A phase Ib open label clinical trial of continuous once daily oral treatment usin BIBW 2992 plus cetuximab (Erbitux) in patients with non-small cell lung cancer (NSCLC) with progression following prior erlotinib (Tarceva) or gefitinib (Iressa)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 40

Inclusion Criteria

1. pathologically or cytologically confirmed diagnosis of NSCLC (recurrent, stage IIIB with pleural effusion or IV)
2. Either or both of the following:
- A tumor which harbors an EGFR-mutation known to be associated with drug sensitivity (i.e. G719 X, exon 19 deletion, L858R, L861Q). A tumor which harbors exon 20 insertion or de novo T790M mutation is eligible for the treatment in the sequential arm
-Objective clinical benefit from treatment with an EGFR TKI as defined by either:
a. Documented partial or complete response (RECIST) or
b. stable disease for 6 months (or longer) as defined by RECIST in absence of radiographic progression after initiation of gefitinib or erlotinib; or stable disease/PR/CR >=12 weeks as defined by RECIST after initiation of BIBW 2992
3. Systemic progression of disease (RECIST v1.1) while on continuous treatment with erlotinib or gefitinib or BIBW 2992 within the last 30 days. Patients whose disease progresses only in the central nervous system (CNS) are not eligible.
4. No intervening systemic therapy between cessation of gefitinib or erlotinib or BIBW 2992 and initiation of the treatment in the study.
5. Adequate tumor-derived material such as fresh or archived tumor tissue or pleural fluid from malignant pleural effusion after disease progression on erlotinib/gefitinib/BIBW 2992 must be made available for EGFR mutation analysis.
see for further criteria page 26 of the protocol.

Exclusion Criteria

1. Prior treatment with EGFR targeting antibodies
2. Prior severe infusion reaction to a monoclonal antibody
3. Major surgery within 28 days or minor surgery within 14 days of the start of the study
treatment
4. Radiotherapy less than two weeks prior to the start of the study treatment
6. Less than three days from prior treatment with gefitinib or erlotinib.
7. Symptomatic brain metastases.
8. Other malignancies diagnosed within the past five years unless treated with curative intent. Patients with inactive malignancy may be eligible upon discussion and agreement between investigator and sponsor

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this trial is to determine the maximum tolerated dose<br /><br>(MTD) and recommended Phase II doses for the combination of BIBW 2992 and<br /><br>cetuximab in patients with non-small cell lung cancer and acquired resistance<br /><br>to erlotinib or gefitinib. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>1) Safety of BIBW 2992 when administered together with cetuximab as indicated<br /><br>by intensity and incidence of adverse events, graded according to NCI CTCAE<br /><br>Version 3.0 (R04-0474)<br /><br>2) Pharmacokinetic parameters of BIBW 2992 and cetuximab in the applied<br /><br>treatment setting<br /><br>3) Objective tumor response (Complete Response [CR] and Partial Response [PR])<br /><br>determined by RECIST v1.1)<br /><br>4) Disease control (CR, PR and Stable Disease [SD] determined by RECIST v1.1)<br /><br>5) Progression-free survival (PFS)<br /><br>6) Duration of disease control<br /><br>7) Duration of objective response</p><br>