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

NCT07522411 | Not Yet Recruiting Phase 1

• 1 other identifier: GDZL032
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Group A（ Intervention group)

EXPERIMENTAL

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; Drug: Immunotherapy; Drug: targeted therapy; Device: cTACE

Group B ( Control group)

OTHER

hepatectomy, and sintilimab was administered for 8 cycles with in 4 to 12 weeks after hepatectomy

Drug: Immunotherapy

Interventions

FOLFOX regimen DRUG

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

Also known as: HAIC

Group A（ Intervention group)

Immunotherapy DRUG

sintilimab (200 mg intravenous infusion, q3w)

Also known as: sintilimab

Group A（ Intervention group); Group B ( Control group)

targeted therapy DRUG

bevacizumab (15 mg/kg intravenous infusion, q3w)

Also known as: bevacizumab

Group A（ Intervention group)

cTACE DEVICE

conventional transarterial chemoembolization

Group A（ Intervention group)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Beijing Bethune Charitable Foundation: collaborator
• BinYong Liang: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Folfox protocol; Immunotherapy; sintilimab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

BinYong Liang, M.D.

CONTACT

8615927271139; Binyong.liang@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Department of Hepatobiliary and Pancreatic Sugery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 13, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04