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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study; no masking will be applied.
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Carbon Ion Radiotherapy Atezolizumab Bevacizumab (Radiation)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Three years
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.
次要结局
- Overall survival(Three years)
- intrahepatic tumor response(Three years)
- rate of achieving curative down-staging(Three years)
- treatment-related toxicity(Three years)