association (NYHA) class III or IV moderate to severe objective evidence of cardiovascular disease\n  * Stroke =\\\u003C 3 months prior to pre-registration\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered treatment for primary neoplasm, except pembrolizumab\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* History of active autoimmune disease (AD) that required systemic treatment in =\\\u003C 30 days (i.e., use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with celiac disease controlled with diet modification are not excluded PHASE I REGISTRATION\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major Surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n  * Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= Grade 3 treatment-emergent adverse event (TEAE) to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent permitted in absence of active AD\n* Evidence of leptomeningeal disease or central nervous system metastases that are untreated, symptomatic, or require steroids \\>10 mg daily prednisone equivalent\n\n  * NOTE: Patients with history of stable treated brain metastases are eligible. Stable treated metastases defined as no evidence of progression for ≥4 weeks on brain imaging (MRI or CT scan)\n\nPHASE II PRE-SCREENING:\n\n* Uncontrolled illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-screening\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If there is history of prior malignancy, they must not be receiving other specific treatment for their cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-screening\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n\nPHASE II PRE-REGISTRATION\n\n* Uncontrolled illness including, but not limited to:\n\n  * Congestive heart failure with NYHA class III or IV; moderate to severe objective evidence of cardiovascular disease\n  * Significant cardiac arrhythmia or unstable angina\n  * Any other conditions that would limit compliance with study requirements\n* Any prior hypersensitivity or adverse reaction to GM-CSF\n* Other active malignancy =\\\u003C 3 years prior to pre-registration\n\n  * EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix\n  * NOTE: If history of prior malignancy, must not be receiving other specific treatment for cancer\n* Known history of active AD that has required systemic treatment in the =\\\u003C 30 days (i.e., with use of disease modifying agents, corticosteroids \\> 10 mg daily prednisone equivalent, or other immunosuppressive drugs) prior to pre-registration\n\n  * NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded.\n* Patients will also be excluded based on tissue\u002Fribonucleic acid (RNA)\u002Fdeoxyribonucleic acid (DNA) quality and quantity. If any of the following quality and quantity thresholds are not met, patient will be excluded: (1) tumor tissue cellularity equal to or greater than 30%; (2) there are \\>= 2 cores with passing cellularity; (3) \\>= 30% of tumor RNA with fragment sizes are \\>= 200 base pairs (DV200 \\>= 30); (4) \\\u003C 10% of DNA fragments are smaller than 1 kb; and (5) sufficient amount of both DNA (blood and tumor) and RNA (tumor) for exome sequencing and whole transcriptome sequencing (RNAseq) according to Mayo sequencing core. (Kits and technologies change overtime, so these are not fixed numbers.)\n\nPHASE II REGISTRATION\n\n* Evidence of metastatic disease or recurrence\n* Any of the following prior therapies:\n\n  * Chemotherapy, experimental drugs (except pembrolizumab), or small molecules inhibitors (except for endocrine therapies) =\\\u003C 3 weeks prior to registration\n  * Radiation =\\\u003C 2 weeks prior to registration\n  * Major surgery =\\\u003C 4 weeks prior to registration\n  * Received live vaccine =\\\u003C 30 days prior to registration\n\n    * NOTE: Continuation of pembrolizumab per standard of care is allowed\n    * NOTE: Palliative radiation therapy for symptoms control including, but not limited to, bone metastatic lesion radiation therapy is allowed, but last dose of radiation therapy should be \\> 14 days from first dose of vaccination on study\n* CTCAE \\>= grade 3 TEAE to prior checkpoint inhibitor, TEAE requiring systemic corticosteroids (\\> 10 mg daily prednisone equivalent), or permanent treatment discontinuation due to toxicity\n* Neuromuscular disorders (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy), or history of rhabdomyolysis\n* Active ADs that require chronic systemic steroids (\\> 10 mg daily prednisone equivalent) or immunosuppressive agents\n* Requirement for systemic corticosteroids (\\> 10 mg daily prednisone equivalent) or other immunosuppressive medications =\\\u003C 14 days prior to registration\n\n  * NOTE: Inhaled or topical steroids and adrenal replacement steroid doses \\> 10 mg daily prednisone equivalent are permitted in","16 Years",{"count":76,"type":20},132,[23,24],"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.",[80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,29,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,30,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177],"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 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 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","2026-06-18",{"date":32,"type":35},{"date":181,"type":35},"2022-03-31",{"date":183,"type":20},"2028-03-31",{"name":185,"class":42},"Mayo Clinic",{"id":187,"slug":188,"hasResults":11,"nctId":189,"briefTitle":190,"officialTitle":191,"acronym":4,"eligibilityCriteria":192,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":193,"targetDuration":4,"studyType":21,"phases":195,"briefSummary":197,"conditions":198,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":207,"lastUpdatePostDateStruct":208,"startDateStruct":210,"completionDateStruct":212,"leadSponsor":214,"locationsCount":43},"100624088","phase-4-morning-versus-afternoon-administration-of-immunotherapy-for-the-treatment-of-advanced-or-metastatic-solid-tumors-the-knight-shift-study-100624088","NCT07405086","Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study","Knight Cancer Institute Study of Histology-Agnostic Immunotherapy With Focus on Timing: - Knight SHIFT - A Prospective, Multi-Histology Pragmatic Study","Inclusion Criteria:\n\n* Must provide written informed consent before any study-specific procedures or interventions are performed\n* Aged ≥ 18 years\n* Histologically confirmed advanced\u002Fmetastatic solid tumor as follows:\n\n  * Non small cell lung cancer (NSCLC) (driver-negative, immune checkpoint inhibitor \\[ICI\\]-eligible)\n  * Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) (platinum-eligible),\n  * Renal cell carcinoma (RCC)\n  * Biliary-tract cancer (BTC)\n  * Hepatocellular carcinoma (HCC)\n  * Melanoma\n* Planned to receive a Food and Drug Administration (FDA)-approved immune check point inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-CTLA4) regimen for the treatment of their malignancy\n* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1\n\nExclusion Criteria:\n\n* Prior ICI-based regimen for treatment of cancer\n* Current or prior use of immunosuppressive medication within 28 days before planned standard-of-care immunotherapy infusion, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses not exceeding 10 mg\u002Fday of prednisone (or equivalent corticosteroid)\n* Uncontrolled autoimmune disease requiring immunosuppression\n* Active, uncontrolled central nervous system (CNS) metastases",{"count":194,"type":20},160,[196],"PHASE4","This phase IV trial is evaluating whether morning versus afternoon administration of standard of care immunotherapy impacts its effectiveness in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Circadian rhythm refers to the internal biological clock in which various processes in the body, including immune cell activity, are controlled by the time of day. Exactly how this works is not fully understood, and the researchers want to see if circadian rhythm control of the immune system can influence response to immunotherapy based on whether it is given in the morning (before 11:00 am) or afternoon (12:00pm). The time of day that immunotherapy is given (morning versus afternoon) may impact the effectiveness in treating patients with advanced or metastatic solid tumors.",[199,200,27,201,202,203,204,205,120,121,122,123,124,126,206,29,132,133,30,148,149],"Advanced Biliary Tract Carcinoma","Advanced Head and Neck Squamous Cell Carcinoma","Advanced Lung Non-Small Cell Carcinoma","Advanced Malignant Solid Neoplasm","Advanced