Phase I Open Label Trial to Assess Safety of BIBW 2992 (Afatinib) in Combination With Herceptin® in Patients With HER2-positive Advanced Breast Cancer.
- Registration Number
- NCT00950742
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Study to determine the Maximum Tolerated dose of BIBW 2992 given in combination with Herceptin®
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BIBW 2992 + Trastuzumab BIBW 2992 Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally with fixed weekly infusion doses of 2mg/kg Herceptin. Escalating doses of BIBW 2992 starting at 20mg daily. BIBW 2992 + Trastuzumab Trastuzumab Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally with fixed weekly infusion doses of 2mg/kg Herceptin. Escalating doses of BIBW 2992 starting at 20mg daily.
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLT) 28 days Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Important Limitations and Caveats are provided in the respective section.
Maximum Tolerated Dose (MTD) of Afatinib in Combination With Herceptin(R) 28 days The MTD was defined as the highest dose at which no more than 1 of 6 patients experienced DLT. It was determined using a standard 3 + 3 dose escalation cohort design. To confirm the MTD, the MTD cohort was to be expanded to 18 patients with no more than 3/18 patients experiencing a DLT. Please refer to CAVEATs and Limitations.
- Secondary Outcome Measures
Name Time Method Number of Patients With Objective Response (OR) Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment. Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR).
Progression Free Survival (PFS) Baseline until disease progression, death or data cut-off. PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the response evaluation criteria in solid tumors (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
Summary of Concentration of Herceptin in Plasma 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing Pre-dose Concentrations of Herceptin in Plasma on Days 8, 15 and 29 (Cpre,8, Cpre,15 and Cpre,29) and Maximum Concentration of Herceptin in Plasma on Days 1, 15 and 29 (Cmax,1, Cmax,15 and Cmax,29).
Number of Patients With Best Overall Response Tumor assessment was performed at screening and every 2nd cycle until earliest time of progression, death or end of treatment. Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or not evaluable.
Summary of Concentration of Afatinib in Plasma 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing Pre-dose Concentrations of Afatinib in Plasma at Steady State on Days 8, 15 and 29 (Cpre,ss,8, Cpre,ss,15 and Cpre,ss,29) and Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss).
Time From Dosing to the Maximum Concentration of Afatinib in Plasma at Steady State (Tmax,ss) 0.05 hours (h) before dosing and 0.5-1h, 2h, 3h, 4h, 5h, 6h, 8h after dosing tmax,ss represents the time from dosing to the maximum concentration of afatinib in plasma at steady state
Trial Locations
- Locations (5)
1200.68.44001 Boehringer Ingelheim Investigational Site
🇬🇧Brighton, United Kingdom
1200.68.44003 Boehringer Ingelheim Investigational Site
🇬🇧Cambridge, United Kingdom
1200.68.44005 Boehringer Ingelheim Investigational Site
🇬🇧Guildford, United Kingdom
1200.68.44004 Boehringer Ingelheim Investigational Site
🇬🇧Newcastle upon Tyne, United Kingdom
1200.68.44002 Boehringer Ingelheim Investigational Site
🇬🇧Truro, United Kingdom