HAIC vs. TACE Combined With Sintilimab and Bevacizumab for Intermediate HCC (Beyond Up-To-Seven)

NCT07594340 | Recruiting Phase 3

• 1 other identifier: B2026-143-01
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this prospective, randomized, multicenter, controlled clinical study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) compared to transarterial chemoembolization (TACE) when both are combined with sintilimab and bevacizumab for patients with intermediate-stage hepatocellular carcinoma (HCC). Specifically, the trial focuses on patients with a high tumor burden that exceeds the Up-To-Seven criteria.While TACE is the standard treatment for BCLC stage B HCC, its effectiveness is often limited in patients with extensive intrahepatic tumor loads. This study investigates whether the combination of FOLFOX-HAIC and systemic therapy (sintilimab plus bevacizumab) provides better local control and survival outcomes than the combination of TACE and the same systemic therapy. Experimental Group: Patients receive FOLFOX-HAIC (up to 4 cycles in the first 16 weeks) combined with sintilimab and bevacizumab. Control Group: Patients receive on-demand TACE (up to 4 cycles in the first 16 weeks) combined with sintilimab and bevacizumab. Primary Objective: To compare Progression-Free Survival (PFS) between the two arms as evaluated by mRECIST. Enrollment: A total of 300 patients will be randomized at a 1:1 ratio to the treatment groups. The study aims to provide high-level clinical evidence for optimizing treatment strategies for this specific subgroup of HCC patients.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Progression-Free Survival (PFS): From randomization to first documentation of progression (mRECIST) or death from any cause.

  From date of randomization until the date of first documented progression (per mRECIST) or date of death from any cause, assessed up to 5 years.

Secondary Outcomes (8)

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 5 years.

• Objective Response Rate

  From date of randomization until the end of systemic treatment (up to 12 months).

• Disease Control Rate

  From date of randomization until the end of systemic treatment (up to 12 months).

• Duration of Response

  From initial response (CR or PR) to the date of first documented progression or death，assessed up to 5 years.

• Time to Progression

  From date of randomization to the date of first objective tumor progression, assessed up to 5 years.

Study Arms (2)

FOLFOX-HAIC Combination

EXPERIMENTAL

Intervention: Drug (Sintilimab): 200mg IV Q3W (Up to 12 months). Drug (Bevacizumab): 15mg/kg IV Q3W (Up to 12 months). Procedure (FOLFOX-HAIC): Max 4 cycles within first 16 weeks. Oxaliplatin: 130mg/m² infusion (2h). Leucovorin: 400mg/m² infusion (2h). 5-FU: 400mg/m² bolus (10min) + 1200mg/m² infusion (23h).

Procedure: Procedure (FOLFOX-HAIC): Max 4 cycles within first 16 weeks.

TACE Combination

ACTIVE COMPARATOR

Intervention: Drug (Sintilimab): 200mg IV Q3W (Up to 12 months). Drug (Bevacizumab): 15mg/kg IV Q3W (Up to 12 months). Procedure (TACE): On-demand (max 4 cycles within 16 weeks). Epirubicin (30mg/m²) + Lobaplatin (30-50mg) + Lipiodol (5-20ml).

Procedure: TACE (transarterial chemoembolization) combined with targeted/immunotherapy

Interventions

Procedure (FOLFOX-HAIC): Max 4 cycles within first 16 weeks. PROCEDURE

Drug (Sintilimab): 200mg IV Q3W (Up to 12 months). Drug (Bevacizumab): 15mg/kg IV Q3W (Up to 12 months). Procedure (FOLFOX-HAIC): Max 4 cycles within first 16 weeks. Oxaliplatin: 130mg/m² infusion (2h). Leucovorin: 400mg/m² infusion (2h). 5-FU: 400mg/m² bolus (10min) + 1200mg/m² infusion (23h).

FOLFOX-HAIC Combination

TACE (transarterial chemoembolization) combined with targeted/immunotherapy PROCEDURE

Drug (Sintilimab): 200mg IV Q3W (Up to 12 months). Drug (Bevacizumab): 15mg/kg IV Q3W (Up to 12 months). Procedure (TACE): On-demand (max 4 cycles within 16 weeks). Epirubicin (30mg/m²) + Lobaplatin (30-50mg) + Lipiodol (5-20ml).