Melanoma","Advanced Renal Cell Carcinoma","Metastatic Biliary Tract Carcinoma","Recurrent Head and Neck Squamous Cell Carcinoma","2026-06-10",{"date":209,"type":35},"2026-06-12",{"date":211,"type":35},"2026-06-08",{"date":213,"type":20},"2028-12-31",{"name":215,"class":42},"OHSU Knight Cancer Institute",{"id":217,"slug":218,"hasResults":11,"nctId":219,"briefTitle":220,"officialTitle":221,"acronym":4,"eligibilityCriteria":222,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":223,"targetDuration":4,"studyType":21,"phases":225,"briefSummary":226,"conditions":227,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":231,"lastUpdatePostDateStruct":232,"startDateStruct":234,"completionDateStruct":236,"leadSponsor":238,"locationsCount":240},"100500068","phase-1-au409-for-the-treatment-of-advanced-primary-liver-cancers-or-solid-tumor-with-liver-metastatic-disease-100500068","NCT05791448","AU409 for the Treatment of Advanced Primary Liver Cancers or Solid Tumor With Liver Metastatic Disease","First in Human Dose Escalation Study of AU409 in Patients With Advanced Primary Liver Cancers or Advanced Solid Tumor With Liver Predominant Metastatic Disease","Inclusion Criteria:\n\n* Age \\>= 18 years old\n* Patients must have histopathologically \u002Fcytologically confirmed advanced solid tumor, which is refractory to standard therapeutic options, or for which there are no standard therapeutic options. Failure of all approved therapies that have a marginal impact on survival is not required as long as the treating physician considers that treatment on study is appropriate for the subject and documents that the subject elects to defer the approved therapies\n* During the dose-escalation portion, patients must have primary liver malignancy (including hepatocellular carcinoma or cholangiocarcinoma) OR a solid tumor with liver dominant disease; liver dominant disease is defined as the majority of the tumor burden being in the liver per investigator assessment AND no more than two extrahepatic sites of disease (site of disease refers to organ or system). During the dose expansion portion of the study, eligibility may be limited to one or more tumor types depending on findings from the dose-escalation phase; this will be clarified in an amendment\n* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Patient must have recovered from any toxic effects of previous chemotherapy, targeted therapy or radiotherapy as judged by the Investigator to =\\\u003C grade 1 (except for alopecia). Residual sensory neuropathy =\\\u003C grade 2 is allowed. Residual endocrine adverse events (such as hypothyroidism or hypoadrenalism) that are manageable with replacement therapy are allowed\n* Previous chemotherapy\u002Fradiotherapy\u002Ftargeted\u002Fimmunotherapy therapy should have been completed at least 4 weeks prior to start of AU409 administration, or five half-lives, whichever is shorter (except for palliative radiation therapy that should be completed \\>= 14 days prior to study entry)\n* Patients must have an estimated life expectancy of at least 3 months\n* Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. A male participant must agree to use highly effective contraception during the intervention period and for 60 days after the last dose of AU409 and refrain from donating sperm during this period. WOCBP are eligible to participate if they are not pregnant, not breastfeeding, and agree to follow the contraceptive guidance during the study intervention period and for at least 90 days after the last dose of AU409\n\n  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately\n* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)\n* Patients must agree, as part of the informed consent, to undergo liver biopsy (for a subset of patients enrolled at and above dose level 4) and to provide blood for pharmacokinetics analysis\n* Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3\n* Platelet count \\>= 100,000\u002Fmm\\^3\n* Hemoglobin \\>= 8 g\u002FdL (prior transfusion is allowed if completed 2 weeks prior to screening and hemoglobin remains \\>= 8 g\u002FdL)\n* For patients with HCC with splenic sequestration: ANC \\>= 1000\u002Fmm\\^3\n* For patients with HCC with splenic sequestration: Platelets \\>= 70,000\n* Calculated clearance \\>= 60 mL\u002Fmin\u002F1.73 m\\^2. Actual body weight should be used for calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For subjects with a Body Mass Index (BMI) \\> 30 kg\u002Fm\\^2, lean body weight should be used instead\n* Total bilirubin =\\\u003C 1.5 X upper limit of normal (ULN) (subjects with known Gilbert's hepatic function disease can have bilirubin of up to 2 X ULN)\n* Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) =\\\u003C 3 X ULN; or AST\u002FALT =\\\u003C 5 X ULN if patient has liver tumors\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) =\\\u003C 1.8 times upper limit of normal (unless patient is on anticoagulation)\n\nExclusion Criteria:\n\n* Patients who have had hypersensitivity to pentamidine or any excipients of AU409\n* Treatment with other anticancer therapies (including surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation therapy, etc.) or investigational therapy within 28 days prior to study entry (except for palliative radiation therapy that should be completed \\>= 14 days prior to study entry)\n* Hepatocellular carcinoma patients with a Child Pugh score \\>= B7\n* Patients with known central nervous system metastases which are untreated or symptomatic; patients with treated brain metastases (completed \\>= 30 days prior to screening) are allowed provided they are asymptomatic and are off steroids\n* Patient with a history of the following within 6 months prior to cycle 1 day 1: a myocardial infarction, severe\u002Funstable angina pectoris, coronary\u002Fperipheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia, cerebrovascular accident, transient ischemic attack, or seizure disorder. Atrial fibrillation is allowed if rate is controlled\n* Patients who have corrected QT (QTc) interval to \\> 470 msec (Fredericia's equation) on 2 out of 3 electrocardiogram (ECG)'s (if first ECG has QTc \\\u003C 470, no need to repeat, if first ECG has QTc \\> 470 repeat twice for a total of 3 ECG's)\n* Patients who are on therapeutic anticoagulation with warfarin; however, patients on therapeutic doses of with low molecular weight heparins or Factor Xa inhibitors are eligible\n* Patient with history of gastrointestinal surgery or malabsorptive conditions that may change the absorption of drugs and\u002For cause rapid transit (such as total gastrectomy, small bowel resection, etc.)\n* Patients who have known active hepatitis B. Patients with chronic hepatitis B who are on anti-viral therapy and have a hepatitis B viral load of =\\\u003C 500 IU\u002FmL are allowed on the study. Patients with chronic Hepatitis C are allowed\n* Patients who have active infection requiring treatment (except hepatitis B and C as noted above) including known human immunodeficiency virus (HIV) infection\n* Patients who have concurrent conditions resulting in immune compromise, including chronic treatment with corticosteroids or other immunosuppressive agents\n* Patients who have any other condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results\n* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants\n* Patients who are on medications that are considered to be strong inducers or inhibitors of the cytochrome P450 isoenzymes should have such medications discontinued or replaced. Such medications should be avoided for one week prior to first dose of treatment and during the trial participation. If these medications are absolutely necessary for the patient and cannot be replaced, enrollment may still be considered on a case by case basis if it is in the patient's best interest and after discussion with the principal investigator (PI)",{"count":224,"type":20},36,[23],"This phase I trial tests the safety, side effects, and best dose of a new intervention, AU409, in treating patients with primary liver cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or advanced solid tumors that have spread to the liver (liver metastatic disease). AU409 may stop cancer from growing and spreading. This trial may help researchers determine if AU409 is safe and effective in treating patients with liver cancers and solid tumors with liver metastatic disease.",[228,27,202,229,230,29,30],"Advanced Cholangiocarcinoma","Metastatic Malignant Neoplasm in the Liver","Refractory Malignant Solid