Sequential FOLFOX-HAIC-TACE Plus Sintilimab-Bevacizumab Neoadjuvant Therapy Versus Direct Resection in Resectable High-Risk Recurrence Hepatocellular Carcinoma

Official title

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

Overview

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.

Interventions

• Drug FOLFOX regimen
  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
• Drug Immunotherapy
  sintilimab (200 mg intravenous infusion, q3w)
• Drug targeted therapy
  bevacizumab (15 mg/kg intravenous infusion, q3w)
• Device cTACE
  conventional transarterial chemoembolization

Primary outcome measures

• 2y-RFS [Time frame: From date of randomization until date of first documented recurrence or death from any cause, whichever occurs first, assessed up to 2 years]

Secondary outcome measures (5)

• pCR [Time frame: Perioperative]
• MPR [Time frame: Perioperative]
• ORR [Time frame: Perioperative]
• R0 resection rate [Time frame: Perioperative]
• EFS [Time frame: 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]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07522411 · GDZL032

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