Efficacy and Safety of Lenvatinib as a Conversion Therapy in Patients With Potentially Resectable Hepatocellular Carcinoma: A Single-Arm and Open-Label Prospective Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Resection rate
研究概览
简要总结
Lenvatinib is the standard of care for patients with advanced hepatocellular carcinoma (HCC). The aim of the single-arm, open-label, phase II clinical trial is to assess efficacy and safety of lenvatinib as a preoperative conversion therapy in patients with potentially resectable HCC. Investigator hypothesized that lenvatinib may be an effective conversion treatment for HCC, and preoperative treatment with lenvatinib can improve resectability in patients with potential resectable HCC and improve the long term survival.
详细描述
For patients with potentially resectable HCC (intermediate or advanced stage), upfront therapy with surgical resection is of high recurrence rate after surgery. The aim of the single-arm, open-label, prospective phase II clinical trial is to evaluate whether preoperative lenvatinib treatment could improve resectability and therefore improve the long term survival.
Participants who are recruited in this study in this study will be treated with lenvatinib and will be evaluated for the feasibility for surgical resection by a multidisciplinary team every 8 weeks. If the participants underwent curative resection, they will receive lenvatinib treatment for 48 weeks after surgery.
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
- •Male or female aged 18-75;
- •The participant must have confirmed diagnosis of HCC histologically or clinically;
- •The participant must have at least one untreated intrahepatic lesion that can be evaluated by contrast-enhanced CT or MRI;
- •The BCLC stage B/C patients, more than 3 tumor nodes or have portal vein tumor thrombus (Vp3-Vp4 according to LCSGJ PVTT classification) or extrahepatic metastases limited to one organ and the number of metastases nodules is no more than 3;
- •ECOG PS 0-1 and Child-Pugh A;
- •Surgical resection is not the first choice according to MDT evaluation;
- •Written informed consent;
排除标准
- •WBC<4.0*10^9/L, HB<80 g/L, PLT<75*10^9/L and NEUT<1.5×10^9/L;
- •Coagulation function: (prothrombin time) international normalized ratio (INR) >1.2;
- •Liver function: serum albumin (ALB)<3.5 g/dl, total bilirubin (TBIL)>1.5 times the upper limit of normal range, alanine aminotransferase and aspartate aminotransferase (ALT and AST)>3 times the upper limit of normal range; renal function index: serum creatinine (CRE)>1.5 times the upper limit of normal range; uncontrolled hypertension (>150/90mm Hg);
- •Lymph node metastasis to hilar of lung or liver, or peripheral tissue adhesion;
- •Participated in other clinical trials 30 days before enrollment;
- •With ascites, hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis;
- •Suspected allergy to study drug;
- •With other organ dysfunction, it is not expected to be tolerated general anesthesia or hepatectomy;
- •Other conditions that the investigators considered not unsuitable for inclusion.
研究组 & 干预措施
Treatment
The patients will receive lenvatinib treatment and will be evaluated for the feasibility of liver resection every 8 weeks. For those who underwent liver resection, they will receive lenvatinib treatment for another 48 weeks. In case of tumor recurrence, intolerance, death, or need for other antitumor treatment, the treatment shall be stopped.
干预措施: Lenvatinib 4 mg Oral (Drug)
结局指标
主要结局
Resection rate
时间窗: 1 year after LPI
The percentage of patients who receive curative liver resection for HCC. The criteria for curative resection: (1) no active tumor thrombosis is observed in hepatic veins, portal veins, bile ducts or inferior vena cava; or the type of portal vein invasion was converted from Vp3/Vp4 to Vp1/Vp2; (2) no active metastasis to adjacent organs or distant organs, or to lymph nodes; (3) the surgical margin ≥ 0.5 cm; (4) the number of active tumor nodules decreases from ≥4 to \<4; (5) the ratio of future liver volume to standard liver volume increases from \<40% to ≥40% (for those with liver cirrhosis) or from \<30% to ≥30% (for those without liver cirrhosis).
次要结局
- Overall survival (OS)(3 years)
- Serum Biomarkers(1 year after LPI)
- Adverse events(AE) and Serious adverse events(SAE)(1 year after LPI)
- Objective response rate (ORR)(1 year after LPI)
- Health-related quality of life: EORTC QLQ-HCC18(1 year after LPI)
- Exploratory serum biomarker research(1 year after LPI)
研究者
Jian Zhou
Professor of Surgery
Shanghai Zhongshan Hospital