Health Condition 1: null- Stage IIIB or IV metastatic non-small cell lung cancer
Conditions
Interventions
Intervention1: Part A: BIBW 2992 and Part B/Arm 1: BIBW 2992 + weekly paclitaxel: Part A: 50 mg/day BIBW 2992
Part B/Arm 1: 40 mg/day BIBW 2992 + paclitaxel (80 mg/m2)
Control Intervention1: Part B/Ar
Sponsors
Boehringer Ingelheim
Eligibility
Inclusion criteria
Inclusion criteria: 1. Pathologically confirmed diagnosis of NSCLC Stage IIIb (with cytologically proven pleural effusion or pericardial effusion) or Stage IV who have failed treatment with erlotinib (Tarceva®) or gefitinib (Iressa®). 2. Received and failed at least one line of cytotoxic chemotherapy including a platinum-based regimen in patients eligible for platinum-based therapy for advanced or metastatic disease. Exemption: a. Known EGFR mutation shown by accepted methods are eligible after therapy with reversible TKI without prior chemotherapy. or b. Clinical benefit (disease stabilization or anti-tumour response) toerlotinib (Tarceva®) or gefitinib (Iressa®) for ≥6 months are eligiblewithout prior chemotherapy. 3. Eastern Cooperative Oncology Group (ECOG) performance Score 0-2 4. At least one tumour 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 according to RESIST 1.1. 5.Male or female age ≥18 Years. 6.Life expectancy of at least 12 weeks 7.Written informed consent that is consistent with ICH-GCP guidelines.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with BIBW 2992 2. Chemo-, hormone- (other than corticosteroids required for maintenance non-cancer therapy or as premedication before chemotherapy) or immunotherapy within the past 4 weeks, for pretreatment with TKIs (erlotinib (Tarceva®) or gefitinib (Iressa®)) 2 weeks only. 3. Active brain metastases (stable <4 weeks, symptomatic, or leptomeningeal disease. Dexamethasone therapy will be allowed if administered as a stable dose for at least one month before randomization. 4. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn?s disease, mal-absorption, or CTCAE Grade >2 diarrhea of any etiology at baseline. 5. 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. 6. Other malignancies diagnosed (other than non - melanomatous skin cancer and in situ cervical cancer) requiring therapy. 7. Radiotherapy within the past 2 weeks prior to treatment with the trial drug. 8. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) functional classification of 3, unstable angina, or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization. 9. Cardiac left ventricular function with resting ejection fraction of less than 50% measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram. 10. Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) &#8805;400 mg/m2. 11. Absolute neutrophil count (ANC) &#8804;1500/mm3. 12.Platelet count &#8804;100,000/mm3. 13. Bilirubin &#8805;1.5 mg/dL (>26 &#956;mol/L, SI unit equivalent) 14.Aspartate amino transferase (AST) or alanine amino transferase (ALT) &#8805; three times the upper limit of normal (if related to liver metastases &#8805; five times the upper limit of normal). 15. Serum creatinine &#8805;1.5 times the upper normal limit or calculated/measured creatinine clearance &#8804;45 mL/min. 16. 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. 17. Pregnancy or breast feeding. 18. Unable to comply with the protocol. 19. Any serious active infection including known human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C. 20. Known or suspected active drug or alcohol abuse. 21. Pre-existing or current interstitial lung disease (ILD). 22. Peripheral polyneuropathy >Grade 2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall survival (OS) time from the day of randomization until death for patients randomized to either BIBW 2992/paclitaxel combination therapy or comparator chemotherapy.Timepoint: | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.) Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 (R09-0262), separately for Part A and Part B 2.) Clinical benefit rate at 3 months defined as the progression free survival rate at 3 months, separately for Part A and B 3.) Objective response rate (complete response [CR], partial response [PR]) of BIBW 2992 monotherapy according to RECIST 1.1 (R09-0262) 4.) Objective response rate (CR, PR) of BIBW 2992 / paclitaxel combination therapy and comparator chemotherapy in Part B after progression in Part A according to RECIST 1.1 (R09-0262) 5.) Time to objective response, separately for Part A and Part B 6.) HRQOL defined as time to deterioration for the three symptoms cough, dyspnoea, and pain measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13, EQ-5D and QLQ C30 questionnaires.Timepoint: | — |
Countries
Democratic People's Republic of Korea, India
Contacts
Public ContactVinod M
Manipal Acunova
Outcome results
None listed