Phase IIb/III randomized, double-blind trial of BIBW 2992 plus best supportive care (BSC) versus placebo plus BSC in non-small cell lung cancer patients failing erlotinib or gefitinib - ND

• Conditions: Patients with confirmed diagnosis of NSCLC; MedDRA version: 9.1Level: LLTClassification code 10061873Term: Non-small cell lung cancer

• Registration Number: EUCTR2007-005983-28-IT
• Lead Sponsor: BOEHRINGER ING.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-15
• Last Update Posted: 14 October 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 480

Inclusion Criteria

-Patients with pathologic confirmation of NSCLC Stage III-B (with pleural effusion) adenocarcinoma or Stage IV adenocarcinoma who have failed at least one but not more than two lines of cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy regimens must have been platinum-based. -Progressive disease following at least 12 weeks of treatment with erlotinib (Tarceva) or gefitinib (Iressa) -Eastern Cooperative Oncology Group (ECOG) performance Score 0, 1 or 2 -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 >=20 mm using conventional techniques or >=10 mm with spiral CT scan -Male and female patients age >=18 years -Life expectancy of at least three (3) months -Written informed consent that is consistent with ICH-GCP guidelines
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-More than two (2) prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic NSCLC. -Use of erlotinib (Tarceva) or gefitinib (Iressa) within 14 days of treatment Day 1 -Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks -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. -Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn?s disease, malabsorption, or CTCAE Grade >2 diarrhea of any etiology at baseline -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 -Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer) -Radiotherapy within the past 2 weeks prior to treatment with the trial drug -History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3 -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 -QTc interval >=0.47 second -Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) >=400 mg/m2 -Absolute neutrophil count (ANC) <=1500 / mm**3 -Platelet count <=100,000 / mm**3 -Bilirubin >=1.5 mg /dl (>26 µmol /L, SI unit equivalent) -Aspartate amino transferase (AST) or alanine amino transferase (ALT) >= three times the upper limit of normal (if related to liver metastases >= five times the upper limit of normal) -Serum creatinine >=1.5 times of the upper normal limit or calculated/measured creatine clearance <=45ml/min -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 -Pregnancy or breast feeding -Patients unable to comply with the protocol -Patients with any serious active infection including known HIV, active hepatitis B or active hepatitis C -Known or suspected active drug or alcohol abuse

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy and safety of BIBW 2992 plus BSC versus placebo plus BSC in a double-blind randomized trial in non-small cell lung cancer patients with progressive disease after at least one but not more than two lines of chemotherapy and at least 12 weeks of treatment with erlotinib or gefitinib;Secondary Objective: 1.) Progression-free survival time 2.) Objective response rate 3.) Duration of clinical benefit 4.) Time to objective response 5.) Duration of objective response 6.) Safety of BIBW 2992 as indicated by intensity and incidence of adverse events 7.) Pharmacokinetics of BIBW 2992 8.) Health-related quality of life (HRQOL) defined as time to deterioration for the three symptoms cough, dyspnea, and pain;Primary end point(s): Overall survival time (OS) will be the primary endpoint defined as the number of days from the date of randomization to the date of death.