X-Lung 5: BIBW 2992 (afatinib) plus weekly paclitaxel versus investigator's choice of single agent chemotherapy following BIBW 2992 monotherapy in non-small cell lung cancer patients failing erlotinib or gefitinib
- Conditions
- Patients with NSCLC stage IIIb and IV after failure of treatment with erlotinib or gefitinibMedDRA version: 18.0 Level: LLT Classification code 10001164 Term: Adenocarcinoma lung stage III System Organ Class: 100000004864MedDRA version: 18.0 Level: LLT Classification code 10001165 Term: Adenocarcinoma lung stage IV System Organ Class: 100000004864
- Registration Number
- EUCTR2009-014563-39-GB
- Lead Sponsor
- Boehringer Ingelheim Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 1302
Part A:
1. Patients with pathologically confirmed diagnosis of NSCLC Stage IIIb and IV who failed treatment with erlotinib or gefitinib
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 availablility 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 (ECOG) performace score 0-2.
5. Patients with at least one tumour lesion that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in least one dimension with longest diameter to be recorded as >= 10mm but no less than double the slice thickness according to RECIST 1.1
Part B.
1. Clinical benefit of 12 weeks duration in Part A of the trial determined on the second tumour assessment
2. Patients must have progressed in Part A according to RECIST 1.1
3. New informed consent must be signed before patients enter Part B of the trial.
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
1. Previous treatment with BIBW 2992
2. Chemo-, hormone or immunotherapy within the past 4 weeks.For pretreatment with TKIs (erlotinib(Tarceva) or gefitinib (Iressa)) 2 weeks only.
3. Active/symptomatic brain metastases including leptomeningeal disease. Patients with a history of treated brain metastatis must have a stable or normal brain MRI/CT scan at screening and be at least 4 weeks post-radiation or surgery for brain metastasis. Dexamethasone therapy will be allowed only if administered at a stable dose for at least one month prior to randomization.
4. Patients who have any other life-threatening illness or organ system dysfunction
5. Other malignancies diagnosed requiring therapy
6. History or presence of clinically relevant cardiovascular abnormalities
6. Cardiac left ventricular function with resting ejection fraction of less than 50%
The rest of the other points to 22 and the new point 23 have been included:
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) =400 mg/m2
11) Absolute neutrophil count (ANC) =1500/mm3
12) Platelet count =100,000/mm3
13) Bilirubin =1.5 mg/dL (>26 µmol/L, SI unit equivalent)
14) 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)
15) Serum creatinine =1.5 times the upper normal limit or calculated/measured creatinine clearance =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 >Grade 2
23) Requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2.1
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective is to determine the efficacy of BIBW 2992 plus weekly paclitaxel compared to Investigator`s choice of chemotherapy alone in patients with NSCLC stage IIIb or IV progressing after a benefit from BIBW 2992 montherapy.;Secondary Objective: Gaining information on safety and health-related quality of life separately for Part A and B;Primary end point(s): The primary endpoint is the progression free survival (PFS) time from the day of randomization until progression as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for patients randomized to either BIBW 2992/paclitaxel combination therapy or comparator chemotherapy.
- Secondary Outcome Measures
Name Time Method