BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)

Study Overview
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Brief Summary
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This randomized, double-blind, multi-center Phase IIb/III trial will be performed in patients with NSCLC who have received previous treatment with at least one but not more than two lines of cytotoxic chemotherapy (one line must have been a platinum-containing regimen) and either gefitinib or erlotinib for a period of at least 12 weeks and then progressed. The primary objective of this randomized trial is to determine the efficacy of BIBW 2992 as a single agent (Arm A) as compared to a matching placebo (Arm B) in this patient population. Patients on both treatment arms will receive best supportive care in addition to study treatment. Patients enrolled into the trial will be treated and followed until death or lost to follow-up.

Official Title
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Phase IIb/III Randomized, Double-blind Trial of BIBW 2992 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-Lung 1)

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: placebo
* Drug: BIBW 2992


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with pathologic confirmation of NSCLC Stage III-B (with pleural effusion) or Stage IV adenocarcinoma who have failed at least one but not more than two lines of cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy regimens must have been platinum-based. Progressive disease following at least 12 weeks of treatment with erlotinib (Tarceva®) or gefitinib (Iressa®) Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2 Patients with at least one tumor lesion that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in at least one dimension with longest diameter to be recorded as >20 mm using conventional techniques or >10 mm with spiral CT scan Male and female patients age >18 years Life expectancy of at least three (3) months Written informed consent that is consistent with ICH-GCP guidelines Exclusion criteria: Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of treatment Day 1 Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks Active brain metastases Significant or recent acute gastrointestinal disorders with diarrhea Patients who have any other life-threatening illness or organ system dysfunction, Other malignancies diagnosed within the past five (5) years Radiotherapy within the past 2 weeks prior to treatment History of clinically significant or uncontrolled cardiac disease Adequate ANC and platelet count Adequate liver and kidney function Patients with any serious active infection including known HIV, active hepatitis B or active hepatitis C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Patients receive placebo once daily | Drug: placebo<br>* Patients receive placebo once daily<br>|
| Experimental: BIBW 2992<br>Patients receive BIBW 2992 tablets once daily | Drug: BIBW 2992<br>* Patients receive afatinib tablets once daily, and can reduce dose for adverse event management. Afatinib is given once daily, continuously until disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was the duration from the date of randomization to the date of death. Patients who were alive were censored at the last contact date prior to the database lock. For the primary analysis 11 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Primary analysis data cut-off date was 08 July 2010. For the final analysis 13 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Final analysis data cut-off date was 04 October 2013. | From randomization until death or the last patient out date, an average of 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | 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 Tumours version 1.0 (RECIST 1.0). | From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months | 
| Objective Response Rate (OR) | OR is defined as complete response (CR) and partial response (PR). Assessed by central independent review according to RECIST 1.0. | From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months |