Neoplasm","2026-05-29",{"date":233,"type":35},"2026-06-01",{"date":235,"type":35},"2023-03-29",{"date":237,"type":20},"2028-03-29",{"name":239,"class":42},"University of Southern California",2,{"id":242,"slug":243,"hasResults":11,"nctId":244,"briefTitle":245,"officialTitle":246,"acronym":4,"eligibilityCriteria":247,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":248,"targetDuration":4,"studyType":21,"phases":250,"briefSummary":251,"conditions":252,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":253,"lastUpdatePostDateStruct":254,"startDateStruct":256,"completionDateStruct":258,"leadSponsor":260,"locationsCount":263},"100578424","phase-1-testing-the-addition-of-an-anti-cancer-drug-sapanisertib-to-the-usual-chemotherapy-treatment-cabozantinib-in-metastatic-liver-cell-cancer-with-a-change-in-genes-for-the-protein--catenin-the-saphire-trial-100578424","NCT06811116","Testing the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial","A Phase I\u002FII Trial of Sapanisertib in Combination With Cabozantinib in β-catenin-mutated Hepatocellular Carcinoma (SAPHIRE)","Inclusion Criteria:\n\n* Patients must have histologically or cytologically confirmed HCC, not amenable to curative treatment approach\n* For Phase 2, patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam\n* For phase 2, patients must have a β-catenin mutation, based on next generation eequencing (NGS) testing through Clinical Laboratory Improvement Amendments (CLIA)-certified commercially available standard of care assay\n* Patients must have received at least one prior line of systemic therapy in the metastatic setting, including a prior immune checkpoint inhibitor therapy unless not eligible. For the phase 2 portion, patients must have received at least one and no more than two prior lines of systemic therapy in the metastatic setting, including a prior immune checkpoint inhibitor therapy unless not eligible\n* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of sapanisertib in combination with cabozantinib in patients \\\u003C18 years of age, children are excluded from this study\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)\n* Child Pugh score of A\n* Absolute neutrophil count ≥ 1,000\u002FmcL\n* Platelets ≥ 30,000\u002FmcL\n* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 5 × institutional ULN\n* Glomerular filtration rate (eGFR) ≥ 40 mL\u002Fmin\u002F1.73 m\\^2\n* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated\n* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression\n* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy\n* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better\n* For the phase 2 portion, availability of archival tumor tissue at the time of patient enrollment for banking for molecular profiling studies\n* The effects of sapanisertib and cabozantinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and after completion of drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Both men and women treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and for the following duration after completion of sapanisertib and cabozantinib administration:\n\n  * 90 days and 120 days after last dose of sapanisertib for women of childbearing potential and men respectively,\n  * 5 months and 7 months after last dose of cabozantinib for women of childbearing potential and men respectively\n* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants\n\nExclusion Criteria:\n\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> grade 1) with the exception of alopecia\n* Patients who are receiving any other investigational agents\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to sapanisertib and cabozantinib\n* Use of strong CYP3A4-inhibiting agents due to drug-drug interaction with cabozantinib\n* Prior exposure to cabozantinib\n* Patients who are unable to swallow oral medications such as capsules and tablets and patients with gastrointestinal conditions that may affect the absorption of oral medications\n* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous\n* Pregnant women are excluded from this study because sapanisertib and cabozantinib have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sapanisertib and cabozantinib, breastfeeding should be discontinued if the mother is treated with sapanisertib and cabozantinib",{"count":249,"type":20},92,[23,24],"This phase I\u002FII trial studies the side effects and best dose of sapanisertib when given together with cabozantinib, and to see how well they work in treating patients with liver cancer that has spread from where it first started to other places in the body (metastatic) and contains a mutation (change) in the β-catenin gene. Sapanisertib and cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving sapanisertib and cabozantinib together may work better than giving cabozantinib alone in treating β-catenin-mutated metastatic hepatocellular carcinoma.",[27,121,29,30],"2026-05-12",{"date":255,"type":35},"2026-05-13",{"date":257,"type":35},"2025-11-17",{"date":259,"type":20},"2027-08-31",{"name":261,"class":262},"National Cancer Institute (NCI)","NIH",4,{"id":265,"slug":266,"hasResults":11,"nctId":267,"briefTitle":268,"officialTitle":269,"acronym":4,"eligibilityCriteria":270,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":271,"targetDuration":4,"studyType":21,"phases":273,"briefSummary":274,"conditions":275,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":279,"lastUpdatePostDateStruct":280,"startDateStruct":282,"completionDateStruct":284,"leadSponsor":286,"locationsCount":43},"100358074","phase-1-modified-immune-cells-autologous-dendritic-cells-and-a-vaccine-prevnar-combined-with-immune-checkpoint-inhibition-after-high-dose-external-beam-radiation-therapy-in-treating-patients-with-unresectable-liver-cancer-100358074","NCT03942328","Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) Combined With Immune Checkpoint Inhibition After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer","MC1641 Phase II Study Of Intratumoral Injection Of Autologous Dendritic Cells Combined With Immune Checkpoint Inhibition After High-Dose Conformal External Beam Radiotherapy In Patients With Unresectable Primary Liver Cancer","Inclusion Criteria:\n\n* Age \\>= 18 years\n* Pilot study (group 1): Histologic confirmation of intrahepatic CCA (Closed as of amendment 3)\n* Phase II study (group 2): Histologic and\u002For radiologic confirmation of hepatocellular carcinoma (HCC)\n* Phase II study (group 3): Histologic confirmation of intrahepatic cholangiocarcinoma (iCCA)\n* The following tumor characteristics must be met\n\n  * Unresectable disease: HCC (group 2) or intrahepatic CCA (group 3)\n  * Measurable or evaluable disease\n  * All lesions should be treatable by EBRT while meeting normal tissue constraints\n  * Tumor lesions should be accessible using an ultrasound (US)-guided approach for intratumoral DC injection\n  * No evidence of extrahepatic tumor (excluding tumor thrombus) by computed tomography (CT) or magnetic resonance imaging (MRI) scan\n\n    * NOTE: Patients who are not candidates for surgical treatment or for ablation with curative intent are allowed\n* Good candidate for standard of care high-dose conformal EBRT in the view of the investigator\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1\n* GROUP 2 HCC ONLY: Absolute neutrophil count (ANC) \\>= 1000\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Absolute lymphocyte count (ALC) \\>= 500\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Absolute monocyte count (AMC) \\>= 300\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Platelet count \\>= 50,000\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Hemoglobin \\>= 9.0 g\u002FdL (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Total bilirubin \\\u003C 1.5 mg\u002FdL (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\\\u003C 5 x upper limit of normal (ULN) (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Creatinine =\\\u003C 2 mg\u002FdL (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Prothrombin time (PT)\u002Finternational normalized ratio (INR)\u002Factivated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN (obtained =\\\u003C 15 days prior to registration)\n* GROUP 2 HCC ONLY: Absence of proteinuria at screening as demonstrated by one of the following:\n\n  * Urine protein\u002Fcreatinine (UPC) ratio \\\u003C 1.0 at screening OR\n  * Urine dipstick for proteinuria \\\u003C 2+ (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 to be eligible)\n* GROUP 3 iCCA ONLY: Absolute neutrophil