Hepatic Arterial Infusion or Intravenous Infusion of Adebrelimab, Combined With Bevacizumab and Hepatic Arterial Infusion of FOLFOX Chemotherapy for Advanced Hepatocellular Carcinoma: a Multicenter, Open Label, Randomized Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 76
- 试验地点
- 3
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of Adabrelimab (arterial or intravenous administration) combined with hepatic artery FOLFOX infusion chemotherapy and Bevacizumab as the first-line treatment of advanced stage hepatocellular carcinoma. Patients will be randomized 1:1 etither to receive hepatic arterial infusion(HAI) Adabrelimab group or IV Adabrelimab group, and both groups will receive HAI FOLFOX chemotherapy and IV Bevacizumab.
详细描述
The combination of anti-PD-L1 antibody and bevacizumab has been approved as the first-line treatment for advanced hepatocellular carcinoma (HCC). However, the overall response rate is still unsatisfactory and the prognosis of patients remains poor. Our previous retrospective analysis showed triple combination of hepatic arterial infusion chemotherapy (HAIC) of FOLFOX regimen plus adebrelimab (anti-PD-L1 antibody) and bevacizumab had a high response rate for advanced stage HCC patients. More, as the PD-L1 on intrahepatic tumors is the main target of anti-PD-L1 therapy, hepatic arterial infusion of anti-PD-L1 antibody may contribute to a synergistic effect. Herein, we aimed to evaluate the efficacy and safety of Adabrelimab (arterial or intravenous administration) combined with hepatic artery FOLFOX infusion chemotherapy and Bevacizumab as the first-line treatment of advanced stage hepatocellular carcinoma.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily participate in the study and sign the informed consent form;
- •Aged ≥18 years (calculated as of the date of signing the informed consent form);
- •Diagnosed with hepatocellular carcinoma (HCC) by clinical or pathological means;
- •Barcelona Clinic Liver Cancer (BCLC) stage C, with vascular/bile duct invasion or distant metastasis (excluding cases with Vp4-type tumor thrombus);
- •No prior systemic therapy for HCC; or progression or residual lesions following prior local therapy for HCC (including but not limited to surgery, ablation, radiotherapy, or transarterial chemoembolization [TACE]), with an interval of at least one month between the last local treatment and enrollment;
- •ECOG Performance Status (PS) score of 0-1 and Child-Pugh grade A or grade B with a score of 7;
- •No history of autoimmune disease;
- •An expected survival time of ≥3 months;
- •At least one measurable lesion (per RECIST v1.1 criteria, the longest diameter of the measurable lesion on spiral CT scan must be ≥10 mm or the short axis of enlarged lymph nodes must be ≥15 mm; lesions previously treated locally can be considered target lesions if progression is confirmed per RECIST v1.1 criteria);
- •Sufficient hematologic, hepatic, and renal function, with laboratory tests within the following parameters performed within one week prior to enrollment:
- •Neutrophil count ≥1.5×10^9/L;
- •Platelet count ≥75×10^9/L;
- •Hemoglobin ≥90 g/L;
- •Serum ALT and AST ≤5×upper limit of normal (ULN); ⑤ Serum creatinine ≤1.5×ULN; ⑥ International Normalized Ratio (INR) <2.3, or prothrombin time ≤ULN+6 seconds; ⑦ Albumin ≥30 g/L;
- •Total bilirubin ≤3×ULN.
- •Women of childbearing potential must have a negative serum or urine pregnancy test within seven days prior to study enrollment, must not be breastfeeding, and must agree to use contraceptive measures during the study and for six months after its conclusion; men must agree to use contraceptive measures during the study and for six months after its conclusion.
