Efficacy and Safety of PD-L1 Antibody Combined With Bevacizumab and Hepatic Arterial Infusion Chemotherapy in Advanced Unresectable Hepatocellular Carcinoma With Extrahepatic Metastases: A Single-Arm, Prospective, Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) as Assessed by RECIST v1.1
研究概览
简要总结
This is a single-arm, phase II clinical trial evaluating the safety and efficacy of PD-L1 antibody combined with bevacizumab and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced unresectable hepatocellular carcinoma (HCC) with extrahepatic metastases.
Study Population: Patients with advanced HCC who have:
- Confirmed extrahepatic metastases
- No prior PD-L1 or bevacizumab therapy
- Age 18-75 years
- Child-Pugh A or B7 liver function
- ECOG performance status 0-1
Treatment Regimen:
- PD-L1 antibody: 1200mg every 3 weeks
- Bevacizumab: 15mg/kg every 3 weeks
- HAIC with FOLFOX regimen: Up to 6 cycles
- Treatment continues until disease progression or up to 24 months
Primary Endpoint:
-Objective Response Rate (ORR)
Secondary Endpoints:
- Disease Control Rate (DCR)
- Duration of Response (DOR)
- Progression-free Survival (PFS)
- Overall Survival (OS)
- Safety assessments
- Quality of life measurements
Study Design Details:
- Single-arm study using Simon's two-stage design
- First stage: 27 patients
- Second stage: 9 additional patients if first stage shows efficacy
- Total planned enrollment: 36 patients
- Study duration: October 2024 - July 2027
This study aims to evaluate whether adding HAIC to PD-L1 inhibitor plus bevacizumab immunotherapy can improve outcomes for advanced HCC patients with extrahepatic spread, who currently have limited treatment options. The trial will assess both efficacy and safety of this combination approach.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent Histologically/cytologically confirmed hepatocellular carcinoma (HCC) or clinically diagnosed according to HCC diagnostic criteria Radiologically confirmed extrahepatic metastases with unresectable disease as evaluated by investigators No prior treatment with PD-L1 antibody and/or bevacizumab Age ≥18 and ≤75 years ECOG Performance Status 0-1 Child-Pugh Class A or B7 Able to comply with study protocol requirements At least one measurable or evaluable lesion according to RECIST v1.1
- •Adequate organ and bone marrow function:
- •Absolute neutrophil count ≥1.5×10^9/L Platelet count ≥75×10^9/L Hemoglobin ≥9.0 g/dL Total bilirubin ≤2×ULN ALT and AST ≤5×ULN Serum creatinine ≤1.5×ULN or creatinine clearance ≥50mL/min Urine protein <2+ by dipstick APTT and INR ≤1.5×ULN Normal cardiac enzymes Normal thyroid function or on stable replacement therapy Life expectancy ≥12 weeks Effective contraception for participants of childbearing potential during treatment and for 6 months after last dose
排除标准
- •Severe complications from liver disease (severe bleeding from portal hypertension, infection, hepatic encephalopathy) Prior systemic anti-tumor therapy for HCC Other malignancy within 5 years (except adequately treated non-melanoma skin cancer or carcinoma in situ) Current participation in other interventional clinical trials Systemic treatment with Chinese herbal medicine or immunomodulators within 2 weeks before first dose Active autoimmune disease requiring systemic treatment within 2 years Systemic corticosteroid therapy within 7 days before first dose Prior allogeneic organ transplantation (except corneal) or stem cell transplantation Known allergy to monoclonal antibodies or HAIC components Inadequate recovery from prior treatment toxicities Known HIV infection Untreated active HBV infection (HBsAg positive with HBV-DNA above upper limit of normal) Active HCV infection Live vaccine administration within 30 days before first dose Pregnancy or breastfeeding
