SBRT With Atezo/Bev for HCC

Study Overview
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Brief Summary
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A phase I dose escalation and pharmacodynamic study of repeated dose stereotactic body radiotherapy (SBRT) administered with concurrent atezolizumab and bevacizumab for patients with advanced hepatocellular carcinoma (HCC)

Official Title
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A Phase I Study of SBRT Vaccination With Atezolizumab and Bevacizumab for Patients With Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: SBRT + atezolizumab and bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have hepatocellular carcinoma (HCC) that is not amenable to curative-intent surgical or ablation (where surgery or ablation are not indicated due to disease extent, co-morbidities, or other technical reasons) and systemic therapy is indicated. Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study treatment plan<br>Patients will be enrolled in a Rolling 6 clinical trial design1. This study design retains sensitivity to identifying DLTs while having the benefit of decreasing accrual time given the long DLT period required to assess radiation toxicity. In this trial design, up to 6 patients can be enrolled at a time onto a dose level while awaiting DLT assessment. Established rules guide the decision for enrolling onto the current, next highest, or previous dose level based on the number of participants currently enrolled in a given cohort, the number of radiation-attributable dose-limiting toxicities (ra-DLTs) observed, and the number of patients with immature toxicity data. If the MTD is not reached after 6 patients have enrolled on dose level 3 (three 17Gy fractions of SBRT) and have completed toxicity evaluations, then the recommended phase 2 dose will be determined based on an analysis of the efficacy of the combination | Biological: SBRT + atezolizumab and bevacizumab<br>* Stereotactic Body Radiotherapy (SBRT) is a radiation procedure that delivers precise doses of radiation in fractions. See following section for more information on the schedule, dose, volume, and simulation of SBRT. Atezolizumab is an FDA-approved immune checkpoint inhibitor that is used in the treatment of advanced HCC. It is administered as a flat-dose 1200 mg intravenous infusion every three weeks. Bevacizumab is an FDA-approved anti-VEGF monoclonal antibody that is used in the treatment of advanced HCC in combination with atezolizumab. It is administered as a weight-based dose of 15 mg/kg intravenous infusion every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Objective | we will measure the total number of subjects that can tolerate the recommended phase II regimen of SBRT with atezolizumab/bevacizumab (atezo/bev) in patients with advanced hepatocellular carcinoma and the proportion of patients experiencing a radiation-attributable DLT at each dose level. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Objective | To assess efficacy and safety, in terms of tumor objective response rate (ORR) by RECIST 1.1 and iRECIST | 3 years | 
| Overall Survival | we will be measuring for Overall Survival (OS) post study treatment. | 5 years | 
| Progression Free survival | We will be measuring for progression free survival with RECIST 1.1 definition | 5 years |