Phase I Safety and Pharmacokinetic Study of XRP6258 (Cabazitaxel) In Advanced Solid Tumor Patients With Varying Degrees of Hepatic Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 56
- 试验地点
- 14
- 主要终点
- Incidence of Dose Limiting Toxicities (DLT)
研究概览
简要总结
Primary Objectives:
- To determine the maximum tolerated dose (MTD) and safety of Cabazitaxel when administered to advanced solid tumor patients with varying degrees of hepatic impairment
- To determine the pharmacokinetics (PKs) of Cabazitaxel in patients with varying degrees of hepatic impairment
- To correlate PK variables with pharmacodynamic (PD) safety parameters in order to guide prescribers with regard to dosing in this patient population
- To assess the effect of cabazitaxel at recommended dose of 25mg/m^2 on CYP3A enzyme activity using midazolam as probe in an additional cohort of cancer patients with normal hepatic function.
详细描述
The study consists of:
- a screening phase (maximum length of 21-day).
- a treatment phase with 21-day study treatment cycles. Cycle lengths may be extended up to maximum of 12 additional days in case of unresolved toxicity.
Patients continue to receive treatment until they experience, unacceptable toxicities/AEs, disease progression ,withdraw their consent, or the investigator decides to discontinue the patient, or study cut-off, whichever comes first.
- a 30-day follow-up visit after the last dose of study medication.
The cut off date is when the last patient treated has completed cycle 1 and the subsequent 30 days follow-up.
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 60 Years（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
Cohort 1: normal hepatic function: cabazitaxel
cabazitaxel 25mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).
干预措施: Cabazitaxel (XRP6258) (Drug)
Cohort 2: mild hepatic impairment : cabazitaxel
cabazitaxel 20mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).
干预措施: Cabazitaxel (XRP6258) (Drug)
Cohort 3: moderate hepatic impairment: cabazitaxel
cabazitaxel 10mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).
干预措施: Cabazitaxel (XRP6258) (Drug)
Cohort 4: severe hepatic impairment: cabazitaxel
cabazitaxel 5 mg/m^2 or 10mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).
干预措施: Cabazitaxel (XRP6258) (Drug)
Cohort 5: normal hepatic function: cabazitaxel and midazolam
cabazitaxel 25mg/m^2
IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).
Midazolam is given orally in single dosing on day -1 and day 1 (crossover)
干预措施: Cabazitaxel (XRP6258) (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLT)
时间窗: cycle 1 (3 weeks)
A clinical adverse event or a laboratory abnormality is defined as DLT when it is drug-related as assessed by the investigator and agreed upon by the study committee.
次要结局
- Safety investigations (physical examination, vital signs and laboratory tests)(up to 30 days after the last dosing)
- Cabazitaxel effect on CYP3A enzyme activity(single dosing on day -1 and day 1)
- Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration(cycle 1 (3 weeks))