- •Serious or uncontrolled systemic diseases including:
- •Significant cardiac arrhythmias or conduction abnormalities Unstable angina or NYHA class ≥2 heart failure Arterial thrombotic events within 6 months Uncontrolled hypertension Active interstitial lung disease Active tuberculosis Active systemic infections Active diverticulitis or GI obstruction Uncontrolled diabetes Significant proteinuria Psychiatric disorders affecting compliance Any condition that could interfere with study participation or interpretation of results
研究组 & 干预措施
PD-L1 Antibody + Bevacizumab + HAIC-FOLFOX
Participants will receive:
-
PD-L1 antibody 1200mg intravenously every 3 weeks
-
Bevacizumab 15mg/kg intravenously every 3 weeks
-
HAIC-FOLFOX regimen (up to 6 cycles) consisting of:
-
Oxaliplatin 130 mg/m² via hepatic arterial infusion over 3 hours
-
Leucovorin 400 mg/m² via hepatic arterial infusion over 2 hours
-
Fluorouracil 400 mg/m² bolus via hepatic arterial infusion at hour 5, followed by 2400 mg/m² continuous hepatic arterial infusion over 46 hours
-
HAIC treatment repeats every 3 weeks for up to 6 cycles After completion of HAIC, participants will continue to receive PD-L1 antibody and bevacizumab until disease progression, unacceptable toxicity, or up to 24 months of treatment. Tumor assessments will be performed every 9 weeks for the first 48 weeks, then every 12 weeks thereafter.
干预措施: PD-L1 antibody (Drug)
PD-L1 Antibody + Bevacizumab + HAIC-FOLFOX
Participants will receive:
-
PD-L1 antibody 1200mg intravenously every 3 weeks
-
Bevacizumab 15mg/kg intravenously every 3 weeks
-
HAIC-FOLFOX regimen (up to 6 cycles) consisting of:
-
Oxaliplatin 130 mg/m² via hepatic arterial infusion over 3 hours
-
Leucovorin 400 mg/m² via hepatic arterial infusion over 2 hours
-
Fluorouracil 400 mg/m² bolus via hepatic arterial infusion at hour 5, followed by 2400 mg/m² continuous hepatic arterial infusion over 46 hours
-
HAIC treatment repeats every 3 weeks for up to 6 cycles After completion of HAIC, participants will continue to receive PD-L1 antibody and bevacizumab until disease progression, unacceptable toxicity, or up to 24 months of treatment. Tumor assessments will be performed every 9 weeks for the first 48 weeks, then every 12 weeks thereafter.
干预措施: Bevacizumab (Drug)
PD-L1 Antibody + Bevacizumab + HAIC-FOLFOX
Participants will receive:
-
PD-L1 antibody 1200mg intravenously every 3 weeks
-
Bevacizumab 15mg/kg intravenously every 3 weeks
-
HAIC-FOLFOX regimen (up to 6 cycles) consisting of:
-
Oxaliplatin 130 mg/m² via hepatic arterial infusion over 3 hours
-
Leucovorin 400 mg/m² via hepatic arterial infusion over 2 hours
-
Fluorouracil 400 mg/m² bolus via hepatic arterial infusion at hour 5, followed by 2400 mg/m² continuous hepatic arterial infusion over 46 hours
-
HAIC treatment repeats every 3 weeks for up to 6 cycles After completion of HAIC, participants will continue to receive PD-L1 antibody and bevacizumab until disease progression, unacceptable toxicity, or up to 24 months of treatment. Tumor assessments will be performed every 9 weeks for the first 48 weeks, then every 12 weeks thereafter.
干预措施: HAIC-FOLFOX (Procedure)
结局指标
主要结局
Objective Response Rate (ORR) as Assessed by RECIST v1.1
时间窗: From first dose until disease progression or up to 24 months of treatment, with tumor assessments performed every 9 weeks for the first 48 weeks and every 12 weeks thereafter.
次要结局
未报告次要终点
研究者
Wentao Wang
Professor
West China Hospital