Afatinib (BIBW 2992) QTcF Trial in Patients With Relapsed or Refractory Solid Tumours
- Registration Number
- NCT00875433
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Monotherapy BIBW 2992 BIBW 2992 high dose, once daily, continuous, monotherapy
- Primary Outcome Measures
Name Time Method Objective Response (OR) 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 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.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. PFS was defined as the time from the first treatment to the occurrence of tumour progression or death, whichever came first. It was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas) as well as by the investigators assessment. Median time results from unstratified Kaplan-Meier estimates.
Overall Survival (OS) Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. Overall survival (OS) is defined as time from start of treatment to death.
Disease Control Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. Disease control was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).
Highest CTC Grade for Adverse Events First administration of trial medication until 28 days after last administration of trial medication Highest Common Terminology Criteria (CTC) grade for adverse events
Average Time-matched Heart Rate Change From Baseline to Day 14. The day before the first drug dose (baseline) and the day 14. Average time-matched heart rate change from baseline to day 14.
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 AUC0-24 represents the area under the concentration curve of afatinib in plasma from 0 to 24 hours 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 Cmax represents the maximum measured concentration of afatinib in plasma 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 tmax represents the time from dosing to the maximum concentration of afatinib in plasma 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 AUCtau,ss represents the area under the concentration curve of afatinib in plasma over a uniform dosing interval tau (24h) at steady state (Day14).
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 Cmax,ss represents the maximum measured concentration of afatinib in plasma at steady state (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 tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state (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 R_A,AUC represents the accumulation ratio of AUC values after multiple dose administration over a uniform dosing interval t between days 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 R_A,Cmax represents the accumulation ratio of Cmax values after multiple dose administration over a uniform dosing interval t between days 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 PTF represents the percentage peak trough fluctuation. PTF is defined as difference between maximum and minimum concentration at steady state divided by the average concentration multiplied with 100 to report as percentage.
Duration of Disease Control (DC) Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter. Duration of Disease control (DC). DC was defined as CR, PR or stable disease (SD) and was assessed according to the Macdonald criteria for glioblastomas and brain metastases and according to RECIST for solid tumours (excluding glioblastomas).
Patients With Notable Findings in QTcF on Day 14 Day 14 Notable findings are defined as a QTcF\>500 ms or an increase in QTcF of \>60ms.
Patients With Clinically Relevant Findings in ECG on Day 14 Day 14 Patients with clinically relevant findings in Electrocardiogram data (ECG) on 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 ) Individual QTcF measurements at each time-point. Response was defined as the change from baseline. Analysis adjusted for baseline using a mixed model.
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. Average time-matched QT change from baseline to day 14 over 1 to 24 hours following administration of afatinib.
Patients With Notable Findings in QT on Day 14 Day 14 Number of Patients with notable findings in QT on day 14. Notable findings are defined as a QT\>500 ms.
Trial Locations
- Locations (4)
1200.24.4401 Boehringer Ingelheim Investigational Site
🇬🇧Sutton, United Kingdom
1200.24.4402 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom
1200.24.4403 Boehringer Ingelheim Investigational Site
🇬🇧Guildford, United Kingdom
1200.24.4404 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom