BIBW 2992 Plus Simvastatin vs. BIBW 2992 in Previously Treated Patients With Advanced Non-adenocarcinomatous NSCLC

Inclusion Criteria:

1. Pathologically confirmed diagnosis of Stage IIIB or Stage IV non-adenocarcinomatous non-small cell lung cancer (e.g., squamous cell or large cell carcinoma).(The 7th edition of the TNM classification for lung cancer47-See Appendix 6)
2. Progressive disease following the first or second line cytotoxic chemotherapy regimen(s) including at least one platinum-containing regimen.
3. Measurable disease according to RECIST 1.1.40
4. Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2.41
5. Age ≥ 18 years.
6. Life expectancy of at least three (3) months.
7. Written informed consent that is consistent with ICH-GCP guidelines.

Exclusion Criteria:

1. More than three (3) prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC.
2. Prior treatment with EGFR targeting small molecules or antibodies (e.g., gefitinib, erlotinib, cetuximab).
3. Chemotherapy, hormonal therapy (other than megestrol acetate or steroids required for maintenance non-cancer therapy), immunotherapy or surgery (other than biopsy) within 4 weeks prior to study entry.
4. Radiotherapy within 2 weeks prior to study entry. Only palliative radiotherapy to non-target lesion should be allowed for the entered cases.
5. Active brain metastases with clinically significant neurological symptoms or signs. Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs.
6. Any other current malignancy or malignancy diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
7. Known pre-existing interstitial lung disease.
8. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTC grade ≥2 diarrhea of any etiology.
9. Absolute neutrophil count (ANC) \<1500 / mm3.
10. Platelet count \< 100,000 / mm3.
11. Serum creatinine \>1.5 times upper limit of normal (ULN) or creatinine clearance \< 60 ml / min
12. Bilirubin \> 1.5 times upper limit of normal.
13. Aspartate amino transferase (AST) or alanine amino transferase (ALT) \> 3 times the upper limit of normal (ULN) (if related to liver metastases \> 5 times ULN).
14. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to study entrance.
15. Cardiac left ventricular function with resting ejection fraction of less than 50%.
16. Any other concomitant serious 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.
17. Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial.
18. Pregnancy or breast-feeding.
19. Patients unable to comply with the protocol.
20. Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
21. Known or suspected active drug or alcohol abuse.
22. Requirement for treatment with any of the prohibited concomitant medications listed in Section 4.2.2.
23. Any contraindications for therapy with simvastatin.
24. Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
25. Use of any investigational drug within 4 weeks of randomization (unless a longer time period is required by local regulations).