A Single-arm Exploratory Clinical Study of Tislelizumab Combined With Transarterial Chemoembolization (TACE) and Lenvatinib in the Neoadjuvant Treatment of Resectable CNLC Stage Ⅱa-Ⅱb Hepatocellular Carcinoma
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- recurrence-free survival (RFS)
研究概览
简要总结
In order to improve the R0 resection rate, reduce distant metastasis, and lower postoperative recurrence, there is a growing exploration of surgical treatments for hepatocellular carcinoma (HCC), including preoperative neoadjuvant therapy and postoperative adjuvant therapy. This study is a single-arm, prospective, exploratory clinical trial aimed at evaluating the effectiveness and safety of combining tislelizumab with transarterial chemoembolization (TACE) and lenvatinib as neoadjuvant therapy for resectable CNLC stage IIa-IIb HCC patients. The primary research endpoint of this study is recurrence-free survival (RFS). A total of 20 Chinese HCC patients with stage IIa-IIb and tumors deemed resectable by the investigator are enrolled in this study. For stage IIa patients, the inclusion criteria require meeting any of the following: unclear tumor boundaries, proximity to blood vessels, or suspicious residual margins. The enrolled patients undergo 2 cycles of neoadjuvant therapy, with each cycle consisting of treatment every 3 weeks. On the first day of the first treatment cycle, conventional transarterial chemoembolization (TACE) is performed, and concomitant intravenous infusion of tislelizumab at a dose of 200mg is given, followed by oral administration of lenvatinib at a dose of 8/12mg once daily. On the first day of the second cycle, tislelizumab is again administered intravenously at a dose of 200mg, TACE is not repeated, and lenvatinib treatment is continued. Within 2-4 weeks after the completion of neoadjuvant therapy, the investigator evaluates the tumor's suitability for surgical resection based on comprehensive assessment of imaging results. Subsequently, tumor resection surgery is performed on eligible patients, followed by survival and safety follow-up for the patients.
详细描述
- Background
Primary liver cancer is one of the most common malignancies worldwide, ranking sixth in terms of incidence and third in terms of cancer-related mortality. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, accounting for 85%-90% of cases. Treatment options for HCC include hepatectomy, transplantation, local ablation therapy, transarterial chemoembolization (TACE), radiation therapy, and systemic therapy. Hepatectomy is currently the preferred treatment for HCC, but the five-year recurrence rate after surgery is high, and the overall survival rate for early-stage HCC is relatively low. Therefore, improving the prognosis of HCC is of utmost importance.
In recent years, there has been increasing exploration of surgical treatments for HCC, including neoadjuvant therapy and adjuvant therapy, to increase the R0 resection rate, reduce distant metastasis, and lower the risk of postoperative recurrence. Neoadjuvant therapy for HCC refers to interventions such as preoperative radiotherapy, interventional therapy, targeted therapy, immunotherapy, and portal vein embolization (PVE) administered to patients with resectable HCC who have a high risk of recurrence. These interventions aim to reduce liver inflammation, shrink tumors, and eliminate early-stage microlesions, thereby improving the curative resection rate and overall survival rate.
However, there is limited research supporting neoadjuvant therapy for HCC, and its role in HCC treatment remains unclear. Neoadjuvant therapy has shown preliminary efficacy in various cancers, such as increasing resection rates and preserving sphincter function in colorectal cancer, demonstrating significant effects in early-stage non-small cell lung cancer and advanced malignant melanoma, and showing promise in resectable pancreatic cancer with high-risk factors. Previous explorations of neoadjuvant therapy for HCC have included hepatic artery chemotherapy, radiation therapy, and systemic therapy.
With the emergence of immunotherapy and its promising efficacy in advanced liver cancer, research on immunotherapy as a neoadjuvant treatment has been conducted. Studies have shown that neoadjuvant treatment with immunotherapy in resectable liver cancer has achieved significant tumor necrosis and complete pathological responses. However, current clinical trials have not reached definitive conclusions, and the role of neoadjuvant therapy in patients with resectable HCC remains controversial. Therefore, this study aims to evaluate the efficacy and safety of Tislelizumab in combination with Transarterial Chemoembolization (TACE) and Lenvatinib as neoadjuvant therapy for patients with resectable CNLC stage IIa-IIb hepatocellular carcinoma (HCC), with the goal of providing a better treatment strategy to improve the survival outcomes of these patients. 2. Study Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Participants must voluntarily enroll in this study and provide signed informed consent.