排除标准
- •Patients with a severe allergy to iodine contrast agents who are unable to undergo hepatic arterial infusion chemotherapy (HAIC);
- •Use of immunosuppressants or systemic corticosteroids for immunosuppressive purposes within one month prior to randomization;
- •Active infections that cannot be effectively controlled;
- •Severe gastroesophageal varices; untreated or incompletely treated gastroesophageal varices (with bleeding or high risk of bleeding);
- •Presence of brain metastases or bone metastases requiring urgent surgical or radiotherapy intervention;
- •Pregnant or suspected to be pregnant, or currently breastfeeding;
- •Current use or recent use (within 10 days before the initiation of the study treatment) of aspirin (>325 mg/day, maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel, and cilostazol;
- •Thrombotic or embolic events, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, or cerebral infarction) or pulmonary embolism, occurring within six months prior to the initiation of the study treatment;
- •Congenital or acquired immunodeficiency;
- •History of other malignant tumors;
- •Any of the following conditions within 12 months prior to the initiation of the study: myocardial infarction, severe/unstable angina, or congestive heart failure;
- •Renal insufficiency requiring dialysis;
- •History of organ transplantation;
- •Severe acute or chronic physical or mental illnesses or laboratory abnormalities that may increase study risks or interfere with result interpretation, rendering the patient unsuitable for enrollment.
研究组 & 干预措施
HAIBrave-001 Arm 1
Arm 1 to receive Hepatic arterial infusion (HAI) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.) + Hepatic artery infusion chemotherapy (HAIC) with FOLFOX regimen
干预措施: intravenous infusion (IV) of Bevacizumab (Bev.) (Drug)
HAIBrave-001 Arm 1
Arm 1 to receive Hepatic arterial infusion (HAI) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.) + Hepatic artery infusion chemotherapy (HAIC) with FOLFOX regimen
干预措施: HAIC with FOLFOX regimen (Procedure)
HAIBrave-001 Arm 2
Intravenous infusion (IV) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.)+ HAIC with FOLFOX regimen
干预措施: HAIC with FOLFOX regimen (Procedure)
HAIBrave-001 Arm 2
Intravenous infusion (IV) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.)+ HAIC with FOLFOX regimen
干预措施: Adebrelimab and bevacizumab maintainance treatment (Drug)
HAIBrave-001 Arm 1
Arm 1 to receive Hepatic arterial infusion (HAI) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.) + Hepatic artery infusion chemotherapy (HAIC) with FOLFOX regimen
干预措施: HAI Adebrelimab (Procedure)
HAIBrave-001 Arm 1
Arm 1 to receive Hepatic arterial infusion (HAI) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.) + Hepatic artery infusion chemotherapy (HAIC) with FOLFOX regimen
干预措施: Adebrelimab and bevacizumab maintainance treatment (Drug)
HAIBrave-001 Arm 2
Intravenous infusion (IV) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.)+ HAIC with FOLFOX regimen
干预措施: intravenous infusion (IV) of Adebrelimab (ADE) (Drug)
HAIBrave-001 Arm 2
Intravenous infusion (IV) of Adebrelimab (ADE) + intravenous infusion (IV) of Bevacizumab (Bev.)+ HAIC with FOLFOX regimen
干预措施: intravenous infusion (IV) of Bevacizumab (Bev.) (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: From first dose until confirmed disease progression, treatment discontinuation, or end of study, whichever occurs first; tumor imaging assessments every 6 weeks (42 ± 7 days), with confirmation of initial response at least 4 weeks later.
Defined as the proportion of enrolled patients in each group who achieve either a complete response (CR) or partial response (PR) as the best response during the study, based on RECIST v1.1 criteria. Radiology imaging evaluations will be conducted every 6 weeks (or after every two treatment cycles) to assess treatment efficacy.
Objective response rate (ORR)
时间窗: 6 weeks
Defined as the proportion of enrolled patients in each group who achieve either a complete response (CR) or partial response (PR) as the best response during the study, based on RECIST v1.1 criteria. Radiology imaging evaluations will be conducted every 6 weeks (or after every two treatment cycles) to assess treatment efficacy.
次要结局
- Progression-free survival (PFS)(36 months)
- Incidence and Severity of Adverse Events (AEs)(From the date of informed consent signature up to 30 days after the last dose of study treatment)
- Overall survival(OS)(36 months)
- Time to progression(36 months)
- Disease control rate(36 months)
- Duration of response(36 months)
- Best overall response(36 months)
研究者
Weijun Fan
Principal Investigator
Sun Yat-sen University