Overview

This trial is active, not recruiting.

Condition carcinoma, non-small-cell lung
Treatments investigator´s choice of chemotherapy, bibw 2992
Phase phase 3
Targets EGFR, HER2, HER4
Sponsor Boehringer Ingelheim
Start date February 2010
End date October 2013
Trial size 1302 participants
Trial identifier NCT01085136, 1200.42, 2009-014563-39

Summary

The primary objective of this randomized, open-label, active-controlled, multi-center trial is to determine the efficacy of BIBW 2992 given as an add-on to chemotherapy in patients with NSCLC Stage IIIb or IV progressing after BIBW 2992 monotherapy compared to chemotherapy alone in this patient population. Patients on both treatment arms will receive best supportive care in addition to study treatment. Patients enrolled into the trial will be treated and followed until death or lost to follow-up. Additional information on the health-related quality of life (HRQOL) will be collected.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Patients will be treated with investigator`s choice of chemotherapy
investigator´s choice of chemotherapy
BIBW 2992 in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy
(Experimental)
Patients will be treated with BIBW 2992 daily with a medium dose and weekly administration of Paclitaxel at a dose of 80 mg/m2
bibw 2992
BIBW 2992 will be given in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy

Primary Outcomes

Measure
Progression Free Survival (PFS) Time as Determined by RECIST 1.1 for Part B.
time frame: Every 8 weeks until the final follow-up visit in Part B, up to a total of 10 years.

Secondary Outcomes

Measure
Progression Free Survival (PFS) as Determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A
time frame: tumour assessment was at screening (-28 days to screening) and every 6 weeks until the first follow-up visit in Part A, up to a total of 10 years.
Overall Survival (OS) as Determined by the Time From Randomization to Death in Part B
time frame: from the date of randomisation to the date of death, up to a total of 10 years.
Objective Response Rate According to RECIST 1.1 in Part B
time frame: tumour assessment was every 8 weeks until the final follow-up visit in Part B, up to a total of 10 years.
Objective Response According to RECIST 1.1 in Part A
time frame: tumour assessment was at screening (-28 days to screening) and every 6 weeks until the first follow-up visit in Part A, up to a total of 10 years.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria: Part A 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 gefitinib 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 Exclusion criteria: 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 4.2.2.1 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

Additional Information

Official title 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)
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.