- •Male or female patients between the ages of 18 and 75 years old.
- •Patients diagnosed with hepatocellular carcinoma (HCC) confirmed by histopathology or imaging.
- •Chinese liver cancer staging of IIa-IIb with hepatocellular carcinoma considered resectable by the investigator. For IIa-stage patients, they must meet at least one of the following criteria: unclear tumor margins, proximity to blood vessels, or suspicious residual margins.
- •At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) guidelines (measurable lesions with CT scan long diameter ≥ 10 mm or lymph node lesions with CT scan short diameter ≥ 15 mm, and no prior local treatment such as radiation or cryotherapy).
- •Child-Pugh liver function class A.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •No prior systemic treatment for HCC.
- •For HBsAg-positive patients, HBV-DNA < 200,000 IU/ml (106 copies/ml), and receiving routine antiviral therapy.
- •Expected survival of at least 3 months.
- •Normal major organ function, meeting the following criteria:
- •Hematology criteria:
- •Hemoglobin (HB) ≥ 90 g/L;
- •Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/m3);
- •Platelet count (PLT) ≥ 75 × 109/L.
- •Biochemistry criteria:
- •Total bilirubin (TBIL) ≤ 2 × ULN;
- •ALT, ALP, and AST ≤ 5 × ULN;
- •Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 50 ml/min (calculated using the Cockcroft-Gault formula: CrCL (mL/min) = [(140 - age) × body weight (kg) × F] / (SCr(mg/dL) × 72). Where F=1 for males and F=0.85 for females; SCr=serum creatinine).
- •Coagulation function: International Normalized Ratio (INR) ≤ 2.
- •Blood pressure (BP) controlled with a maximum of 3 antihypertensive medications, defined as BP ≤ 150/90 mmHg at screening, and no changes in antihypertensive treatment within one week before Cycle 1/Day
- •Doppler echocardiography: Left Ventricular Ejection Fraction (LVEF) ≥ lower limit of normal (50%).
- •Women of childbearing potential must use reliable contraceptive methods or undergo pregnancy testing (serum or urine) within 7 days before enrollment, with negative results, and agree to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of investigational drugs. For males, they must agree to use appropriate contraceptive methods during the trial and for 8 weeks after the last dose of investigational drugs or have undergone surgical sterilization.
排除标准
- •Extrahepatic metastasis of primary liver cancer.
- •Diffuse liver cancer with tumor burden ≥ 50% of liver volume; and/or macrovascular invasion of the portal vein classified as Type IV; and/or inferior vena cava tumor thrombosis.
- •Prior treatment with targeted immunotherapy agents, including but not limited to anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) antibodies.
- •Contraindications for Transarterial Chemoembolization (TACE) treatment.
- •Participation in other investigational drug trials within the past 4 weeks.
- •Medical history and comorbidities:1)Active, known, or suspected autoimmune diseases, including a history of allogeneic organ transplantation, allogeneic hematopoietic stem cell transplantation, HIV positive history, or acquired immunodeficiency syndrome (AIDS) history. 2)Severe cardiovascular diseases: Grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia; NYHA Class III-IV heart failure, or left ventricular ejection fraction (LVEF) < 50% based on echocardiography. 3)Active infections. 4)Known allergies to components of Tislelizumab or Lenvatinib. 5)History of substance abuse, alcoholism, or drug addiction.
- •Ineligibility as determined by the investigator.
结局指标
主要结局
recurrence-free survival (RFS)
时间窗: up to 36 months
The period of time from the first day of curative surgery until tumor recurrence or death from any cause.
次要结局
- Overall Survival (OS)(up to 36 months)
- Objective Response Rate (ORR)(10 weeks)
- Major Pathological Response Rate (MPR)(10 weeks)
- R0 Resection Rate(10 weeks)
- Pathological Complete Response Rate (pCR)(10 weeks)
研究者
Zhang Zhibo
Director of Hepatobiliary and Pancreatic Surgery Department
First Affiliated Hospital of Fujian Medical University