Neoadjuvant HAIC and PD-1 Plus Adjuvant PD-1 for High-risk Recurrent HCC
NCT Number: NCT06467799
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Hepatocellular Carcinoma|Beyond Milan Criteria
Interventions: DRUG: Neoadjuvant HAIC and PD-1 Plus Adjuvant PD-1
Sponsor: Sun Yat-sen University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 39
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-07-01
Completion Date: 2026-07-01

Summary:
Surgical resection is the primary curative treatment for patients with hepatocellular carcinoma (HCC), with a 5-year overall survival rate of 60-80% post-surgery. Therefore, guidelines recommend surgical resection as the first-line choice for early to mid-stage HCC (CNLC stages IA-IIA or BCLC stages A/B) patients with well liver reserve function. However, the high postoperative recurrence rate is the main factor limiting long-term survival in HCC patients, with literature reporting recurrence rates exceeding 70%. Among these, half of the patients experience recurrence within two years post-surgery, imposing a heavy burden on patients' physical and mental health as well as on societal medical resources. Adopting effective treatment to improve surgical curability and reduce postoperative recurrence rates is one of the current research hotspots.

Recent studies from the investigators' center indicate that hepatic arterial infusion chemotherapy (HAIC) and immunotherapy can provide definite efficacy for patients with advanced HCC, extending their survival time. Mechanistically, chemotherapy and immunotherapy have synergistic effects: tumor cell necrosis induced by chemotherapy can promote immune activation, while cytokines and neutralizing antibodies secreted by immune cells can enhance the toxicity of chemotherapeutic drugs.

Therefore, this study aims to conduct a prospective, single-arm, phase II clinical study, targeting HCC patients with high-risk recurrence factors, to evaluate whether neoadjuvant HAIC combined with a PD-1 monoclonal antibody (Tislelizumab) followed by adjuvant Tislelizumab post-surgery can reduce postoperative recurrence rates in HCC patients. The primary endpoint is the 1-year recurrence-free survival (RFS) rate post-surgery, while secondary endpoints include the objective response rate (ORR) of neoadjuvant therapy, the incidence of perioperative complications, the incidence of treatment-related adverse events, overall survival (OS) time, pathological complete response (pCR) rate of neoadjuvant therapy, and major pathological response (MPR) of neoadjuvant therapy. The investigators aim to comprehensively assess the efficacy and safety of neoadjuvant HAIC plus PD-1 and adjuvant PD-1 in the perioperative treatment of HCC.

Primary Outcome Measures: recurrence free survival, RFS, RFS is defined as the time from treatment to post-resection tumor recurrence or death from any cause., From date of treatment beginning until the date of first documented tumor recurrence or date of death from any cause, whichever came first, assessed up to 1 years
Secondary Outcome Measures: objective response rate，ORR, The ratio of patients achieving the best efficacy of neoadjuvant therapy, including complete response (CR) and partial response (PR), to all patients., From date of neoadjuvant treatment beginning until the date of neoadjuvant treatment completion, up to 1 year.|pathological complete response，pCR, The ratio of patients with no viable tumor cells in the pathology after resection to all patients undergoing surgical resection., From date of neoadjuvant treatment beginning until the date of surgical resection completion, , up to 1 year.|overall survival, OS, OS is defined as the time from randomization to death from any cause., From date of treatment beginning until the date of death from any cause, assessed up to 1 years.|perioperative complication rate, Perioperative complication includes intraoperative complications such as bleeding and transfusion, extensive adhesions, diaphragm resection, prolonged surgery time, etc., as well as postoperative complications such as bleeding, infection, bile leakage, liver dysfunction, etc., The period from the start of surgery to the patient's discharge from hospital, up to 1 year.|Incidence of adverse events (safety ), Treatment-related adverse events are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0)., From date of neoadjuvant treatment beginning until the date of adjuvant treatment completion, up to 2 year.