TACE or Ablation Combined With Sintilimab and Ipilimumab N01 as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma With Intermediate-High Recurrence Risk: A Multicenter, Multigroup, Randomized, Phase Ⅱ Exploratory Clinical Trial
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Sun Yat-sen University
- 入组人数
- 90
- 主要终点
- 1-year recurrence-free survival rate
概览
简要总结
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:
- TACE or ablation combined with anti-CTLA-4 and anti-PD-1 immunotherapy;
- TACE or ablation combined with anti-CTLA-4 + anti-PD-1 + lenvatinib;
- Dual immunotherapy with anti-CTLA-4 and anti-PD-1;
- Anti-CTLA-4 + anti-PD-1 + lenvatinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1\) Age: 18-75 years old; 2) Patients with hepatocellular carcinoma (HCC) classified as CNLC stage Ib-IIIa (excluding patients with Vp3 and Vp4), and deemed resectable by multidisciplinary team (MDT) discussion;
- •3\) No prior tumor-related treatment received;
- •4\) At least one measurable target lesion according to the RECIST 1.1 criteria;
- •5\) ECOG PS score of 0-1;
- •6\) Liver function classification: Child-Pugh Class A;
- •7\) Estimated survival time ≥ 12 weeks;
- •8\) Hematological, liver, and renal functions meet the following criteria:
- •Hemoglobin concentration ≥ 90 g/L;
- •Neutrophil count ≥ 1.5 × 10⁹/L;
- •Platelet count ≥ 75 × 10⁹/L;
排除标准
- •1\) Prior history of HCC treatment; 2) Tumor rupture and bleeding, or suspected peritoneal metastasis;
- •3\) History of other complex surgeries within 6 weeks;
- •4\) Prior history of organ transplantation;
- •Currently receiving treatment in other clinical trials;
- •5\) Prior history of autoimmune diseases, inflammatory disorders (such as inflammatory bowel disease, etc.), diverticulitis, systemic lupus erythematosus, sarcoidosis syndrome, Wegener's syndrome (granulomatosis with polyangiitis, rheumatoid arthritis, etc.), except for the following cases: vitiligo or alopecia areata, hypothyroidism with stable condition after drug replacement therapy, chronic skin diseases that do not require systemic treatment, and celiac disease controllable by diet alone;
- •6\) Prior history of allergy to anti-PD1 drugs or anti-CTLA4 drugs, or allergy to chemical molecules similar to the above drugs, or prior severe allergic reaction to other monoclonal antibodies;
- •7\) Uncontrollable intermittent recurrent diseases, including but not limited to: persistent infections (including tuberculosis), hypertension uncontrollable by drugs (\> 140/90 mmHg), interstitial lung disease, severe chronic gastrointestinal diseases complicated with diarrhea, mental illness or social disorders that cannot comply with clinical research requirements, factors with high risk of side effects, and inability to sign the informed consent form;
- •8\) Patients with prior hepatic encephalopathy, refractory ascites, or esophagogastric varices with high bleeding risk; patients with upper gastrointestinal bleeding within 1 year before the first administration;
- •9\) Untreated active hepatitis B subjects (HBsAg positive and HBV-DNA exceeding 5000 copies/mL (1000 IU/mL) or higher than the lower limit of detection, whichever is higher); for subjects with hepatitis B, anti-hepatitis B virus treatment is required during the study treatment; active hepatitis C subjects (HCV antibody positive and HCV-RNA level higher than the lower limit of detection);
- •10\) Patients with primary brain tumors (except meningiomas or other benign brain tumors), or any brain metastases, leptomeningeal carcinomatosis, epilepsy uncontrollable by conventional drugs, or new-onset stroke within 1 year;
结局指标
主要结局
1-year recurrence-free survival rate
时间窗: One year
The proportion of subjects who did not experience tumor recurrence or death within 1 year after surgery.
次要结局
- major pathological response rate, MPR rate(5 weeks)
- Objective response rate, ORR(5 weeks)
- Adverse Events, AE(One year)
研究者
Ming Kuang
Professor
Sun Yat-sen University