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

Обзор

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.

Подробное описание

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.

Вмешательства

• Лучевая терапия 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

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: Three years]

Вторичные конечные точки (4)

• Overall survival [Срок оценки: Three years]
• intrahepatic tumor response [Срок оценки: Three years]
• rate of achieving curative down-staging [Срок оценки: Three years]
• treatment-related toxicity [Срок оценки: Three years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• Yonsei University Health System, Severance Hospital — Seoul

Идентификаторы

NCT: NCT07246668 · 4-2025-0048

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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