Efficacy and Safety of Sequential FOLFOX-HAIC Followed by TACE Combined With Sintilimab Plus Bevacizumab as Neoadjuvant Therapy, Followed by Surgical Resection, Versus Direct Surgical Resection in Patients With Resectable Hepatocellular Carcinoma and High-Risk Recurrence Factors: A Single-Center, Open-Label, Two-Arm, Randomized Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 主要终点
- 2y-RFS
研究概览
简要总结
This study is designed to evaluate the efficacy and safety of sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE as the perioperative adjuvant therapy in surgical resection to hepatocellular carcinoma with high-risk features. (1) Evaluate for some high-risk patients with resectable tumours, whether or not sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE reduces the risk of recurrence and improves the survival of patients. (2) Evaluate the safety of sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE for the neoadjuvant therapy of resectable 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.Fully understanding and voluntarily signing the informed consent form, complying with the requirements and evaluation schedule of this study; 2.18 to 75 years old; 3.Hepatocellular carcinoma diagnosed by histopathology; 4.Imaging examination results meeting the definition of high-risk recurrence risk factors in this study: 2-4 multiple tumors; the size of the dominant tumor was >=5 cm; CNLC-Ⅲa incorporated with portal vein tumor thrombus [Vp1/2/3]; 5.Surgical evalution with a radically resectable tumor; 6.Child-Pugh class A; 7.ECOG PS： 0~1; 8.hepatocellular carcinoma who had never received previous form of systemic therapy; 9.At least one measurable lesion that can be accurately assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for assessment per mRECIST 1.1; 10.The main organ functions are normal, including the following criteria: (1) sufficient bone marrow function, defined as neutrophils ≥ 1.5 × 10 ^ 9/L, hemoglobin (Hb) ≥ 90 g/dL, platelets ≥ 50 × 10 ^ 9/L; (2) good liver function, defined as serum total bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN, albumin ≥ 28 g/L; (3) good coagulation function, defined as international normalized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding the normal control range ≤ 3 seconds; (4) Adequate renal function， defined as glomerular filtration rate (GFR)>90mL/min; 11.Female participants of childbearing potential have negative results on a pregancy test in 3 days before the first utilization of medicine and male or female participants with partners of child-bearing potential had to use a medically acceptable method of contraception through 180 days after taking study drug
排除标准
- •Pregnant or lactating women;
- •Patients with a history of other malignancies within the past 5 years, excluding basal cell carcinoma of the skin， cervical carcinoma in situ and/or thyroid papillary carcinoma have been cured;
- •Patients who are known to be allergic to the trial drugs, finolizumab and bevacizumab；
- •Previous history of upper gastrointestinal bleeding or current presence of a clear bleeding risk disease;
- •Patients with uncontrolled cardiac clinical symptoms or diseases；
- •Uncontrolled cardiac symptoms or diseases, including but not limited to (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, and (4) clinically important significant supraventricular or ventricular arrhythmias requiring clinical intervention；
- •Patients with any active autoimmune disease or history of autoimmune disease；
- •Have a history of immune deficiency, including HIV-positive test results, or suffer from other acquired or congenital immune deficiency diseases, or have a history of organ transplantation and bone marrow transplantation;
- •History of mental illness, and abuse of psychiatric drugs and narcotics;
- •Severe uncontrolled recurrent infections or other serious uncontrolled concomitant diseases;
- •Situations that researchers assessed as unsuitable for inclusion in this study.
研究组 & 干预措施
Group A（ Intervention group)
2-4 cycles of quadruple therapy (3 weeks per cycle) consisting of neoadjuvant FOLFOX-HAIC (oxaliplatin 85 mg/m² intra-arterial infusion over 2 hours; leucovorin calcium 200 mg/m² intra-arterial infusion over 2 hours; 5-fluorouracil 400 mg/m² intra-arterial bolus followed by 2400 mg/m² continuous intra-arterial infusion over 46 hours) sequentially combined with cTACE, sintilimab (200 mg intravenous infusion, q3w) and bevacizumab (15 mg/kg intravenous infusion, q3w). Tumor response was evaluated every 2 cycles, and radical resection was performed based on assessment results. After radical hepatectomy, patients continued to receive sintilimab plus bevacizumab for 8 cycles within 4-12 weeks postoperatively.
干预措施: FOLFOX regimen (Drug)
Group A（ Intervention group)
2-4 cycles of quadruple therapy (3 weeks per cycle) consisting of neoadjuvant FOLFOX-HAIC (oxaliplatin 85 mg/m² intra-arterial infusion over 2 hours; leucovorin calcium 200 mg/m² intra-arterial infusion over 2 hours; 5-fluorouracil 400 mg/m² intra-arterial bolus followed by 2400 mg/m² continuous intra-arterial infusion over 46 hours) sequentially combined with cTACE, sintilimab (200 mg intravenous infusion, q3w) and bevacizumab (15 mg/kg intravenous infusion, q3w). Tumor response was evaluated every 2 cycles, and radical resection was performed based on assessment results. After radical hepatectomy, patients continued to receive sintilimab plus bevacizumab for 8 cycles within 4-12 weeks postoperatively.
干预措施: Immunotherapy (Drug)
Group A（ Intervention group)
2-4 cycles of quadruple therapy (3 weeks per cycle) consisting of neoadjuvant FOLFOX-HAIC (oxaliplatin 85 mg/m² intra-arterial infusion over 2 hours; leucovorin calcium 200 mg/m² intra-arterial infusion over 2 hours; 5-fluorouracil 400 mg/m² intra-arterial bolus followed by 2400 mg/m² continuous intra-arterial infusion over 46 hours) sequentially combined with cTACE, sintilimab (200 mg intravenous infusion, q3w) and bevacizumab (15 mg/kg intravenous infusion, q3w). Tumor response was evaluated every 2 cycles, and radical resection was performed based on assessment results. After radical hepatectomy, patients continued to receive sintilimab plus bevacizumab for 8 cycles within 4-12 weeks postoperatively.
干预措施: targeted therapy (Drug)
Group A（ Intervention group)
2-4 cycles of quadruple therapy (3 weeks per cycle) consisting of neoadjuvant FOLFOX-HAIC (oxaliplatin 85 mg/m² intra-arterial infusion over 2 hours; leucovorin calcium 200 mg/m² intra-arterial infusion over 2 hours; 5-fluorouracil 400 mg/m² intra-arterial bolus followed by 2400 mg/m² continuous intra-arterial infusion over 46 hours) sequentially combined with cTACE, sintilimab (200 mg intravenous infusion, q3w) and bevacizumab (15 mg/kg intravenous infusion, q3w). Tumor response was evaluated every 2 cycles, and radical resection was performed based on assessment results. After radical hepatectomy, patients continued to receive sintilimab plus bevacizumab for 8 cycles within 4-12 weeks postoperatively.
干预措施: cTACE (Device)
Group B ( Control group)
hepatectomy, and sintilimab was administered for 8 cycles with in 4 to 12 weeks after hepatectomy
干预措施: Immunotherapy (Drug)
结局指标
主要结局
2y-RFS
时间窗: From date of randomization until date of first documented recurrence or death from any cause, whichever occurs first, assessed up to 2 years
2-year recurrence-free survival rate
次要结局
- pCR(Perioperative)
- MPR(Perioperative)
- ORR(Perioperative)
- R0 resection rate(Perioperative)
- EFS(the time from randomization to the first occurrence of any of the following events: disease progression precluding surgery, local or distant recurrence, or death from any cause，assessed up to 2 years)
研究者
BinYong Liang
Department of Hepatobiliary and Pancreatic Sugery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Tongji Hospital