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

NCT07246668 | Recruiting Phase 2

• 1 other identifier: 4-2025-0048
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma; Liver Neoplasms; Carcinoma; Hepatocellular

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival is defined as the time from the first administration of atezolizumab plus bevacizumab to the date of documented tumor progression or death from any cause, whichever occurs first.

  Three years

Secondary Outcomes (4)

• Overall survival

  Three years

• intrahepatic tumor response

  Three years

• rate of achieving curative down-staging

  Three years

• treatment-related toxicity

  Three years

Study Arms (1)

Carbon Ion Radiotherapy + Atezolizumab + Bevacizumab

EXPERIMENTAL

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.

Radiation: Carbon Ion Radiotherapy Atezolizumab Bevacizumab

Interventions

Carbon Ion Radiotherapy Atezolizumab Bevacizumab 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.

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

Carbon Ion Radiotherapy + Atezolizumab + Bevacizumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms; Carcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study; no masking will be applied.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is designed as a single-group, open-label, prospective phase II trial evaluating the combination of carbon ion radiotherapy with atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: March 10, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)