Adjuvant Radiotherapy Combined With Sintilimab Versus Transarterial Chemoembolization (TACE) for Hepatocellular Carcinoma With Narrow Margins and High-Risk Features Following Resection: A Multi-center Phase III Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 286
- 试验地点
- 1
- 主要终点
- 2-year RFS
研究概览
简要总结
This study is an open-label, randomized controlled, multicenter, phase III clinical trial
详细描述
This study is an open-label, randomized controlled, multicenter, phase III clinical trial where participants are randomized in a 1:1 ratio to either the experimental or control group. The experimental group will initiate radiotherapy within 4 months postoperatively with prescribed doses of 44-50Gy in 22-25 fractions to the tumor bed and 56-60Gy in 22-25 fractions to narrow-margin areas adjacent to major blood vessels, along with concurrent sintilimab 200mg q3w for 2 cycles followed by maintenance sintilimab 200mg q3w for 15 cycles (approximately 1 year total treatment duration) until disease progression or unacceptable toxicity. The control group will receive the first TACE procedure within 4 months postoperatively, with the decision on administering a second TACE to be determined by the investigator based on the patient's condition and first TACE response assessment. The primary endpoint is 2-year recurrence-free survival (RFS) rate, while secondary endpoints include 2-year overall survival (OS) rate and incidence of adverse events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •R0 resection of hepatocellular carcinoma (HCC) with a surgical margin <1 cm (determined by postoperative pathology, surgical records, and imaging).
- •Within 4 months after curative resection.
- •High-Risk Recurrence Factors (at least one required in addition to narrow margin): (1) Microvascular invasion (MVI) positive, tumor thrombus, or satellite nodules (2) Preoperative AFP >400 ng/mL (3) Tumor >5 cm with incomplete capsule
- •≥18 and ≤80 years old.
- •ECOG score 0-
- •Child-Pugh Class: A5, A6, or B
- •Postoperative Contrast-enhanced MRI of the liver must be performed to exclude intrahepatic residual lesions.
- •HBV DNA and HCV RNA status do not affect eligibility, but if HBV DNA positive and/or HCV RNA positive: ALT must be <1.5× upper limit of normal (ULN). Antiviral therapy must be initiated.
- •Liver Function Tests (LFTs): ALT ≤2.5× ULN (if HBV/HCV positive, ALT ≤1.5× ULN). If ALT ≤1.5× ULN, AST ≤6× ULN (excluding AST elevation due to myocardial infarction). If ALT 1.5-2.5× ULN, AST ≤2.5× ULN.
- •No significant ECG abnormalities and no severe cardiac dysfunction.
- •Serum creatinine (CRE) and BUN ≤2.5× ULN.
- •Hb≥80g/L，ANC≥1.0×109 /L，PLT≥40×109 /L.
- •Written informed consent obtained.
排除标准
- •Vp3 or Vp4 portal vein tumor thrombus (PVTT) or Vv2/Vv3 inferior vena cava (IVC) tumor thrombus on preoperative imaging.
- •Previous anti-HCC therapies, including but not limited to: targeted therapy (e.g., tyrosine kinase inhibitors), immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors) or systemic chemotherapy
- •Distant metastasis before randomization.
- •Moderate to severe ascites unresponsive to medical management.
- •History of other malignancies, except: carcinoma in situ，early-stage papillary thyroid cancer or basal cell carcinoma of the skin
- •Previous radiotherapy involving the abdomen.
- •Significant cardiac, renal, or other major organ dysfunction.
- •Active Autoimmune Disease or Psychiatric Disorders.
- •HIV Infection.
- •Pregnant or breastfeeding women.
- •Currently enrolled in another interventional clinical trial.
研究组 & 干预措施
control group
The control group will receive the first TACE procedure within 4 months postoperatively, with the decision on administering a second TACE to be determined by the investigator based on the patient's condition and first TACE response assessment.
干预措施: TACE (Procedure)
experiment group
The experimental group will initiate radiotherapy within 4 months postoperatively with prescribed doses of 44-50Gy in 22-25 fractions to the tumor bed and 56-60Gy in 22-25 fractions to narrow-margin areas adjacent to major blood vessels, along with concurrent sintilimab 200mg q3w for 2 cycles followed by maintenance sintilimab 200mg q3w for 15 cycles (approximately 1 year total treatment duration) until disease progression or unacceptable toxicity.
干预措施: Sintilimab (Drug)
experiment group
The experimental group will initiate radiotherapy within 4 months postoperatively with prescribed doses of 44-50Gy in 22-25 fractions to the tumor bed and 56-60Gy in 22-25 fractions to narrow-margin areas adjacent to major blood vessels, along with concurrent sintilimab 200mg q3w for 2 cycles followed by maintenance sintilimab 200mg q3w for 15 cycles (approximately 1 year total treatment duration) until disease progression or unacceptable toxicity.
干预措施: radiotherapy (Radiation)
结局指标
主要结局
2-year RFS
时间窗: 2-year after randomization
the percentage of patients who remain free of detectable cancer recurrence (local, regional, or distant) and alive for at least 2 years after randomization
次要结局
- 2-year OS(2-year after randomization)
- adverse events(up to 2 years after randomization)