Conditions: Carcinoma, Non-Small-Cell Lung
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 171
Healthy volunteers: no

Brief summary:
The primary objective of this trial is to determine the maximum tolerated dose (MTD) and recommended Phase II doses for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib or gefitinib.

Overall safety, pharmacokinetics and anti-tumor activity for the combination of BIBW 2992 and cetuximab in patients with non-small cell lung cancer and acquired resistance to erlotinib, gefitinib or BIBW 2992 will be evaluated as secondary objectives.

Initially a standard, 3+3 dose escalation will be performed to determine the MTD of BIBW 2992 when administered together with cetuximab in patients with advanced non small cell lung cancer and acquired resistance to erlotinib or gefitinib.

Subsequently, the preliminary efficacy and safety of the identified MTD of cetuximab administered with BIBW 2992 will be explored in a combo arm via a further expansion of MTD cohort up to a total of 140 EGFR mutation positive NSCLC with acquired resistance to erlotinib/gefitinib.

Furthermore, the safety and preliminary anti-tumor activity of the combination therapy in EGFR mutant NSCLC patients who developed acquired resistance (AR) to BIBW 2992, will be assessed in a sequential arm. The sequential arm will use a two-stage design with an early stopping rule after 12 patients with acquired resistance to BIBW 2992 have received up to 5 courses of BIBW 2992 plus cetuximab. If no responses are seen in 12 patients during 5 courses of combination therapy, accrual in the sequential arm will stop. If 1 or more responses are observed, the sequential arm will expand up to about 40 patients.

Detailed description:

Arms:
arm 1: patients to receive medium BIBW 2992 once daily plus biweekly cetuximab infusion at low, median and high dose level arm 2: patients to receive BIBW 2992 once daily, upon progression add biweekly cetuximab

Interventions: intervention 1: Cetuximab intervention 2: Cetuximab intervention 3: BIBW 2992 intervention 4: BIBW 2992
Intervention descriptions: intervention 1: BIBW 2992 medium dose plus high dose level of cetuximab intervention 2: BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added intervention 3: BIBW 2992 medium dose plus high dose level of cetuximab intervention 4: BIBW 2992 medium dose monotherapy, upon progression, cetuximab high dose is added

Protocol document: