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
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.
• 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