Trial Exploring Afatinib (BIBW 2992) + Paclitaxel (Part A), Afatinib + Paclitaxel + Bevacizumab (Part B), Afatinib + Carboplatin (Part C) and Afatinib+ Paclitaxel +Carboplatin(Part D) in Patients With Advanced Solid Tumours
- Conditions
- Neoplasms
- Interventions
- Registration Number
- NCT00809133
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 83
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Part A BIBW 2992 BIBW2992 + Paclitaxel Part D BIBW 2992 BIBW2992 +Paclitaxel + Carboplatin Part B BIBW2992 BIBW2992 + Paclitaxel + Bevacizumab Part C BIBW 2992 BIBW2992 + Carboplatin Part A Paclitaxel BIBW2992 + Paclitaxel Part B Paclitaxel BIBW2992 + Paclitaxel + Bevacizumab Part B Bevacizumab BIBW2992 + Paclitaxel + Bevacizumab Part C Carboplatin BIBW2992 + Carboplatin Part D Carboplatin BIBW2992 +Paclitaxel + Carboplatin Part D Paclitaxel BIBW2992 +Paclitaxel + Carboplatin
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) 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) 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.
- Secondary Outcome Measures
Name Time Method 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. Area under the concentration-time curve of Afatinib in plasma at steady state.
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. Maximum measured concentration of Afatinib in plasma at steady state.
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) Incidence and Intensity of AEs (Adverse Events) graded according to the maximum CTCAE (Common Toxicity Criteria for Adverse Events) grade based on the number of patients with AEs with CTCAE Grade 1-5.
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. Maximum measured concentration of Afatinib in plasma at steady state.
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. Area under the concentration-time curve of Afatinib in plasma at steady state.
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. AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.
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. Maximum measured concentration of Paclitaxel in plasma.
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. AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours.
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. Maximum measured concentration of Paclitaxel in plasma.
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. Maximum measured concentration of Afatinib in plasma at steady state.
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. Bevacizumab plasma concentration after infusion of Bevacizumab 5mg/kg after end of 1st and 2nd infusion in Cycle 1.
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. AUCt,ss: Area under the concentration-time curve of Afatinib in plasma at steady state.
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. AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.
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 Maximum measured concentration of Carboplatin in plasma.
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. AUCt,ss: Area under the concentration-time curve of Afatinib at steady state.
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. Maximum measured concentration of Afatinib in plasma at steady state.
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. Maximum measured concentration of Carboplatin in plasma.
Objective Tumour Response (Unconfirmed) From first drug administration until the last trial drug administration, up to 1156 days. Number of subjects with objective tumour response (unconfirmed).
Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR).Objective Tumour Response (Confirmed) From first drug administration until the last trial drug administration, up to 1156 days. Number of subjects with confirmed objective tumour response.
Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR). Objective response was to be confirmed by a second tumour assessment at least 4 weeks after the assessment of CR or PR.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. AUC0-23: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 23 hours.
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 Maximum measured concentration of Paclitaxel in plasma.
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 AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours.
Trial Locations
- Locations (2)
1200.12.4401 Boehringer Ingelheim Investigational Site
🇬🇧Sutton, United Kingdom
1200.12.4402 Boehringer Ingelheim Investigational Site
🇬🇧London, United Kingdom