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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
300
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).
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).
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGProgression-Free Survival
Progression-Free Survival (PFS): From randomization to first documentation of progression (mRECIST) or death from any cause.
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.
Overall Survival
Overall Survival (OS): From randomization to death from any cause.
Time frame: From date of randomization until the date of death from any cause, assessed up to 5 years.
Objective Response Rate
Objective Response Rate (ORR): Proportion of patients with CR or PR per mRECIST and RECIST 1.1.
Time frame: From date of randomization until the end of systemic treatment (up to 12 months).
Disease Control Rate
Disease Control Rate (DCR): Proportion of patients with CR, PR, or SD.
Time frame: 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
Time frame: 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
Time frame: From date of randomization to the date of first objective tumor progression, assessed up to 5 years.
Conversion Rate
Conversion Rate: Percentage of patients achieving surgical resection eligibility.
Time frame: From date of randomization until the end of the conversion therapy assessment (typically within 12 months).
Safety Profile
Safety Profile: Incidence of adverse events per NCI CTCAE v5.0.
Time frame: From randomization until 1 year after the last dose of study treatment.
Patient-Reported Outcomes
Patient-Reported Outcomes (PRO): Quality of life using IL42-EORTC QLQ-C30.
Time frame: Baseline and every 1 month until the end of month 12.
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