Phase II Open Label Trial to Assess the Efficacy and the Impact on QTcF of Continuous Oral BIBW 2992 at a Daily Dose of 50mg in Patients With Relapsed or Refractory Solid Tumours Including Patients With Brain Metastases and Those With Glioblastoma Not Amenable to Other Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Objective Response (OR)
研究概览
简要总结
A phase II trial to assess the impact of afatinib (BIBW 2992) on the heart (QTcF) and the effectiveness of afatinib (BIBW 2992) in treating certain cancers. Cancers studied will include glioblastoma and cancers which have spread to the brain (metastases).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Monotherapy
BIBW 2992 high dose, once daily, continuous, monotherapy
干预措施: BIBW 2992 (Drug)
结局指标
主要结局
Objective Response (OR)
时间窗: Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.
OR is defined as complete response and partial response (PR) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST) for solid tumours (excluding glioblastomas).
Average Time-matched QT Corrected by the Fridericia Formula (QTcF) Change From Baseline to Day 14
时间窗: The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.
Average time-matched QT corrected by the Fridericia formula (QTcF) change from baseline to day 14 over 1 to 24 hours following administration of afatinib.
次要结局
- Progression-free Survival (PFS)(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Overall Survival (OS)(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Disease Control(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Average Time-matched Heart Rate Change From Baseline to Day 14.(The day before the first drug dose (baseline) and the day 14.)
- Highest CTC Grade for Adverse Events(First administration of trial medication until 28 days after last administration of trial medication)
- Area Under Curve 0-24 Hours (AUC0-24) on Day 1(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1)
- Maximum Concentration (Cmax)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1)
- Time From Dosing to the Maximum Concentration (Tmax)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1)
- Area Under Curve of Afatinib Over a Uniform Dosing Interval Tau at Steady State (AUCtau,ss)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14)
- Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14)
- Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14)
- Accumulation Ratio of AUC Values (R_A,AUC)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14)
- Accumulation Ratio of AUC Values (R_A,Cmax)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 1 and 14)
- Percentage Peak Trough Fluctuation (PTF)(0.05 hours (h) before dosing and 1h, 2h, 3h, 4h, 5h, 6h,7h, 10h and 24h after dosing on Day 14)
- Duration of Disease Control (DC)(Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Patients With Notable Findings in QTcF on Day 14(Day 14)
- Patients With Clinically Relevant Findings in ECG on Day 14(Day 14)
- Time-matched QTcF Changes From Baseline to Day 14 at Each Time-point(Baseline and day 14 (at 1, 2, 3, 4, 5, 6, 7, 10, 24 hours post-dose ))
- Average Time-matched QT Change From Baseline to Day 14(The day before the first drug dose (baseline) and the day 14. Electrocardiograms (ECG) were performed at time point 0 and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 10 h, 24 h thereafter.)
- Patients With Notable Findings in QT on Day 14(Day 14)