A Phase I Open Label Trial of Continuous Dosing With BIBW 2992 Combined With Paclitaxel and BIBW 2992 Combined With Paclitaxel and Bevacizumab, BIBW 2992 Combined With Carboplatin and BIBW 2992 Combined With Paclitaxel and Carboplatin in Patients With Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 2
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
研究概览
简要总结
The main purpose of this study is to assess the optimum dose of the following medications when they are given together:
- BIBW 2992 and paclitaxel (Taxol)
- BIBW 2992 and paclitaxel and bevacizumab (Avastin)
- BIBW 2992 and carboplatin
- BIBW 2992 and paclitaxel and carboplatin The effect of the different drug combinations will also be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
Part A
BIBW2992 + Paclitaxel
干预措施: BIBW 2992 (Drug)
Part A
BIBW2992 + Paclitaxel
干预措施: Paclitaxel (Drug)
Part B
BIBW2992 + Paclitaxel + Bevacizumab
干预措施: Paclitaxel (Drug)
Part B
BIBW2992 + Paclitaxel + Bevacizumab
干预措施: BIBW2992 (Drug)
Part B
BIBW2992 + Paclitaxel + Bevacizumab
干预措施: Bevacizumab (Drug)
Part C
BIBW2992 + Carboplatin
干预措施: Carboplatin (Drug)
Part C
BIBW2992 + Carboplatin
干预措施: BIBW 2992 (Drug)
Part D
BIBW2992 +Paclitaxel + Carboplatin
干预措施: Carboplatin (Drug)
Part D
BIBW2992 +Paclitaxel + Carboplatin
干预措施: Paclitaxel (Drug)
Part D
BIBW2992 +Paclitaxel + Carboplatin
干预措施: BIBW 2992 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
时间窗: Cycle 1: 21 days (part C and D) or 28 days (part A and B)
Dose limiting toxicity (DLT) was defined as an Adverse Event (AE) or laboratory abnormality considered as related to study treatment.
Maximum Tolerated Dose (MTD)
时间窗: Cycle 1: 21 days (part C and D) or 28 days (part A and B)
The MTD of afatinib in selected combination treatments was defined as the highest dose at which no more than 1 out of 6 patients experienced DLTs during the first treatment cycle, i.e. the highest dose with a DLT incidence ≤17%. The MTD was determined separately for Afatinib in combination with Paclitaxel (part A), Afatinib in combination with Paclitaxel and Bevacizumab (part B), Afatinib and Carboplatin (part C), and Afatinib in combination with Paclitaxel and Carboplatin (part D). In part C, dose escalation was not continued beyond the dose level A40C6, due to safety and pharmacokinetic considerations and upon mutual agreement between the investigators and the sponsor. Formally, no MTD was determined, however a recommended phase II dose was determined and is presented here. 0=not maximum tolerated dose, 1=is maximum tolerated dose Note, the depicted order of treatment groups is driven by dose level, not by the actual dosing steps.
次要结局
- Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15(Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. There were no analyzable patients for Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab.)
- Part B: Afatinib Cmax,ss on Day 15(Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.)
- Incidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade(From first drug administration until the end of treatment cycle 1; 21 days (part C and D) or 28 days (part A and B))
- Part A: Afatinib Cmax,ss on Day 15(Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.)
- Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15(Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.)
- Part A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15(Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.)
- Part A: Paclitaxel Cmax on Day 1 and Day 15(Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.)
- Part B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15(Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.)
- Part B: Paclitaxel Cmax on Day 1 and Day 15(Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.)
- Part C: Afatinib Cmax,ss in Cycle 2(Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.)
- Part B: Bevacizumab Plasma Concentration(Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.)
- Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2(Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.)
- Part C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2(Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00.)
- Part C: Carboplatin Cmax in Cycle 1 and Cycle 2(Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00)
- Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.(Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.)
- Part D: Afatinib Cmax,ss(Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.)
- Part D: Carboplatin Cmax in Cycle 1 and 2(Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.)
- Objective Tumour Response (Unconfirmed)(From first drug administration until the last trial drug administration, up to 1156 days.)
- Objective Tumour Response (Confirmed)(From first drug administration until the last trial drug administration, up to 1156 days.)
- Part D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2(Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 23:00.)
- Part D: Paclitaxel Cmax in Cycle 1 and 2(Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00)
- Part D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2(Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00)