A Phase II single-arm trial of BIBW 2992 in demographically and genotypically selected non-small cell lung cancer patients - BIBW 2992 in demographically / genotypically NSCLC
- Conditions
- patients with non-small cell lung cancer in stage IIB / IV
- Registration Number
- EUCTR2008-001546-67-BE
- Lead Sponsor
- SCS Boehringer Ingelheim Comm.V
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1.Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with pleural effusion) or Stage IV; histopathological classification of adeno- or bronchoalveolar carcinoma (BAC).
2.non smokers patients or patients having smoked less than 15 pack years and who stopped smoking for at least one year before diagnosis (for cohorts 1 and 2)
3.Presence of activating mutation(s) in exon 18 to exon 21 of the EGFR or HER2-neu-receptor confirmed by direct DNA sequencing of NSCLC tumour tissue (see Section 3.3.3) or increased copy number of the EGFR gene as determined by FISH analysis
4.Prior treatment:
•Cohort 1: progressive disease following therapy with first line EGFR TKI following diagnosis of activating mutation
•Cohort 2: No prior EGFR TKI, up to three lines of chemotherapy (including adjuvant)
•Cohort 3: no restrictions
5.Patients with at least one tumour lesion that can accurately be measured by computed tomography (CT) or magnetic resonance imaging (MRI) in at least one dimension with longest diameter to be recorded as =20 mm using conventional techniques or =10 mm with spiral CT scan.
6.Male or female patient aged =18 years
7.Life expectancy of at least three (3) months.
8.Written informed consents that is consistent with ICH-GCP guidelines.
9.Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0, 1 or 2.
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.More than three (3) prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic NSCLC, except for patients with HER2-neu mutations who may have received any prior therapy
2.Chemo-, hormone- (other than Megace® or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks or within less than four half-lives of the previous drug prior to treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant.
3.Brain metastases, which are symptomatic; patients with treated, asymptomatic brain metastases are eligible with stable brain disease for at least four (4) weeks without the requirement for steroids or anti-epileptic therapy.
4.Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom e.g., Crohn’s disease, malabsorption, or CTCAE Grade >2 diarrhoea of any etiology at baseline
5.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
6.Other malignancies diagnosed within the past five (5) years (other than non melanomatous skin cancer and in situ cervical cancer).
7.Radiotherapy within the past 2 weeks prior to treatment with the trial drug
8.Patients with any serious active infection (i.e., requiring IV antibiotic, antifungal, or antiviral agents).
9.Patients with known HIV, active hepatitis B or active hepatitis C (see Section 5.2.3).
10.Known or suspected active drug or alcohol abuse.
11.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.
12.Pregnancy or breast feeding.
13.Patient unable to comply with the protocol.
14.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.
15.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.
16.Absolute neutrophil count (ANC) less than 1500/mm³.
17.Platelet count less than 100 000 / mm³.
18.Bilirubin greater than 1.5 mg / dl (>26 µmol / L, SI unit equivalent).
19.Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal).
20.Serum creatinine greater than 1.5 times of the upper normal limit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by the RECIST criteria (R01-0754) in patients with advanced NSCLC Stage IIIB or IV whose tumours harbour activating mutations within exon 18 to exon 21 of the EGFR receptor, in patients with mutations in the HER2/neu receptor and in patients with EGFR FISH positive tumours with no EGFR mutations.;Secondary Objective: •Disease control (CR, PR, SD) determined by RECIST (R01-0754)<br>•Progression-free survival time <br>•Pharmacokinetic parameters of BIBW 2992<br>•Safety of BIBW 2992 as indicated by intensity and incidence of adverse events, graded according to NCI CTCAE Version 3.0 (R04-0474) especially skin reactions and GI adverse events<br>;Primary end point(s): The primary endpoint will be objective response (CR, PR) as determined by the RECIST (R01-0754) criteria.
- Secondary Outcome Measures
Name Time Method