BIBW2992 (Afatinib) in Advanced (EGFR-FISH +) NSCLC (Non Small Cell Lung Cancer) Patients

A Phase II Single-arm Trial of BIBW 2992 in EGFR FISH Positive Non-small Cell Lung Cancer Patients

The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by the RECIST criteria in patients with EGFR FISH positive advanced NSCLC Stage IIIB or IV, selected according to the following scheme:

• Forty (40) 1st line patients
• Thirty (30) 2nd line patients Patients entered into the trial will be treated and followed until death or lost to follow-up. Additional information will be obtained on the safety profile and PK analysis of BIBW 2992.

Inclusion criteria:

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 screening assessments.
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.

Exclusion criteria:

1. More than two (2) prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic NSCLC, included adjuvant chemotherapy if relapse occurred less than 12 months before
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 administration.
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.