Phase III Randomized Trial of BIBW 2992 Plus Weekly Paclitaxel Versus Investigator's Choice of Chemotherapy Following BIBW 2992 Monotherapy in Non-small Cell Lung Cancer Patients Failing Previous Erlotinib or Gefitinib Treatment (LUX Lung 5)
1. Patients with 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. Patients should have received and failed at least one line of cytotoxic chemotherapy
including a platinum-based regimen in patients eligible for platinum-based therapy
and pemetrexed in pemetrexed eligible patients (unless pemetrexed is not considered a
regulatory or clinical standard of care e.g. no label indication, no availability or
no coverage by 3rd party payer(s)) for advanced or metastatic disease and have
progressive disease following at least 12 weeks of treatment with erlotinib or
3. Patients pretreated with taxane-based chemotherapy for advanced or metastatic disease
must have experienced stable disease, partial or complete response as best response
4. Eastern Cooperative Oncology Group performance Score 0 or 1.
5. 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 10 mm but no less than double the slice thickness
according to RESIST 1.1.
6. Male and female patients no less than 18 years of age.
7. Life expectancy of at least three (3) months.
8. Written informed consent that is consistent with ICH-GCP guidelines. Part B 1)
Clinical benefit (disease stabilization or antitumor response) of 12 weeks duration
in Part A of the trial determined on the second tumour assessment.
2.) Patients should have progressed in Part A according to RECIST 1.1 3.) New informed
consent, including consent to biomarker sampling, must be signed before patients enter
Part B of the trial
1. Chemo-, hormone- (other than megestrol acetate, steroids required for maintenance
non-cancer therapy or as premedication before chemotherapy) or immunotherapy within
the past 4 weeks; except for TKI pretreatment (2 weeks only)
2. Active/symptomatic brain metastases including leptomeningeal disease. Patients with a
history of treated brain metastasis must have a stable or normal brain MRT/CT scan at
screening and be at least 4 weeks post-radiation or surgery for brain metastasis.
Dexamethasone therapy will be allowed if administered as a stable dose for at least
one month before randomization.
3. 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
4. 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
5. Other malignancies diagnosed within the past five (5) years (other than
non-melanomatous skin cancer and in situ cervical cancer)
6. Radiotherapy within the past 2 weeks prior to treatment with the trial drug
7. 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.
8. 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
9. Requirement for treatment with any of the prohibited concomitant medications listed
in section 126.96.36.199
10. Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or
equivalent) at or greater than 400 mg/m2
11. Absolute neutrophil count (ANC) at or less than 1500 / mm3
12. Platelet count at or less than 100,000 / mm3
13. Bilirubin at or greater than 1.5 mg / dL (>26 mol / L, SI unit equivalent)
14. Aspartate amino transferase (AST) or alanine amino transferase (ALT) at or greater
than three times the upper limit of normal (if related to liver metastases at or
greater than five times the upper limit of normal)
15. Serum creatinine at or greater 1.5 times the upper normal limit or
calculated/measured creatinine clearance at or less than 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. Patients unable to comply with the protocol
19. Patients with 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 of > Grade 2