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

May 19, 2026 updated by: Binkui Li

Hepatic Arterial Infusion Chemotherapy Plus Sintilimab and Bevacizumab Versus Transarterial Chemoembolization Plus Sintilimab and Bevacizumab for Intermediate-Stage Hepatocellular Carcinoma Beyond the Up-To-Seven Criteria：A Prospective, Randomized, Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
        • Principal Investigator:
          • Binkui Li

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • Albumin ≥ 30 g/L.
  • Coagulation: Normal coagulation function.
  • Expectancy: Expected survival > 3 months.
  • Consent: Signed written informed consent and willingness/ability to comply with follow-up until death, study completion, or termination.

Exclusion Criteria:

  • 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.
  • Non-compliance: History of significant non-compliance with medical protocols or inability to provide reliable informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FOLFOX-HAIC Combination

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.
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).
Active Comparator: TACE Combination

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
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From date of randomization until the date of death from any cause, assessed up to 5 years.
Overall Survival (OS): From randomization to death from any cause.
From date of randomization until the date of death from any cause, assessed up to 5 years.
Objective Response Rate
Time Frame: From date of randomization until the end of systemic treatment (up to 12 months).
Objective Response Rate (ORR): Proportion of patients with CR or PR per mRECIST and RECIST 1.1.
From date of randomization until the end of systemic treatment (up to 12 months).
Disease Control Rate
Time Frame: From date of randomization until the end of systemic treatment (up to 12 months).
Disease Control Rate (DCR): Proportion of patients with CR, PR, or SD.
From date of randomization until the end of systemic treatment (up to 12 months).
Duration of Response
Time Frame: From initial response (CR or PR) to the date of first documented progression or death，assessed up to 5 years.
From initial response (CR or PR) to the date of first documented progression or death
From initial response (CR or PR) to the date of first documented progression or death，assessed up to 5 years.
Time to Progression
Time Frame: From date of randomization to the date of first objective tumor progression, assessed up to 5 years.
From date of randomization to the date of first objective tumor progression
From date of randomization to the date of first objective tumor progression, assessed up to 5 years.
Conversion Rate
Time Frame: From date of randomization until the end of the conversion therapy assessment (typically within 12 months).
Conversion Rate: Percentage of patients achieving surgical resection eligibility.
From date of randomization until the end of the conversion therapy assessment (typically within 12 months).
Safety Profile
Time Frame: From randomization until 1 year after the last dose of study treatment.
Safety Profile: Incidence of adverse events per NCI CTCAE v5.0.
From randomization until 1 year after the last dose of study treatment.
Patient-Reported Outcomes
Time Frame: Baseline and every 1 month until the end of month 12.
Patient-Reported Outcomes (PRO): Quality of life using IL42-EORTC QLQ-C30.
Baseline and every 1 month until the end of month 12.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Binkui Li

Investigators

  • Principal Investigator: Binkui Li, Sun Yat-sen University Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 15, 2026

Primary Completion (Estimated)

May 30, 2030

Study Completion (Estimated)

May 30, 2030

Study Registration Dates

First Submitted

May 12, 2026

First Submitted That Met QC Criteria

May 12, 2026

First Posted (Actual)

May 18, 2026

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 19, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2026-143-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatocellular Carcinoma

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kenya

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe