A Phase II Single-Arm Clinical Study to Evaluate the Efficacy and Safety of Carbon Ion Radiotherapy With Atezolizumab and Bevacizumab Combination Therapy in Patients With Advanced Hepatocellular Carcinoma

NCT ID: NCT07246668

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-10
• Study Completion Date: 2028-03-31

Brief Summary

This single-center, prospective phase II clinical trial evaluates the safety and therapeutic efficacy of combining carbon ion radiotherapy with the standard first-line regimen of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma. The study aims to determine whether the addition of carbon ion radiotherapy enhances tumor control and improves clinical outcomes beyond those achieved with systemic therapy alone. Key endpoints include overall survival, progression-free survival, objective response rate, and treatment-related adverse events.

Detailed Description

This clinical trial aims to determine whether adding carbon ion radiotherapy to atezolizumab-bevacizumab therapy improves tumor control and enhances immune response in patients with advanced hepatocellular carcinoma. Over a 3-year study period, eligible patients receiving atezolizumab and bevacizumab who are also suitable for carbon ion radiotherapy will undergo the combined treatment. Clinical outcomes including survival, progression, radiologic response, and toxicity (graded using CTCAE v5.0) will be monitored and assessed.

Conditions

Hepatocellular Carcinoma; Liver Neoplasms; Carcinoma; Hepatocellular

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carbon Ion Radiotherapy + Atezolizumab + Bevacizumab

Participants will receive standard first-line systemic therapy with atezolizumab (1200 mg IV every 3 weeks) plus bevacizumab (15 mg/kg IV every 3 weeks). Carbon ion radiotherapy will be integrated as a sequential local treatment during the early phase of systemic therapy.

Carbon ion radiotherapy will be delivered to the primary hepatic tumor using a hypofractionated regimen (approximately 4-12 fractions), with dose and fractionation individualized according to tumor extent, anatomical proximity to gastrointestinal organs, and institutional organ-at-risk constraints.

Following completion of carbon ion radiotherapy, participants will continue atezolizumab-bevacizumab maintenance therapy until radiologic disease progression, unacceptable toxicity, or withdrawal of consent. This protocol is designed to enhance local tumor control while preserving the systemic therapeutic benefit of atezolizumab and bevacizumab.

Group Type: EXPERIMENTAL

Carbon Ion Radiotherapy Atezolizumab Bevacizumab

Intervention Type: RADIATION

Participants will initiate systemic therapy with atezolizumab (1200 mg IV every 3 weeks) and bevacizumab (15 mg/kg IV every 3 weeks). Carbon ion radiotherapy will subsequently be administered to the primary hepatic lesion during the early phase of systemic therapy.

Carbon ion radiotherapy will be delivered using a hypofractionated schedule (approximately 4-12 fractions), with dose and fractionation individualized based on tumor size, anatomical location, and organ-at-risk considerations. After completion of carbon ion radiotherapy, participants will continue maintenance treatment with atezolizumab and bevacizumab until disease progression or unacceptable toxicity.

Interventions

Carbon Ion Radiotherapy Atezolizumab Bevacizumab

Participants will initiate systemic therapy with atezolizumab (1200 mg IV every 3 weeks) and bevacizumab (15 mg/kg IV every 3 weeks). Carbon ion radiotherapy will subsequently be administered to the primary hepatic lesion during the early phase of systemic therapy.

Carbon ion radiotherapy will be delivered using a hypofractionated schedule (approximately 4-12 fractions), with dose and fractionation individualized based on tumor size, anatomical location, and organ-at-risk considerations. After completion of carbon ion radiotherapy, participants will continue maintenance treatment with atezolizumab and bevacizumab until disease progression or unacceptable toxicity.

Intervention Type: RADIATION

Other Intervention Names

Atezolizumab: Anti-PD-L1 antibody Bevacizumab: Anti-VEGF monoclonal antibody Carbon Ion Radiotherapy: Heavy-ion radiotherapy, C-ion RT

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years Histologically or radiologically confirmed hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage B or C, not eligible for curative surgery or transplantation.

At least one measurable lesion according to RECIST criteria. Eligible for treatment with atezolizumab plus bevacizumab based on clinical judgment.

Candidate for carbon ion radiotherapy determined by radiation oncologist. Child-Pugh class A liver function Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Adequate organ and marrow function, including:

Absolute neutrophil count ≥ 1,500/μL Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min AST/ALT ≤ 5 × ULN Total bilirubin ≤ 3 mg/dL No uncontrolled esophageal or gastric varices, confirmed by endoscopy (within 6 months), or adequately treated before enrollment.

Ability to understand and willingness to sign a written informed consent form.

Exclusion Criteria

• Prior systemic therapy with anti-PD-1, anti-PD-L1, or anti-VEGF agents within the past year.

Prior carbon ion radiotherapy to the same anatomical region.

Presence of uncontrolled or severe cardiovascular disease, including:

Recent myocardial infarction (within 6 months) Uncontrolled hypertension NYHA class III-IV heart failure Active or history of autoimmune disease requiring systemic immunosuppressive therapy.

Active infection, including:

Uncontrolled bacterial, viral, or fungal infection Active tuberculosis HIV infection, or active hepatitis B/C with uncontrolled viral replication.

Significant bleeding risk, including:

Active gastrointestinal bleeding Untreated or high-risk varices Coagulopathy not controllable with standard therapy Portal vein tumor thrombosis (PVTT) of grade Vp4 if judged unsuitable for treatment by investigator.

Pregnant or breastfeeding women History of organ transplantation, including liver transplantation. Any condition judged by the investigator to interfere with study participation, treatment compliance, or safety evaluation.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yonsei University Health System, Severance Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Facility Contacts

Ik Jae Lee

Role: primary

IKJAE412@YUHS.AC

+82-2-2228-8117

Other Identifiers

4-2025-0048

Identifier Type: -

Identifier Source: org_study_id