count (ANC) ≥ 1000\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: Absolute lymphocyte count ≥ 500\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: Absolute monocyte count ≥ 300\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: Platelet count ≥ 50,000\u002Fmm\\^3 (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: Hemoglobin ≥ 9.0 g\u002FdL (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: Total bilirubin \\\u003C 1.5 x ULN (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤ 2.5 x ULN (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: Creatinine ≤ 2 mg\u002FdL (obtained =\\\u003C 15 days prior to registration)\n* GROUP 3 iCCA ONLY: PT\u002FINR\u002FaPTT ≤ 1.5 x ULN (obtained =\\\u003C 15 days prior to registration)\n\n  * NOTE: If patient is receiving therapeutic anticoagulation, patient must be on a stable anticoagulant regimen\n* Ability to provide written consent\n* Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)\n* Willingness to provide blood and tissue samples for correlative research purposes\n\nExclusion Criteria:\n\n* Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown:\n\n  * Pregnant persons\n  * Nursing persons\n  * Persons of childbearing potential who are unwilling to employ highly effective contraception during heterosexual intercourse while on this study and for 5 months after the last dose of study medication\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Immunocompromised patients and patients known to be HIV positive.\n\n  * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial if they are stable on anti-retroviral therapy, have a CD4+ T cell count ≥ 200\u002FuL, and have an undetectable viral load\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection requiring systemic treatment or that could impact patient safety\n  * Severe infection ≤ 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia\n  * Significant cardiovascular disease (New York Heart Association \\[NYHA\\] class II), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia\n  * Or, psychiatric illness\u002Fsocial situations (e.g., substance abuse) that would limit compliance with study requirements\n* Receiving any other investigational agent that would be considered a treatment for the primary neoplasm\n* Other active malignancy =\\\u003C 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes\n* Major surgery =\\\u003C 4 weeks prior to enrollment (other than diagnostic surgery or surgical spacer placement in preparation for radiation treatment), or anticipation of need for a major surgical procedure during the study\n* History of hypersensitivity or anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid\n* Active or history of autoimmune disease or immune deficiency, including but not limited to,myasthenia gravis, myositis, autoimmune hepatitis, Crohn's disease, inflammatory bowel disease, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjogren syndrome, systemic lupus erythematosus, Guillain-Barre syndrome, multiple sclerosis, Wegener granulomatosis, or similar conditions\n\n  * NOTE: Exceptions are allowed for:\n\n    * Patients with hypothyroidism on thyroid replacement therapy\n    * Patients with type 1 diabetes mellitus on insulin regimen\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 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      * There has been 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 ≤ 12 months prior to registration\n* Requires anticoagulant treatment (INR \\> 1.5 x ULN) or use of anti-platelet agents that cannot be discontinued for the intratumoral injection procedure\n\n  * NOTE: Heparin for line patency without detectable lab abnormalities in coagulation will be allowed\n* Corticosteroids =\\\u003C 2 weeks prior to registration, including oral, intravenous (IV), subcutaneous, or inhaled routes of administration\n\n  * NOTE: Patients on chronic corticosteroids for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg\u002Fday of prednisone (or equivalent)\n  * NOTE: Exception allowed for patients who need prophylactic steroids prior to imaging for contrast allergies\n\n    * Exception: Patients 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    * Exception: Patients 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 for the study\n* History of myocardial infarction =\\\u003C 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias\n* Child Pugh class B or C cirrhosis of the liver\n* Previously received immune modulating therapies including but not limited to immune checkpoint inhibitors targeting PD-1 PDL-1 CTLA4, etc.; or prior dendritic cell therapy\n* Prior liver radiation, including radioembolization\n* GROUP 2 ONLY: Barcelona Clinic Liver Cancer (BCLC) stage D disease\n* GROUP 2 ONLY: History of untreated high-risk gastroesophageal varices\n* Active tuberculosis\n* Treatment with therapeutic oral or IV antibiotics ≤ 2 weeks prior to registration\n\n  * NOTE: Exception for patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study\n* Prior allogeneic stem cell or solid organ transplantation\n* Treatment with a live, attenuated vaccine ≤ 4 weeks prior to registration",{"count":272,"type":20},85,[23,24],"This early phase I trial studies the side effects of autologous dendritic cells and a vaccine called Prevnar in combination with immune checkpoint inhibition (with bevacizumab and atezolizumab or druvalumab) in treating patients liver cancer that cannot be removed by surgery (unresectable) after undergoing standard high-dose external beam radiotherapy. Autologous dendritic cells are immune cells generated from patients' own white blood cells that are grown in a special lab and trained to stimulate the immune system to destroy tumor cells. A pneumonia vaccine called Prevnar may also help stimulate the immune system. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab and durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving autologous dendritic cells and Prevnar in combination with immune checkpoint inhibition after radiotherapy may be safe, and tolerable and may stimulate the body's own immune system to fight against the tumor in patients with unresectable liver cancer.",[29,276,30,277,164,278],"Stage III Intrahepatic Cholangiocarcinoma AJCC v8","Stage IV Intrahepatic Cholangiocarcinoma AJCC v8","Unresectable Intrahepatic Cholangiocarcinoma","2026-04-16",{"date":281,"type":35},"2026-04-20",{"date":283,"type":35},"2019-09-19",{"date":285,"type":20},"2029-08-31",{"name":185,"class":42},{"id":288,"slug":289,"hasResults":11,"nctId":290,"briefTitle":291,"officialTitle":292,"acronym":4,"eligibilityCriteria":293,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":294,"targetDuration":4,"studyType":21,"phases":296,"briefSummary":297,"conditions":298,"keywords":4,"overallStatus":299,"whyStopped":4,"lastUpdateSubmitDate":37,"lastUpdatePostDateStruct":300,"startDateStruct":302,"completionDateStruct":304,"leadSponsor":306,"locationsCount":43},"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":295,"type":20},40,[24],"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.",[102,29,30,164],"NOT_YET_RECRUITING",{"date":301,"type":35},"2026-04-06",{"date":303,"type":20},"2026-04-02",{"date":305,"type":20},"2027-08-01",{"name":215,"class":42},{"id":308,"slug":309,"hasResults":11,"nctId":310,"briefTitle":311,"officialTitle":312,"acronym":4,"eligibilityCriteria":313,"healthyVolunteers":11,"sex":16,"minAge":314,"maxAge":4,"enrollmentInfo":315,"targetDuration":4,"studyType":21,"phases":317,"briefSummary":318,"conditions":319,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":321,"lastUpdatePostDateStruct":322,"startDateStruct":324,"completionDateStruct":326,"leadSponsor":328,"locationsCount":43},"100391712","phase-1-nivolumab-fluorouracil-and-interferon-alpha-2b-for-the-treatment-of-unresectable-fibrolamellar-cancer-100391712","NCT04380545","Nivolumab, Fluorouracil, and Interferon Alpha 2B for the Treatment of Unresectable Fibrolamellar Cancer","A Phase I\u002FII Study of Nivolumab Plus 5-Fluorouracil Plus Interferon-α2b for Unresectable Fibrolamellar Hepatocellular Carcinoma","Inclusion Criteria:\n\n* Patients, or their legal guardian, must give written informed consent prior to initiation of therapy, and patients under age 18 must give assent in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy\n* Patients with histologically confirmed FLHCC (or with documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable). The determination of resectability status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient. The