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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: FOLFOX regimen; Drug: Immunotherapy; Drug: targeted therapy; Device: cTACE

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BinYong Liang, M.D.; Phone Number: 8615927271139; Email: Binyong.liang@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

1. Pregnant or lactating women;
2. 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;
3. Patients who are known to be allergic to the trial drugs, finolizumab and bevacizumab；
4. Previous history of upper gastrointestinal bleeding or current presence of a clear bleeding risk disease;
5. Patients with uncontrolled cardiac clinical symptoms or diseases；
6. 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；
7. Patients with any active autoimmune disease or history of autoimmune disease；
8. 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;
9. History of mental illness, and abuse of psychiatric drugs and narcotics;
10. Severe uncontrolled recurrent infections or other serious uncontrolled concomitant diseases;
11. Situations that researchers assessed as unsuitable for inclusion in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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; Other Names: HAIC; Drug: Immunotherapy; sintilimab (200 mg intravenous infusion, q3w); Other Names: sintilimab; Drug: targeted therapy; bevacizumab (15 mg/kg intravenous infusion, q3w); Other Names: bevacizumab; Device: cTACE; conventional transarterial chemoembolization
Other: Group B ( Control group); hepatectomy, and sintilimab was administered for 8 cycles with in 4 to 12 weeks after hepatectomy	Drug: Immunotherapy; sintilimab (200 mg intravenous infusion, q3w); Other Names: sintilimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2y-RFS	2-year recurrence-free survival rate	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

Outcome Measure	Measure Description	Time Frame
pCR	pathological Complete Response，defined as the absence of residual invasive tumor cells in the primary tumor and regional lymph nodes in the resected specimen after neoadjuvant therapy.	Perioperative
MPR	Major Pathological Response，presence of viable tumor cells ≤30% in the primary tumor and lymph nodes after radical resection	Perioperative
ORR	Objective Response Rate，the proportion of patients who achieved complete response (CR) or partial response (PR) in tumor shrinkage according to the mRECIST v1.1 criteria and maintained the response for at least 8 weeks	Perioperative
R0 resection rate	The proportion of patients who achieved radical R0 resection among those who underwent surgery.	Perioperative
EFS	Event-Free Survival, defined as 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.	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

Collaborators and Investigators

• Sponsor: BinYong Liang
• Collaborators: Beijing Bethune Charitable Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Therapy; Immunomodulation; Bevacizumab; Immunotherapy; Folfox protocol; sintilimab
• Other Study ID Numbers: GDZL032

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No