A Phase II, Open Label, Single Arm, Multicenter Study of INC280 Administered Orally in Adults With Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Time to Progression (TTP) by Investigator Assessment Per RECIST v1.1
研究概览
简要总结
This study is to find out if INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway.
详细描述
This study is designed as a Phase II, single arm, open-label, multicenter study to evaluate the safety and efficacy of INC280 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for or had disease progression after surgical or locoregional therapies, with c- MET dysregulation.
The study includes a Dose-Determining Part and a Dose Expansion Part. Pharmacokinetic and safety profiles of INC280 in the setting of liver dysfunction will be determined in the Dose-Determining Part. The Dose Expansion Part will start when the appropriate dose for patients with liver dysfunction is determined based on pharmacokinetics (PK) and safety data from the Dose-Determining Part and other INC280 ongoing clinical studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed c-MET pathway dysregulation.
- •Advanced hepatocellular carcinoma which could not be suitable for treatment with locoregional therapies or has progressed following locoregional therapy.
- •Measurable disease as determined by RECIST version 1.
- •Current cirrhotic status of Child-Pugh class A with no encephalopathy.
- •Eastern Cooperative Oncology Group (ECOG) performance status < or =
- •Other protocol-defined inclusion criteria may apply.
排除标准
- •Received any prior systemic chemotherapy or molecular-targeted therapy for hepatocellular carcinoma such as sorafenib.
- •Previous treatment with c-MET inhibitor or hepatocyte growth factor targeting therapy.
- •Previous local therapy completed less than 4 weeks prior to dosing and, if present, any acute toxicity > grade
- •Known active bleeding (e.g. bleeding from gastro-intestinal ulcers or esophageal varices) within 2 months prior to screening or with history or evidence of inherited bleeding diathesis or coagulopathy.
- •Clinically significant venous or arterial thrombotic disease within past 6 months.
- •History of acute or chronic pancreatitis, surgery of pancreas or any risk factors that may increase risk of pancreatitis.
- •Other protocol-defined exclusion criteria may apply.
研究组 & 干预措施
INC280
The protocol consisted of two independent parts (Dose-Determining Part and Dose Expansion Part). Patients were treated with INC280 300 mg twice a day in the Dose-Determining Part. The dose for the Expansion Part could be lower, equal or higher than in the Dose-Determining Part and was determined after the Dose Determining Part at the dose decision analysis.
干预措施: INC280 (Drug)
结局指标
主要结局
Time to Progression (TTP) by Investigator Assessment Per RECIST v1.1
时间窗: Up to approximately 8 years and 2 months
TTP is defined as the time from the date of treatment start to the date of the first documented radiological confirmation of disease progression or death due to underlying cancer. Tumor response was based on investigator assessment per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. For RECIST v1.1, Progressive disease (PD) = At least a 20% increase in the sum of diameters of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. If a patient had not had the event at the date of analysis cut-off or when he/she received any further anti-neoplastic therapy, TTP was censored at the time of the last adequate assessment. TTP was estimated using the Kaplan-Meier method.
次要结局
- Overall Response Rate (ORR) by Investigator Assessment Per RECIST 1.1(Up to approximately 8 years and 2 months)
- Disease Control Rate (DCR) by Investigator Assessment Per RECIST 1.1(Up to approximately 8 years and 2 months)
- Progression-Free Survival (PFS) by Investigator Assessment Per RECIST 1.1(Up to approximately 8 years and 2 months)
- Overall Survival (OS)(Up to approximately 8 years and 2 months)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose of study drug to 30 days after last dose, up to approximately 8 years and 2 months)
- Number of Participants With Dose Reductions and Dose Interruptions of CINC280(From first dose of study drug to last dose, up to approximately 8 years and 1 month)
- Dose Intensity of INC280(From first dose of study drug to last dose, up to approximately 8 years and 1 month)
- Maximum Observed Plasma Concentration (Cmax) of INC280 in the Dose-Determining Part(pre-dose, 30 minutes and 1, 2, 4, 6 and 8 hours after morning dose and 12 hours after evening dose on Cycle 1 Day 1 and Cycle 1 Day 15. The duration of one cycle was 21 days.)
- Time to Reach Maximum Plasma Concentration (Tmax) of INC280 in the Dose-Determining Part(pre-dose, 30 minutes and 1, 2, 4, 6 and 8 hours after morning dose and 12 hours after evening dose on Cycle 1 Day 1 and Cycle 1 Day 15. The duration of one cycle was 21 days.)
- Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours (AUC0-12h) of INC280 in the Dose-Determining Part(pre-dose, 30 minutes and 1, 2, 4, 6 and 8 hours after morning dose and 12 hours after evening dose on Cycle 1 Day 1 and Cycle 1 Day 15. The duration of one cycle was 21 days.)
- Apparent Plasma Clearance (CL/F) of INC280 in the Dose-Determining Part(pre-dose, 30 minutes and 1, 2, 4, 6 and 8 hours after morning dose and 12 hours after evening dose on Cycle 1 Day 1 and Cycle 1 Day 15. The duration of one cycle was 21 days.)
- Terminal Elimination Half-life (T1/2) of INC280 in the Dose-Determining Part(pre-dose, 30 minutes and 1, 2, 4, 6 and 8 hours after morning dose and 12 hours after evening dose on Cycle 1 Day 1 and Cycle 1 Day 15. The duration of one cycle was 21 days.)
- Accumulation Ratio (Racc) of INC280 in the Dose-Determining Part(pre-dose, 30 minutes and 1, 2, 4, 6 and 8 hours after morning dose and 12 hours after evening dose on Cycle 1 Day 1 and Cycle 1 Day 15. The duration of one cycle was 21 days.)