RecruitingPhase 2NCT06133062

Atezolizumab and Bevacizumab With Proton Radiotherapy for Unresectable Hepatocellular Carcinoma

Investigation of Antitumor Immune Response in Patients With Unresectable Hepatocellular Carcinoma Undergoing Proton Radiotherapy Combined With Atezolizumab and Bevacizumab

Sponsor

Chang Gung Memorial Hospital

Enrollment

45 participants

Start Date

Nov 16, 2023

Study Type

INTERVENTIONAL

Conditions

Hepatocellular Carcinoma Non-resectable

Summary

Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an improved objective response rate (ORR) of 27%, the majority of patients face HCC progression and liver failure \[Finn et al., N Engl J Med 2020\]. Developing a new combined treatment strategy to overcome resistance to anti-PD-L1 and anti-VEGF is essential to improve patient outcomes. Radiation treatment (RT) is notably effective in managing localized solid tumors and is a fundamental component of unresectable HCC treatment. Recent retrospective cohorts have demonstrated that proton RT targeting all hepatic tumors, along with PD-L1/programmed death-1 (PD-1) blockade, enhances ORR and progression-free survival for unresectable HCC patients, displaying a favorable safety profile (Su et al., Am J Cancer Res. 2022). Our preclinical study (Hsieh et al., Sci Immunol 2022) showcased that RT combined with PD-L1/PD-1 blockade stimulates immunogenic cell death and antigen cross-presentation in murine tumor models, promoting systemic antitumor T cell responses. Nonetheless, it is crucial to verify whether the combined therapy of proton RT, atezolizumab, and bevacizumab triggers synergistic antitumor effects and systemic immune activation in clinical trials for unresectable HCC. This phase II non-randomized trial aims to prospectively evaluate therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with atezolizumab/bevacizumab combined with proton radiotherapy.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This trial tests whether combining two immunotherapy drugs (atezolizumab and bevacizumab) with proton beam radiation can improve outcomes for people with liver cancer (hepatocellular carcinoma, or HCC) that cannot be surgically removed. Proton radiation is more precise than standard radiation and may cause less damage to surrounding healthy liver tissue. **You may be eligible if...** - You are 18 or older with liver cancer that cannot be surgically removed or transplanted - Your cancer is at an intermediate or advanced stage (Barcelona stage B or C) - Your liver function is adequate (Child-Pugh score 5-6) - You have not had prior solid organ transplant or autoimmune disease **You may NOT be eligible if...** - You have cirrhosis with significant fluid buildup (ascites) - You have had radioembolization (SIRT) to the liver previously - You have active hepatitis B or C - You have an autoimmune condition such as lupus, rheumatoid arthritis, or inflammatory bowel disease - You are pregnant or unable to use contraception - You have known HIV infection Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGAtezolizumab

Atezolizumab 1200 mg will be administered as an IV infusion on Day 1 of each cycle, with cycles occurring every 3 weeks. The initial dose will be delivered over 60 (± 15) minutes, and if well-tolerated, subsequent infusions may be given over 30 minutes. For patients who achieve a complete response (CR) within one year of treatment, atezolizumab should be continuously used for a year. For patients who experience a partial response (PR), atezolizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive atezolizumab for 6 months. In the case of PD, atezolizumab should be discontinued at the time when PD is confirmed.

DRUGBevacizumab

Bevacizumab 15 mg/kg will be administered as an IV infusion on Day 1 of each 3-week cycle. The initial dose will be delivered over 90 minutes (±15 minutes), and if well-tolerated, subsequent infusions may be given over 60 minutes. For patients who achieve a complete response (CR) within one year of treatment, bevacizumab should be continuously used for a year. In the case of patients experiencing a partial response (PR), bevacizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive bevacizumab for 6 months. In the event of PD, bevacizumab should be discontinued when PD is confirmed. Temporary withholding or dose reduction of bevacizumab is permitted if patients experience adverse events such as bleeding episodes, severe hypertension, or proteinuria at the discretion of the treating physician.

RADIATIONProton radiotherapy

* 72.6 CGE in 22 fractions for tumors ≤1 cm from the hepatic hilum, bowel, and heart. * 66 CGE in 10 fractions for tumors \>1 cm from the hepatic hilum, bowel, and heart.