'An Open Label, Multicentre, Phase I Study to Evaluate the Impact of Moderate and Severe Hepatic Impairments on the Pharmacokinetics and Safety of Encorafenib in Combination With Binimetinib in Adult Patients With Unresectable or Metastatic BRAF V600-mutant Solid Tumors'.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 7
- 主要终点
- Encorafenib Cmax
研究概览
简要总结
Encorafenib in combination with binimetinib have been approved in USA, Europe, Australia, Japan and Switzerland for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600 mutation.
The main objective of this study is to find a safe and effective dose of encorafenib in combination with binimetinib for patients who have BRAF-mutant metastatic or unresectable melanoma with hepatic dysfunction (i.e. moderate or severe impairment).
详细描述
This is an open label, multicentre, phase I study to evaluate the impact of moderate and severe hepatic impairment (HI) on the pharmacokinetics and safety of encorafenib in combination with binimetinib, in adult patients with unresectable or metastatic BRAF V600-mutant melanoma.
For each participant, the treatment period will be split in 2 phases:
- a HI assessment phase assessing the impact of hepatic impairment after a single dose (Day 1) and after repeated doses (Day 15).
- a post-HI assessment phase: after completing the HI assessment phase, participants may continue treatment in the post-HI assessment phase until disease progression or unacceptable toxicity.
Participants with hepatic impairment will be enrolled sequentially according to their severity. The study will start first in participants with normal hepatic function and moderate hepatic impairment respectively.
Participants will be assigned to one of the following 3 study groups:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group with normal hepatic function
Normal hepatic function
干预措施: Encorafenib + Binimetinib (Drug)
Group with moderate hepatic impairment
Moderate hepatic impairment (Child-Pugh Class B)
干预措施: Encorafenib + Binimetinib (Drug)
Group with severe impairment
Severe impairment (Child-Pugh Class C)
干预措施: Encorafenib + Binimetinib (Drug)
结局指标
主要结局
Encorafenib Cmax
时间窗: Day 1 and Day 15: 0-8 hours post-dose
Maximum Observed Plasma Concentration of encorafenib expressed as total and unbound concentrations
Encorafenib AUC(0-inf)
时间窗: Day 1 and Day 15: 0-8 hours post-dose
Area Under the Plasma Concentration versus Time Curve from Time 0 to Infinity of encorafenib expressed as total and unbound concentrations
Encorafenib AUClast
时间窗: Day 1 and Day 15: 0-8 hours post-dose
Area Under the Plasma Concentration versus Time Curve from Time 0 to Time of Last Quantifiable Concentration of encorafenib expressed as total and unbound concentrations
次要结局
- Tmax(Day 1 and Day 15: 0-8 hours post-dose)
- MRCmax(Derived on Day1 and Day15)
- Cmin(Derived on Day1 and Day15)
- CL/F(Day 1 and Day 15: 0-8 hours post-dose)
- T1/2(Day 1 and Day 15: 0-8 hours post-dose)
- Vz/F(Day 1 and Day 15: 0-8 hours post-dose)
- MRAUC(Derived on Day1 and Day15)