definition of resectability is as follows: hepatectomy can achieve a negative margin while preserving more than 30% of the total estimated liver volume, sparing two contiguous hepatic segments, and maintaining vascular inflow, vascular outflow, and biliary drainage. Patients with extrahepatic disease are defined as having unresectable disease\n* Patient must have measurable disease defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures \\>= 15 mm with conventional techniques or \\>= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan\n* Eastern Cooperative Oncology Group performance status (ECOG PS =\\\u003C 1), or for patients under age 18 Karnofsky performance status of \\>= 70\n* No advanced cirrhosis, with Child-Pugh A\n* Absolute neutrophil count (ANC) \\>= 1,000 \u002Fmm\\^3 (within 14 days of the first dose of study drug)\n* Platelets \\>= 100,000 \u002Fmm\\^3 (within 14 days of the first dose of study drug)\n* Hemoglobin \\> 9.0 g\u002FdL (may be transfused or receive epoetin alfa \\[e.g., Epogen\\] to maintain or exceed this level) (within 14 days of the first dose of study drug)\n* Total bilirubin =\\\u003C 1.5 mg\u002FdL (within 14 days of the first dose of study drug)\n* Serum creatinine =\\\u003C 1.5 times the upper limit of normal (ULN) or estimated creatinine clearance (CrCL) \\> 40 mL\u002Fmin (within 14 days of the first dose of study drug)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\]) and\u002For alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 5 times institutional ULN (within 14 days of the first dose of study drug)\n* Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug\n* Women must not be breastfeeding\n* WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 30 days (duration of ovulatory cycle) for a total of 5 months post treatment completion\n* Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion\n* Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as described in these sections. Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception, which have a failure rate of \\\u003C 1% per year when used consistently and correctly. At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below:\n\n  * HIGHLY EFFECTIVE METHODS OF CONTRACEPTION:\n\n    * Male condoms with spermicide\n    * Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices such as Mirena by WOCBP subject or male subject's WOCBP partner\n    * Nonhormonal intrauterine devices, such as ParaGard\n    * Tubal ligation\n    * Vasectomy\n    * Complete Abstinence\n\n      * Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Abstinence is only acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, profession of abstinence for entry into a clinical trial, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence\n  * LESS EFFECTIVE METHODS OF CONTRACEPTION:\n\n    * Diaphragm with spermicide\n    * Cervical cap with spermicide\n    * Vaginal sponge\n    * Male condom without spermicide\n    * Progestin-only pills by WOCBP subject or male subject's WOCBP partner\n    * Female condom\n\n      * A male and female condom must not be used together\n\nExclusion Criteria:\n\n* Any other malignancy from which the patient has been disease-free for less than 2 years, except for non-melanoma skin cancer, or in situ carcinoma of any site\n* Patients who have organ allografts\n* Patients who have had a major surgical procedure, open biopsy, or significant traumatic injury with poorly healed wound within 6 weeks prior to first dose of study drug; or have an anticipated need for major surgical procedure during the course of the study (other than defined by protocol). NOTE: Patients will be allowed to start cycle 1 day 1 therapy after 24 hours from pre-treatment biopsy\n* Autoimmune disease: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \\[scleroderma\\], systemic lupus erythematosus, autoimmune vasculitis \\[e.g., Wegener's granulomatosis\\])\n* Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome\n* Any underlying medical condition, which in the opinion of the investigator will make the administration of study drug hazardous or will obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea\n* Patients who have had a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, gastrointestinal obstruction, or abdominal carcinomatosis which are known risks factors for bowel perforation\n* Patients who have a primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke within the past year\n* History of serious systemic disease, including myocardial infarction or unstable angina within the last 12 months, history of hypertensive crisis or hypertensive encephalopathy, uncontrolled hypertension (blood pressure of \\> 140\u002F90 mmHg) at the time of enrollment, New York Heart Association grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or significant vascular disease or symptomatic peripheral vascular disease\n* Patients who have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications\n* Patients who have received any live or attenuated viral vaccines within a month prior to initiation of study drugs\n* Patients who have active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening\n\n  * Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test and negative HBV deoxyribonucleic acid (DNA) test at screening, are eligible for the study\n* Patients who have active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test at screening\n\n  * The HCV RNA test will be performed only for patients who have a positive HCV antibody test\n* Patients who have clinical history of coagulopathy, bleeding diathesis, or thrombosis within the past year\n* Patients who have a serious, non-healing wound, ulcer, or bone fracture\n* Patients who are pregnant (positive pregnancy test) or lactating\n* Patients with prior orthotropic liver transplantation\n* Patients with cirrhosis and severe synthetic liver dysfunction (Child Pugh B-C)\n* Patients must not have received prior anticancer therapy with anti-PD-1 for FLHCC treatment. Patients receiving any concomitant systemic therapy for FLHCC are excluded\n* Patients must not be scheduled to receive another experimental drug while on this study\n* Patients who require ongoing anticoagulation will be excluded. Only aspirin will be permitted. Pre and post-surgical prophylactic anti-coagulation treatment is permitted\n* Patients must not require total parenteral nutrition\n* Patients who are on high dose steroid (e.g. \\> 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g. infliximab). Corticosteroid use will only be allowed during trial participation for grade 3\u002F4 AEs or hypersensitivity reactions\n* Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study","12 Years",{"count":316,"type":20},15,[23,24],"This phase I\u002FII trial studies the side effects and how well nivolumab, fluorouracil, and interferon alpha 2b work for the treatment of fibrolamellar cancer (liver cell cancer) that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Interferon alpha 2b may help stimulate the immune system to fight cancer. Giving nivolumab, fluorouracil, and interferon alpha 2b may work better in treating unresectable fibrolamellar cancer compared to fluorouracil and interferon alpha 2b alone.",[29,135,139,30,151,155,320],"Unresectable Fibrolamellar Carcinoma","2026-03-04",{"date":323,"type":35},"2026-03-06",{"date":325,"type":35},"2021-01-13",{"date":327,"type":20},"2028-02-28",{"name":329,"class":42},"M.D. Anderson Cancer Center",{"id":331,"slug":332,"hasResults":11,"nctId":333,"briefTitle":334,"officialTitle":335,"acronym":4,"eligibilityCriteria":336,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":337,"targetDuration":4,"studyType":21,"phases":339,"briefSummary":340,"conditions":341,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":342,"lastUpdatePostDateStruct":343,"startDateStruct":345,"completionDateStruct":347,"leadSponsor":349,"locationsCount":263},"100606362","phase-2-celecoxib-durvalumab-and-tremelimumab-for-the-treatment-of-patients-with-advanced-or-metastatic-liver-cancer-100606362","NCT07174570","Celecoxib, Durvalumab and Tremelimumab for the Treatment of Patients With Advanced or Metastatic Liver Cancer","Repurposing Celecoxib to Overcome Resistance to Immunotherapy in Advanced HCC (RECON Study)","Inclusion Criteria:\n\n* Histologically or cytologically confirmed hepatocellular cancer (HCC) planned for treatment at gastrointestinal clinics of Emory University's Winship Cancer Institute or Grady Cancer Center\n* Radiologically measurable disease based on Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1\n* Age ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)\n* Platelet count \\> 100,000 cells\u002F ul (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Hemoglobin (Hb) \\> 9g\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Absolute neutrophil count \\> 1000 cells\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Albumin \\> 3g\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Total bilirubin \\\u003C 3mg\u002Fdl (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Glomerular filtration rate (GFR) \\> 60ml\u002Fmin (based on creatine, and cystatin C estimation where applicable) (within 28 days of cycle 1 day 1, at the discretion of the investigator)\n* Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy\n* FCBP and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n\n  \\* A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n* Completion of all previous cancer directed therapy (including, radiotherapy, liver lesion ablation, bland or chemoembolization and transarterial radioembolization therapy) ≥ 4 weeks before the start of study therapy.