Atezolizumab and Bevacizumab With Combined Radiotherapy for Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Atezolizumab plus Bevacizumab combination therapy (AtezoBev) is well-known 1st-line therapy for advanced hepatocellular carcinoma (HCC). However, there are unmet needs for patients with advanced HCC who do not respond to AtezoBev. External beam radiotherapy (RT) is another well-known locoregional therapy for HCC that induces inflammatory cascade and abscopal effect as a systemic anticancer effect and enhances the effect of AtezoBev. Therefore, the investigators aim to verify the effect of AtezoBev plus RT for advanced HCC through this single-center, prospective phase II one-armed cohort study over three years. This study recruits 51 patients to verify the effect of the intervention. Atezolizumab (1200mg) and Bevacizumab (15mg/kg) are administered to patients once for each cycle at 3-week intervals, and additional radiotherapy for the mass or portal vein tumor thrombosis is performed before second cycle of AtezoBev. The primary endpoint is progression-free survival by using response evaluation with modified RECIST.

Official Title
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A Single-arm Phase II Trial of Atezolizumab and Bevacizumab With Combined Radiotherapy in Advanced Hepatocellular Carcinoma With Portal Vein Invasion

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: AtezoBev with combined radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥19; clinically or histologically diagnosed HCC; HCC with Vp2-Vp4 portal vein invasion; intact liver function with Child-Pugh class A; adequate size of RT field; intact performance with ECOG below 2; non-pregnant with acceptable contraception in premenopausal women); without other life-threatening diseases; ability to provide written informed consent and to comply with all study conditions. Exclusion Criteria: Active uncontrolled infection; Current or history (< or = 5 years) of advanced malignancies in the other organs; History of liver transplantation; miliary HCC which incompatible external beam RT

Ages Eligible for Study
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Minimum Age: 19 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: Therapeutic arm<br>AtezoBev with combined radiotherapy | Drug: AtezoBev with combined radiotherapy<br>* Atezolizumab (1200mg) and Bevacizumab (15mg/kg) are administered to patients once for each cycle with 3-week intervals, and additional radiotherapy (iGTV 50-60 Gy, CTV 40Gy, PTV 30Gy / 10Fx) for the mass or portal vein tumor thrombosis is performed before second cycle of AtezoBev.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Duration between AtezoBev initiation and tumor progression by mRECIST or patient's death | 2 years (per 9 weeks) |