A Multi-center, Open Label Study to Assess Pharmacokinetics of TKI258 in Adult Cancer Patients With Normal and Impaired Hepatic Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- Pharmacokinetic (PK) parameter of Tmax following a single dose of TKI258 and at the steady state
研究概览
简要总结
This is a multi-center, open label study to assess pharmacokinetics (PK) of TKI258 at single-dose and steady state in adult cancer patients either with mild, moderate or severe hepatic impairment or with normal hepatic function. Hepatic function in study patients will be categorized as normal, mild, moderate or severe based upon pre-dose (Day 1) total bilirubin and AST/ALT levels. Starting dose of TKI258 will depend on total bilirubin and ALT/AST levels at baseline. Patients will be treated until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.
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
- •Patients with histologically or cytologically confirmed solid tumor, excluding breast cancer, that is either refractory to the standard therapy or has no available therapies.
- •ECOG performance status (PS) 0 or 1
- •Patients must have measurable and/or non-measurable lesion(s) as assessed by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI) per RECIST 1.1
排除标准
- •Patients with known brain metastases.
- •Patients who have undergone major surgery ≤ 4 weeks prior to starting study treatment
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
TKI258 normal hepatic function
TKI258 Capsule, @ 500 mg p.o. o.d. 5 days on/2 days off
干预措施: Dovitinib (Drug)
TKI258 mild hepatic impairment
TKI258 capsule @ 500 or 400 mg p.o. o.d. 5 days on/2 days off
干预措施: Dovitinib (Drug)
TKI258 moderate hepatic impairment
TKI258 capsule @ starting dose at 400 mg p.o. o.d. 5 days on/2 days off
干预措施: Dovitinib (Drug)
TKI258 severe hepatic impairment
TKI258 capsule Starting dose to be determined based on the study outcome of the mild and moderate hepatic impairment groups
干预措施: Dovitinib (Drug)
结局指标
主要结局
Pharmacokinetic (PK) parameter of Tmax following a single dose of TKI258 and at the steady state
时间窗: Day 1, Day 19
Tmax will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. Tmax is the time to to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).
Pharmacokinetic (PK) parameter of Cmax following a single dose of TKI258 and at the steady state
时间窗: Day 1, Day 19
Cmax will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. Cmax is the maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).
Pharmacokinetic (PK) parameter of AUClast following a single dose of TKI258 and at steady state
时间窗: Day 1, Day 19
AUClast will be evaluated after a single dose of TKI258 and at the steady state following a 5 days on/2 days off dosing schedule. AUC from time zero to the last measurable concentration sampling time t(last) (mass x time x volume\^-1)
Pharmacokinetic (PK) parameter of AUCinf following a single dose of TKI258
时间窗: Day 1, Day 19
AUCinf is the time to zero to infinity (mass x time x volume)
次要结局
- Change from Baseline in Vital Signs(Baseline, Weeks 1, 4, 5, 9 and once every 8 weeks thereafter)
- Best overall response to anti-tumor activity of TKI258 through imaging as per RECIST 1.1(Every 8 weeks)
- Pharmacokinetics and Hepatic Function Abnormalities(Baseline, every 4 weeks)
- Frequency of Adverse Events and Serious Adverse Events as assessed by Common Terminology Criteria for Adverse Events (CTCAE)(Baseline and every 4 weeks)
- Change from Baseline in Electrocardiogram(Baseline, Weeks 1, 4, 5)