\n* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class IIB or better.\n\n  * Patients without existing cardiac disease that could raise the risk of complications who consent for the trial will proceed with trial participation\n  * Patients with existing cardiac disease that could raise the risk of complications will be referred at the discretion of the investigator to a cardio-oncologist or general cardiologist for cardiac optimization prior to starting celecoxib\n* Life expectancy \\> 12 weeks as determined by the investigator\n* Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. This includes willingness to undergo mandatory blood sample draws for evaluation of correlatives\n* Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.\n\nExclusion Criteria:\n\n* Mild to moderate liver dysfunction evidenced by Child Pugh score 7B and above\n* History of arterial or venous thromboembolic events or gastrointestinal bleeding event. Subjects with portal venous thrombosis are permitted in the study if their treating oncologist does not deem it necessary to treat this with heparin products or direct acting anticoagulant (DOAC)\n* Current use of warfarin, heparin products and DOACs\n* Subjects with a history of (non-bleeding) peptic ulcer disease who have been on a proton pump inhibitor for less than 30 days prior to screening visit\n* Patients who have had immune checkpoint inhibitors (ICI) therapy within 6 months prior to entering the study or those who have not recovered from adverse events due to liver directed therapy administered more than 4 weeks earlier (i.e., have residual toxicities \\> grade 2)\n* Patients who are receiving any other investigational agents or an investigational device within 28 days before administration of first dose of study drugs\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study\n* Contraindication to ICI per investigator discretion\n* Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; or uncontrolled grade ≥ 3 hypertension (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥ 160 mmHg) despite antihypertensive therapy\n* Contraindication to non-steroidal anti-inflammatory drugs (NSAIDs): cardiac conditions that significantly raise the risk of cardiopulmonary complications, including unstable angina, uncontrolled heart failure, recent gastrointestinal (GI) bleed. Note that patients who are stable on low dose aspirin (\\\u003C 325mg\u002Fday) only will be allowed on study\n* Current use of other NSAIDs.",{"count":338,"type":20},39,[24],"This phase II trial tests how well the combination of celecoxib with durvalaumab and tremellimumab works in treating patients with hepatocellular cancer (liver cancer) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents and is used to reduces pain. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving celecoxib with durvalaumab and tremellimumab may better treat patients with advanced or metastatic liver cancer.",[27,121,29,30],"2026-01-26",{"date":344,"type":35},"2026-01-28",{"date":346,"type":35},"2026-01-02",{"date":348,"type":20},"2027-11-13",{"name":350,"class":42},"Emory University",{"id":352,"slug":353,"hasResults":11,"nctId":354,"briefTitle":355,"officialTitle":355,"acronym":4,"eligibilityCriteria":356,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":357,"targetDuration":4,"studyType":21,"phases":359,"briefSummary":360,"conditions":361,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":411,"lastUpdatePostDateStruct":412,"startDateStruct":414,"completionDateStruct":416,"leadSponsor":418,"locationsCount":43},"100446356","phase-1-phase-i-study-of-tumor-treating-fields-ttf-in-combination-with-cabozantinib-or-with-pembrolizumab-and-nab-paclitaxel-in-patients-with-advanced-solid-tumors-involving-the-abdomen-or-thorax-100446356","NCT05092373","Phase I Study of Tumor Treating Fields (TTF) in Combination With Cabozantinib or With Pembrolizumab and Nab-Paclitaxel in Patients With Advanced Solid Tumors Involving the Abdomen or Thorax","Inclusion Criteria:\n\n* Participants must have pathologically confirmed advanced\u002Fmetastatic solid cancer (hepatocellular carcinoma, renal cell carcinoma, breast cancer, ovarian\u002Ffallopian, or endometrial\u002Fprimary peritoneal tumors) involving the abdomen or thorax, cannot tolerate standard therapy or have experienced tumor progression on standard therapy.\n* Age: ≥18 years.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.\n* Life expectancy \\>3 months.\n* Normal bone marrow function, defined as absolute neutrophil count ≥1,000\u002FµL; platelets ≥75,000\u002FµL; hemoglobin ≥8 g\u002FdL.\n* Adequate hepatic function as defined by a total bilirubin level ≤1.5 x the upper limit of normal (ULN), unless the patient has known Gilbert's syndrome, and alanine aminotransferase (ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤2.5 x ULN (unless the patient has liver metastases: ALT)\u002F serum glutamic pyruvic transaminase levels (SGPT) ≤5 x ULN).\n* Participants with HCC must have a Child Pugh status A, no clinically significant ascites (requiring pharmacological or interventional treatment), and no history (or increased risk) of esophageal\u002Fgastric bleeding, impaired wound healing, perforation or fistula.\n* Serum creatinine clearance ≥50 mL\u002Fmin by the Cockcroft-Gault formula.\n* Measurable disease by RECIST or evaluable disease.\n* Contraception: Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months and who have not had a tubal ligation, hysterectomy, or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. Male participants must agree to use effective contraception or abstinence while on study.\n* Able to operate the TTF device independently or with the help of a caregiver.\n\nExclusion Criteria:\n\n* Participants must not receive prior anticancer therapy or radiation therapy within 2 weeks and must not undergo major surgery within 4 weeks prior to initiation of treatment on protocol. Participants who are already on cabozantinib and have progressive disease are allowed to transition to treatment with tumor treating fields and cabozantinib. Participants in both cohorts who already started treatments as standard of care (Cohort 1: Cabozantinib and Cohort 2: nab-paclitaxel and Pembrolizumab) are allowed to start on protocol within the first 2-3 weeks of treatment initiation. Palliative radiation therapy is allowed.\n* Participants must have recovered to Grade 0-1 toxicity from prior therapy.\n* Active brain metastasis or leptomeningeal disease. Patients with treated brain metastasis must have stable disease, evidenced by brain imaging for at least 4 weeks and the patient must have been off steroids for at least 2 weeks.\n* The patient has cardiac conditions as follows: uncontrolled: hypertension (blood pressure \\[BP\\] \\> 160\u002F100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association Class II or above), prior or current cardiomyopathy, uncontrolled atrial fibrillation with heart rate \\> 100 beats per minute (bpm), unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment or angina requiring use of nitrates more than once weekly).\n* The patient has concurrent severe and\u002For uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease).\n* Concurrent malignancies are permitted if (A) they were previously treated, and all treatment of that malignancy was completed at least 2 years before enrollment and no evidence of disease exists, or (B) with agreement from the Principal Investigator (PI), participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible to participate if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low, or (C) with agreement from the PI, other malignancies may be permitted if the risk of the prior malignancy interfering with either safety or efficacy end points is very low. Adequately treated basal or squamous cell carcinoma or carcinoma in situ is allowed.\n* The patient is pregnant or breastfeeding.\n* History of hypersensitivity or contraindication to TTF.\n* Implanted pacemaker, defibrillator or other electrical medical devices.\n* The participant has a previously-identified allergy or hypersensitivity to cabozantinib, nab-paclitaxel, or pembrolizumab, medical adhesives or hydrogel or the patient has received prior cabozantinib and discontinued therapy due to unacceptable toxicity.\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.\n* The patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.\n* CABOZANTINIB COHORT ONLY: The patient has experienced clinically-significant hematemesis or hemoptysis of \\> 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel.\n* CABOZANTINIB COHORT ONLY: The patient has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment.\n* CABOZANTINIB COHORT ONLY: The patient has prothrombin time\u002Finternational normalized ratio (PT\u002FINR) or partial thromboplastin time (PTT) test results that are above (1.3X) the laboratory upper limit of normal.\n* CABOZANTINIB COHORT ONLY: The subject has a corrected QT interval (QTcF) \\> 450 ms for men or \\> 470 ms for women.\n* CABOZANTINIB COHORT ONLY: The patient requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents. Low-dose aspirin (≤ 81 mg\u002Fday), low dose warfarin (≤ 1mg\u002Fday), and prophylactic low molecular weight heparin (LMWH) are permitted.\n* CABOZANTINIB COHORT ONLY: Patients with encasement of a major artery or bowel by tumor are excluded.\n* CABOZANTINIB COHORT ONLY: The patient is unable to swallow capsules.\n* CABOZANTINIB COHORT ONLY: History of hypersensitivity or contraindication to cabozantinib.\n* ATEZOLIZUMAB-CONTAINING COHORT: Participants who have received prior immunotherapy, including prior anti-PD-1 or anti-PD-L1 therapies may participate: (A) only if their prior anti-PD-1 or anti-PDL1 monotherapy or combination therapy were NOT the last treatment prior to participation on this study. (B) Participants who had prior immunotherapies and experienced Grade 1-2 immune-related adverse event (irAE) must have documentation that their irAEs are Grade 1 or 0 using current Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and participants must be off steroid therapy and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 14 days from Cycle 1, Day 1. (C) Participants who experienced Grade 3 irAEs consisting of laboratory abnormalities that were asymptomatic and have now resolved to Grade 1 or 0 and participants who have been off steroid and\u002For other immunosuppressive therapy, as treatment for irAEs, for \\>= 30 days from Cycle 1, Day 1. Participants with prior irAE pneumonitis (\\>= Grade 2) should not be given atezolizumab.\n* ATEZOLIZUMAB-CONTAINING COHORT: Human immunodeficiency virus (HIV) infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics.\n* ATEZOLIZUMAB-CONTAINING COHORT: Has received a live vaccine within 30 days prior to first dose.\n* ATEZOLIZUMAB-CONTAINING COHORT: Active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.\n* ATEZOLIZUMAB-CONTAINING COHORT: Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g. Wegener's Granulomatosis) are excluded from this study.\n* ATEZOLIZUMAB-CONTAINING COHORT: History of\u002For current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.",{"count":358,"type":20},43,[23],"This phase Ib trial tests the safety, side effects, and best dose of tumor treating fields therapy in combination with either cabozantinib or nab-paclitaxel and atezolizumab in treating patients with solid tumors involving the abdomen or thorax that have spread to other parts of the body (advanced). Tumor treating fields therapy on this study utilizes NovoTTF systems that are wearable devices that use electrical fields at different frequencies that may help stop the growth of tumor cells by interrupting cancer cells' ability to divide. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tumor treating fields therapy in combination with either cabozantinib, or with nab-paclitaxel and atezolizumab may help control advanced solid tumors involving the abdomen or thorax.",[362,363,364,27,365,366,367,368,369,204,80,81,82,83,84,370,371,372,117,373,121,374,375,376,377,378,126,379,380,381,382,383,384,29,385,386,133,387,388,135,389,390,137,391,392,393,394,395,139,396,397,141,398,399,400,143,144,145,401,30,402,403,149,404,405,151,406,407,153,408,155,409,410,157],"Advanced Breast Carcinoma","Advanced Endometrial Carcinoma","Advanced Fallopian Tube Carcinoma","Advanced Malignant Abdominal Neoplasm","Advanced Malignant Female Reproductive System Neoplasm","Advanced Malignant Thoracic Neoplasm","Advanced Ovarian Carcinoma","Advanced Primary Peritoneal Carcinoma","Malignant Abdominal Neoplasm","Malignant Solid Neoplasm","Metastatic Breast Carcinoma","Metastatic Fallopian Tube Carcinoma","Metastatic Malignant Abdominal Neoplasm","Metastatic Malignant Female Reproductive System Neoplasm","Metastatic Malignant Thoracic Neoplasm","Metastatic Ovarian Carcinoma","Metastatic Primary Peritoneal Carcinoma","Prognostic Stage III Breast Cancer AJCC v8","Prognostic Stage IIIA Breast Cancer AJCC v8","Prognostic Stage IIIB Breast Cancer AJCC v8","Prognostic Stage IIIC Breast Cancer AJCC v8","Prognostic Stage IV Breast Cancer AJCC v8","Stage III Fallopian Tube Cancer AJCC v8","Stage III Ovarian Cancer AJCC v8","Stage III Primary Peritoneal Cancer AJCC v8","Stage III Uterine Corpus Cancer AJCC v8","Stage IIIA Fallopian Tube Cancer AJCC v8","Stage IIIA Ovarian Cancer AJCC v8","Stage IIIA Primary Peritoneal Cancer AJCC v8","Stage IIIA1 Fallopian Tube Cancer AJCC v8","Stage IIIA1 Ovarian Cancer AJCC v8","Stage IIIA2 Fallopian Tube Cancer AJCC v8","Stage IIIA2 Ovarian Cancer AJCC v8","Stage IIIB Fallopian Tube Cancer AJCC v8","Stage IIIB Ovarian Cancer AJCC v8","Stage IIIB Primary Peritoneal Cancer AJCC v8","Stage IIIC Fallopian Tube Cancer AJCC v8","Stage IIIC Ovarian Cancer AJCC v8","Stage IIIC Primary Peritoneal Cancer AJCC v8","Stage IV Fallopian Tube Cancer AJCC v8","Stage IV Ovarian Cancer AJCC v8","Stage IV Primary Peritoneal Cancer AJCC v8","Stage IV Uterine Corpus Cancer AJCC v8","Stage IVA Fallopian Tube Cancer AJCC v8","Stage IVA Ovarian Cancer AJCC v8","Stage IVA Primary Peritoneal Cancer AJCC v8","Stage IVB Fallopian Tube Cancer AJCC v8","Stage IVB Ovarian Cancer AJCC v8","Stage IVB Primary Peritoneal Cancer AJCC v8","2026-01-13",{"date":413,"type":35},"2026-01-14",{"date":415,"type":35},"2022-04-29",{"date":417,"type":20},"2026-09-01",{"name":329,"class":42},{"id":420,"slug":421,"hasResults":11,"nctId":422,"briefTitle":423,"officialTitle":424,"acronym":4,"eligibilityCriteria":425,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":426,"targetDuration":4,"studyType":21,"phases":428,"briefSummary":429,"conditions":430,"keywords":431,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":433,"lastUpdatePostDateStruct":434,"startDateStruct":436,"completionDateStruct":438,"leadSponsor":440,"locationsCount":43},"100395542","phase-2-durvalumab-withwithout-tremelimumab-after-palliative-hypofractionated-radiotherapy-for-hepatocellular-carcinoma-100395542","NCT04430452","Durvalumab With\u002FWithout Tremelimumab After Palliative Hypofractionated Radiotherapy for Hepatocellular Carcinoma","Phase II Trial of Durvalumab (MEDI4736) With\u002FWithout Tremelimumab for Advanced Hepatocellular Carcinoma After Palliative Hypofractionated Radiotherapy","Inclusion Criteria:\n\n1. Histologically-diagnosed HCC with progression during or after prior PD-(L)1 checkpoint inhibitor immunotherapy (e.g., nivolumab and\u002For pembrolizumab or atezolizumab; prior durvalumab excluded), or without prior PD-(L)1 checkpoint inhibitor immunotherapy.\n\n   a. For patients without prior histologic or cytologic diagnosis, radiographic diagnosis is allowed provided patients meet American Association for the Study of Liver Diseases (AASLD) criteria for radiographic diagnosis.\n2. At least 1 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-measurable tumor present which has not received RT or other local therapy prior to enrollment.\n3. Clinical indication for RT to any site (e.g. painful primary or metastatic tumor, local complication risk such as impending biliary or vascular obstruction).\n4. Child Pugh score of A, B7, or B8 provided other liver function criteria are met.\n5. Eastern Cooperative Oncology Group (ECOG) 0 or 1\n6. Appropriate antiviral therapy for hepatitis B virus (HBV) according to institutional standard of care with HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) \\\u003C 2000 IU\u002FmL.\n7. Adequate organ function as defined below:\n\n   * Hemoglobin \\>= 9.0 g\u002FdL\n   * Absolute neutrophil count \\>= 1,200\u002Fmicroliter (mcL)\n   * Platelet count \\>= 60,000\u002FmcL\n   * Serum bilirubin =\\\u003C 1.5 x institutional upper limit of normal. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician\n   * Aspartate aminotransferase (AST) =\\\u003C 2.5 x institutional upper limit of normal unless liver metastases are present in which case it can be =\\\u003C 5 x upper limit of normal (ULN)\n   * International normalized ratio (INR) \\\u003C 1.5\n   * Creatinine clearance \\> 30 mL\u002Fmin by Cockcroft Gault formula.\n8. No contraindication to immune checkpoint inhibitor immunotherapy.\n9. No contraindication to RT.\n10. Age \\>=18 years at time of study entry.\n11. Life expectancy of \\>= 12 weeks.\n12. Body weight \\> 30 kg (66.1 pounds).\n13. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:\n\n    * Women \\\u003C 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)\n    * Women \\>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \\> 1 year ago, had chemotherapy-induced menopause with last menses \\> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)\n14. Women of childbearing potential and men must agree to use adequate contraception from the time of screening through the duration of study participation and for at least 6 months after receiving combination of durvalumab plus tremelimumab and 3 months after last dose of durvalumab.\n15. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n16. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the United States (US) obtained from the patient\u002Flegal representative prior to performing any protocol-related procedures, including screening evaluations.\n\nExclusion Criteria:\n\n1. Prior radiotherapy to tumor sites requiring RT which could compromise safety of additional treatments.\n2. Prior radiotherapy to more than 30% of bone marrow or to a wide field within 4 weeks of the first study treatment.\n3. Prior treatment with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or PD-L1 inhibitor.\n4. History of allogenic organ transplantation.\n5. On prior PD-1 inhibitor immunotherapy:\n\n   * Any immune-related adverse events with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 grade \\>= 3 on any prior immunotherapy or toxicity that led to permanent discontinuation of prior immunotherapy.\n   * Any AEs while receiving prior immunotherapy not resolved to grade =\\\u003C 1 or resolved to baseline, with the exception of patients with endocrine AE of grade =\\\u003C 2, who are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic\n   * Required the use of additional immunosuppression other than corticosteroids for the management of an AE, experienced recurrence of a grade \\>= 3 AE if previously re-challenged, and currently require maintenance doses of \\> 10 mg prednisone or equivalent per day\n6. Major surgery, liver-directed therapy, or any other anticancer therapy (e.g. chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) less than 4 weeks prior to enrollment\n7. Any other unresolved toxicity NCI CTCAE grade \\>= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.\n\n   * Patients with grade \\>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician\n   * Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician\n8. Concurrent enrollment in another interventional clinical study, except only in the follow-up period of that study.\n9. Participation in another interventional clinical study with an investigational product during the past 4 weeks except only in the follow-up period of that study.\n10. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[e.g., colitis or Crohn's disease\\], diverticulitis \\[with the exception of diverticulosis\\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\\]). The following are exceptions to this criterion:\n\n    * Patients with vitiligo or alopecia\n    * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement\n    * Any chronic skin condition that does not require systemic therapy\n    * Patients with celiac disease controlled by diet alone\n    * Patients without active disease in the last 5 years may be included but only after consultation with the study physician\n11. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent\n12. History of another primary malignancy except for:\n\n    * Malignancy treated with curative intent and with no known active disease \\>= 2 years before the first dose of investigational product (IP) and of low potential risk for recurrence\n    * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease\n    * Adequately treated carcinoma in situ without evidence of disease\n13. History of leptomeningeal carcinomatosis.\n14. History of active primary immunodeficiency.\n15. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice).\n16. Known human immunodeficiency virus (HIV) infection.\n17. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab\u002Ftremelimumab. The following are exceptions to this criterion:\n\n    * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)\n    * Systemic corticosteroids at physiologic doses not to exceed 10 mg\u002Fday of prednisone or its equivalent\n    * Steroids as premedication for hypersensitivity reactions (e.g., computed tomography \\[CT\\] scan premedication)\n18. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.\n19. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening through the duration of study participation and for at least 6 months after receiving combination of durvalumab plus tremelimumab and 3 months after last dose of durvalumab.\n20. Known allergy or hypersensitivity to IP, any of the study drugs, or any of the study drug excipients.\n21. Prior randomization or treatment in a previous durvalumab and\u002For tremelimumab clinical study regardless of treatment arm assignment.\n22. Involvement in the planning and\u002For conduct of the study (applies to both AstraZeneca staff and\u002For staff at the study site).\n23. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.",{"count":427,"type":20},21,[24],"This phase II trial studies how well standard of care hypofractionated radiation therapy followed by durvalumab with or without tremelimumab works in treating patients with hepatocellular cancer (liver cancer) that has spread to other places in the body (advanced) and that is growing, spreading, or getting worse (progressing). In some patients, cancer cells and immune cells start to express signals that stop the body's immune system from killing the cancer. New drugs being developed, such as durvalumab and tremelimumab, are designed to target and block these signals and may help increase the immune response to prevent or slow down cancer growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may help the immune system work even better. Giving durvalumab with or without tremelimumab after radiation therapy may work better than radiation therapy alone in treating patients with liver cancer.",[27,29,135,139,30,151,155],[432],"Immunotherapy","2025-12-01",{"date":435,"type":35},"2025-12-08",{"date":437,"type":35},"2022-02-04",{"date":439,"type":20},"2029-07-31",{"name":441,"class":42},"Mary Feng, MD",{"id":443,"slug":444,"hasResults":11,"nctId":445,"briefTitle":446,"officialTitle":447,"acronym":4,"eligibilityCriteria":448,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":449,"targetDuration":4,"studyType":21,"phases":451,"briefSummary":452,"conditions":453,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":454,"lastUpdatePostDateStruct":455,"startDateStruct":457,"completionDateStruct":459,"leadSponsor":461,"locationsCount":463},"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":450,"type":20},122,[24],"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.",[102,121,29,135,139,30,151,155,164],"2025-09-10",{"date":456,"type":35},"2025-09-16",{"date":458,"type":35},"2022-05-27",{"date":460,"type":20},"2026-12-31",{"name":462,"class":42},"Academic and Community Cancer Research United",16]