TACE Combination

Eligibility Criteria

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

You may qualify if:

• Diagnosis: Histologically or cytologically confirmed hepatocellular carcinoma (HCC), or patients with cirrhosis meeting the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria for HCC.
• Age: ≥ 18 years old.
• Performance Status: ECOG performance status score of 0.
• Prior Treatment: No prior systemic anti-tumor therapy or transarterial interventional therapy for HCC.
• Tumor Stage and Burden: Barcelona Clinic Liver Cancer (BCLC) Stage B, unsuitable for radical surgery and/or local therapy (such as ablation).
• Up-To-Seven Criteria: Tumor burden exceeding the Up-To-Seven criteria, defined as the sum of the size of the largest intrahepatic tumor (in cm) and the number of tumors being greater than 7.
• Tumor Distribution: Bilobar multifocal tumors.
• Measurable Disease: At least one measurable lesion with arterial phase enhancement on CT/MRI.
• Vascular Status: Patent portal vein with no evidence of portal vein tumor thrombus.
• Extrahepatic Status: No extrahepatic metastasis.
• Variceal Risk: No risk of variceal bleeding; esophagogastroduodenoscopy (EGD) within 6 months shows no gastroesophageal varices or active ulcers.
• Liver Function: Child-Pugh Grade A.
• Hematology: Platelets \> 75 × 10⁹/L; White Blood Cells \> 3.0 × 10⁹/L; Neutrophils \> 1.5 × 10⁹/L.
• Biochemistry: Serum bilirubin ≤ 1.5 × upper limit of normal (ULN); Transaminases ≤ 3 × ULN; Serum creatinine \< 1.5 × ULN.
• Physical Findings: No ascites

You may not qualify if:

• Histology: Known histology/cytology of fibrolamellar HCC, sarcomatoid HCC, or components of cholangiocarcinoma.
• Medical History: History of hepatic encephalopathy or liver transplantation.
• Effusions: Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage.
• Viral Hepatitis: Active Hepatitis B (HBV DNA \> 2000 IU/ml or 10⁴ copies/ml) or Hepatitis C (HCV RNA \> 10³ copies/ml); co-infection with both HBsAg and anti-HCV positive. (Eligible if levels drop below these criteria after nucleoside antiviral therapy) .
• Cardiovascular (Past 12 Months): Myocardial infarction, severe/unstable angina, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack), or pulmonary embolism.
• Ongoing Cardiac Issues: Arrhythmia ≥ Grade 2 (NCI-CTCAE); QTc prolongation (Male \> 450 ms, Female \> 470 ms).
• Bleeding Risk: History of gastrointestinal bleeding within 6 months or clear bleeding tendency (e.g., high-risk varices, active GI ulcer, persistent positive fecal occult blood).
• Hypertension: Uncontrollable hypertension (SBP \> 140 mmHg or DBP \> 90 mmHg despite optimal treatment); history of hypertensive crisis or hypertensive encephalopathy.
• Organ Failure: Renal failure requiring hemodialysis or peritoneal dialysis; severe dysfunction of other major organs.
• Second Malignancy: History of other malignancies within 3 years prior to screening (except those with negligible risk of metastasis/death such as treated cervical cancer in situ, non-melanoma skin cancer, or localized prostate cancer).
• CNS Involvement: Known or new evidence of brain or leptomeningeal lesions. Coagulation Disorders: Hemophilia or bleeding tendency; currently taking therapeutic doses of coumarin derivatives (e.g., warfarin).
• Pregnancy/Lactation: Pregnant or breastfeeding females; women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
• Other History: Prior organ transplant; known HIV infection; active tuberculosis; allergy to chemotherapy drugs.
• Autoimmune Diseases: Active or history of autoimmune diseases (e.g., myasthenia gravis, myositis, autoimmune hepatitis, SLE, rheumatoid arthritis, IBD, etc.).
• General Compliance: Any serious acute/chronic physical or mental illness, or laboratory abnormalities that increase study risk or interfere with interpretation of results.

Sponsors & Collaborators

• Binkui Li: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Immunotherapy

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

Study Officials

• Binkui Li

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei He

CONTACT

+8618666014207; hewei@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 12, 2026
• First Posted: May 18, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): May 30, 2030
• Study Completion (Estimated): May 30, 2030
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

CN (1)