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.
Participant must provide written informed consent before any study-specific procedures or interventions are performed
Participants aged ≥ 18 years
Body weight > 30 kg
Barcelona Clinic Liver Cancer Stage B or C
Another primary tumor
Extrahepatic metastases
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
Note: Eligible participants must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
Single group
Angiogram
Procedure/SurgeryUndergo angiogram
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood and urine sample collection
Computed Tomography
Procedure/SurgeryUndergo CT scan
Durvalumab
Biological/VaccineGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Single Photon Emission Computed Tomography
Procedure/SurgeryUndergo SPECT
Tremelimumab
Biological/VaccineGiven IV
Yttrium-90 Microsphere Radioembolization
Procedure/SurgeryGiven via transartieral radioembolization procedure
Zanzalintinib
DrugGiven PO
Proportion of progression-free at 6-months
Will be reported with 95% exact confidence interval.
Incidence of grade ≥ 3 adverse events (AEs)
Assessed per Common Terminology Criteria for Adverse Events version 5.0. The 95% confidence interval will be reported with the point estimate of toxicity rate.
Objective response rate
Defined as the proportion of participants that achieve a best overall response of complete response (CR) or partial response (PR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Will be reported with 95% exact confidence interval.
Disease control rate
Defined as the proportion of participants that achieve a best overall response of CR, PR, or stable disease (≥ 6 months, per mRECIST) without evidence of radiologic progression prior to this point. Will be reported with 95% exact confidence interval.
Time to progression (TTP)
Assessed per mRECIST. Will be characterized using the Kaplan-Meier method. Kaplan-Meier curves of TTP will be presented. Median TTP, quartiles and progression rate after specific time points (for example, after 6 and 12 months on treatment) will be estimated from the survival curves. All these parameter estimates will be reported together with their 95% confidence intervals.
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OHSU Knight Cancer Institute
Lead sponsor
Oregon Health and Science University
Collaborator
Exelixis
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
