Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The recurrence rate after curative resection for early-stage HCC remains extremely high, with 2-year and 5-year recurrence rates reaching 50% and 70%, respectively. Currently, no standard perioperative treatment is recommended in domestic and international guidelines. Recently, data from a phase III clinical study, investigating neoadjuvant and adjuvant therapy with camrelizumab plus apatinib in resectable HCC patients at intermediate-to-high risk of recurrence, demonstrated that the neoadjuvant and adjuvant therapy combining targeted therapy and immunotherapy could significantly reduce postoperative recurrence. The median recurrence-free survival (RFS) in the target-immunotherapy group was 42.1 months, which was remarkably longer than 19.4 months in the surgery-alone group. Local therapies (TACE, ablation) can induce immunogenic cell death of tumors and remodel the tumor microenvironment, thereby exerting synergistic effects with immunotherapy. This strategy is expected to further improve recurrence-free survival in HCC patients after surgery. This clinical trial aims to explore the efficacy and tolerability of the following regimens compared with surgery alone: 1. TACE or ablation combined with anti-CTLA-4 and anti-PD-1 immunotherapy; 2. TACE or ablation combined with anti-CTLA-4 + anti-PD-1 + lenvatinib; 3. Dual immunotherapy with anti-CTLA-4 and anti-PD-1; 4. Anti-CTLA-4 + anti-PD-1 + lenvatinib. Efficacy differences between groups will be compared using Bayesian statistical methods based on non-informative priors.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
105
200mg ivdrip q3w
3mk/kg ivdrip q3w
8mg P.O QD
TACE will be performed in accordance with the standard procedures of the respective medical centers.Based on the judgment of the MDT team, patients with at least one lesion amenable to complete ablation will receive ablation therapy.Patients without any lesion amenable to complete ablation will receive TACE therapy.
Ablation will be performed in accordance with the standard procedures of the respective medical centers.Based on the judgment of the MDT team, patients with at least one lesion amenable to complete ablation will receive ablation therapy.Patients without any lesion amenable to complete ablation will receive TACE therapy.
1-year recurrence-free survival rate
The proportion of subjects who did not experience tumor recurrence or death within 1 year after surgery.
Time frame: One year
major pathological response rate, MPR rate
The proportion of patients with histologically confirmed tumor necrosis of more than 90% in the surgically resected specimens.
Time frame: 5 weeks
Objective response rate, ORR
The proportion of patients who achieve complete response (CR) and partial response (PR) in tumor assessment according to the RECIST 1.1 criteria after neoadjuvant therapy and before surgical resection.
Time frame: 5 weeks
Adverse Events, AE
The proportion of patients who experienced grade ≥3 hematological or non-hematological adverse events from the start of treatment to the end of follow-up.
Time frame: One year
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