A Phase II Single-arm Trial of BIBW 2992 in EGFR FISH Positive Non-small Cell Lung Cancer Patients
1. Male and female patients aged >18 years.
2. Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with pleural
effusion) or Stage IV and histopathological classification of adeno- or
bronchoalveolar carcinoma (BAC).
3. Increased EGFR gene copy number assessed by FISH analysis. After signed informed
consent, positive result to EGFR FISH determination is mandatory to proceed to other
4. At least one tumour lesion that can accurately be measured by computed tomography
(CT) or magnetic resonance imaging (MRI) in at least one dimension with longest
diameter to be recorded as more or same 20 mm using conventional techniques or moro
or same 10 mm with spiral CT scan.
5. Patients not previously exposed to chemotherapy for NSCLC (1st line patients, 40 in
total; for these subjects adjuvant chemotherapy is allowed if at least 12 months
elapsed since last course of treatment), or patients with relapse after one systemic
treatment (2nd line patients, 30 in total; if less than 12 months elapsed since
adjuvant chemotherapy, patients are 2nd line ones, as adjuvant chemotherapy must be
considered a line of treatment).
6. Life expectancy of at least three (3) months.
7. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0, 1 or 2.
8. Written informed consent that is consistent with ICH-GCP guidelines.
1. More than two (2) prior cytotoxic chemotherapy treatment regimens for relapsed or
metastatic NSCLC, included adjuvant chemotherapy if relapse occurred less than 12
2. Previous treatment with erlotinib (Tarceva®), gefitinib (Iressa®) or any other EGFR
inhibiting small molecule or antibody.
3. Active brain metastases (stable <4 weeks, symptomatic, requiring treatment with
anticonvulsants, or leptomeningeal disease). Dexamethasone therapy will be allowed if
administered as a stable dose for at least one month before randomization.
4. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance
non-cancer therapy) or immunotherapy within the past 4 weeks before first drug
5. Significant or recent acute gastrointestinal disorders with diarrhea as a major
symptom e.g., Crohn disease, malabsorption, or CTCAE Grade >2 diarrhea of any
etiology at baseline
6. Patients who have any other life-threatening illness or organ system dysfunction
which, in the opinion of the investigator, would either compromise patient safety or
interfere with the evaluation of the safety of the test drug.
7. Other malignancies diagnosed within the past five (5) years (other than non
melanomatous skin cancer and in situ cervical cancer).
8. Radiotherapy within the past 2 weeks prior to treatment with the trial drug.
9. Patients with any serious active infection (i.e., requiring an IV antibiotic,
antifungal, or antiviral agents).
10. Patients with known HIV, active hepatitis B or active hepatitis C.
11. Known or suspected active drug or alcohol abuse.
12. Women of child-bearing potential or men who are able to father a child unwilling to
use a medically acceptable method of contraception during the trial.
13. Pregnancy or breast feeding.
14. Patients unable to comply with the protocol.