Systemic Therapy Combined With Stereotactic Body Radiotherapy Versus Systemic Therapy Alone in BCLC Stage C Hepatocellular Carcinoma (SCRATCH): A Prospective, Multicenter, Phase II, Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 184
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This prospective, multicenter, phase II randomized controlled trial compares the efficacy and safety of SBRT combined with systemic therapy versus systemic therapy alone in BCLC stage C hepatocellular carcinoma (HCC). The primary objective is to compare overall survival (OS) between the two arms. Secondary objectives include progression-free survival (PFS), objective response rate (ORR), quality of life (QoL), and incidence and severity of adverse events (AEs). Eligible patients will be randomized 2:1 to an experimental arm (SBRT + systemic therapy) or control arm (systemic therapy alone). Key inclusion criteria include BCLC C disease, Child-Pugh A-B liver function, ECOG ≤2, measurable disease per RECIST 1.1, and stable intrahepatic disease after initial systemic therapy for ≥3 months when applicable. The trial will also include predefined safety monitoring, QoL assessments (EORTC QLQ-C30 and QLQ-HCC18), and exploratory biomarker analyses.
详细描述
Background: Hepatocellular carcinoma (HCC) is frequently diagnosed at advanced stages with limited curative options. Systemic therapies (targeted agents and immune checkpoint inhibitors) have improved outcomes in BCLC C patients, but their therapeutic effect is unsatisfactory. SBRT provides precise high-dose local control and may synergize with systemic therapy by enhancing tumor immunogenicity and improving local disease control.
Study design: Prospective, randomized, open-label, multicenter Phase II trial. In the experimental arm, patients will continue the guideline-recommended systemic treatment received prior to enrollment, in accordance with approved labels and national guidelines, combined with SBRT delivered to portal vein tumor thrombus (PVTT, if present) and/or limited extrahepatic metastatic lesions. In the control arm, patients will continue the same guideline-recommended systemic treatment without SBRT.
Endpoints: The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), objective response rate (ORR by RECIST 1.1 and mRECIST), disease control rate (DCR), duration of response (DoR), quality of life (EORTC QLQ-C30 and QLQ-HCC18), and safety (CTCAE v5.0). Exploratory endpoints may include biomarker dynamics (e.g., immune cell infiltration, viral markers) and patterns of progression.
Safety and monitoring: AEs will be collected from consent through 30 days after the last radiotherapy; SAEs will be reported per protocol (including deaths up to 90 days after radiotherapy). Regular imaging and clinical assessments will monitor efficacy and safety. Data management and monitoring will follow GCP.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-70 years.
- •Histologically or clinically diagnosed HCC per national guidelines.
- •BCLC stage C (CNLC IIIA/IIIB), including PVTT and/or extrahepatic metastases amenable to protocol procedures.
- •Child-Pugh class A or B (score ≤7).
- •At least one measurable lesion per RECIST 1.1 (criteria specified).
- •Expected survival ≥6 months.
- •Adequate organ function per protocol thresholds.
- •For experimental arm candidates: active lesion count (when PET-CT used) ≤
- •If prior initial systemic therapy given: intrahepatic disease stable ≥3 months.
- •Effective contraception from consent through 1 year after treatment end.
- •Ability to understand and sign consent.
排除标准
- •Second primary malignancy (exceptions apply).
- •Tumor thrombus/metastases judged not amenable to radiotherapy.
- •Prior systemic anticancer therapy for current HCC (prior local therapy permitted per rules).
- •Severe organ dysfunction precluding treatment.
- •Uncontrolled comorbidities (e.g., uncontrolled diabetes, active peptic ulcer, severe cardiopulmonary disease).
- •Active uncontrolled infection or active autoimmune disease requiring systemic therapy.
- •Significant neurologic dysfunction.
- •Pregnant or breastfeeding women; no effective contraception.
- •Known hypersensitivity to planned drugs.
- •Any other condition making participation unsuitable per investigator.
研究组 & 干预措施
Treatment
SBRT + Systemic Therapy
干预措施: Systemic therapy (Drug)
Control
Systemic therapy will consist of the continuation of the guideline-recommended systemic treatment received prior to enrollment, in accordance with approved labels and national guidelines.
干预措施: Systemic therapy (Drug)
Treatment
SBRT + Systemic Therapy
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Overall Survival (OS)
时间窗: subjects will be followed up for a minimum combined accrual + follow-up period of 48 months (24-month enrollment + 24-month follow-up planned)
Time from date of randomization to date of death from any cause
次要结局
- Progression-Free Survival (PFS)(2 years)
- Objective Response Rate (ORR)(2 years)
- Disease Control Rate (DCR)(2 years)
- Duration of Response (DoR)(2 years)
- Quality of Life (QoL)(3 years)
- Treatment-Related Adverse Events (AEs)(3 months)
研究者
Jinbo Yue
Director of Department Radiation Oncology
Shandong Cancer Hospital and Institute