Study to Determine the Maximum Tolerated Dose of BIBW 2992 (Afatinib) When Combined With Cisplatin/Paclitaxel or Cisplatin/5-FU in Patients With Advanced Solid Tumours
Study to determine the maximum tolerated dose of BIBW 2992 when combined with backbone chemotherapies consisting in cisplatin plus paclitaxel or cisplatin plus 5 FU.
The overall safety, the pharmacokinetics and the anti-tumour efficacy will also be assessed.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase Ib Open Label Study to Assess the Safety, Tolerability and Pharmacokinetics of Continuous Dosing With BIBW 2992 Combined With Two Different Regimens of Backbone Chemotherapy: Cisplatin Combined With 5 Fluorouracil and Cisplatin Combined With Paclitaxel in Patients With Advanced Solid Tumors.|
- Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) [ Time Frame: 21 days ] [ Designated as safety issue: No ]Number of participants with DLT in the first cycle (21 days) for the determination of the MTD.
- Maximum Tolerated Dose (MTD) for Regimen A and Regimen B [ Time Frame: 21 days ] [ Designated as safety issue: No ]The MTD was determined using a standard 3 +3 dose escalation cohort design. The sample size and the number of patients who receive each dose in this design depends on the frequency of DLT at each dose level in cycle 1.
- Number of Patients With Objective Response [ Time Frame: Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days) ] [ Designated as safety issue: No ]Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.0. Objective response is defined as complete response (CR) and partial response (PR).
- Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss) [ Time Frame: 0.05hours (h) before administration and 1h, 2h, 2h 55 minutes (min), 4h, 4h 30min, 5h, 6h, 8h, 10h, 24h, 48h, 216h, 480h after administration ] [ Designated as safety issue: No ]Cmax,ss represents the maximum concentration of afatinib in plasma at steady state
|Study Start Date:||July 2008|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: A. BIBW 2992-cisplatin-paclitaxel
daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-paclitaxel
Drug: BIBW 2992
low to high dose, daily
Experimental: B. BIBW 2992-cisplatin-5FU
daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-5FU
Drug: BIBW 2992
In each arm, BIBW 2992 dose will be escalated to determine MTD. Starting dose will be 20mg daily followed by 40 mg (with the option of an intermediary dose of 30 mg) then 50mg daily. Dose escalation will stop at 50 mg. No intra patient dose escalation.
|1200.37.3202 Boehringer Ingelheim Investigational Site|
|1200.37.3201 Boehringer Ingelheim Investigational Site|
|1200.37.3203 Boehringer Ingelheim Investigational Site|
|Study Chair:||Boehringer Ingelheim||Boehringer Ingelheim|