Clinical trial NCT00730925: Single-arm Trial of BIBW 2992 (Afatinib) in Demographically and Genotypically Selected NSCLC Patients
Official title: A Phase II Single-arm Trial of BIBW 2992 in Demographically and Genotypically Selected NSCLC
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-08-08
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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, 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.


Eligibility criteria: Inclusion criteria:

1. patients with pathologically confirmed diagnosis of NSCLC stage IIIB/IV 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 (except for patients with her2-neu mutation)
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 tumor tissue or increased copy number of the EGFR gene as determined by FISH analysis
4. prior treatment up to 3 lines of chemotherapy except for HER2-neu patients (no restrictions) no prior EGFR TKI therapy for EGFR mutation negative and FISCH positive patients
5. patients with at least one tumor lesion that can accurately be measured by CTscan or MRI in at least one dimension with long diameter to be recorded as \> or equal to 20 mm using conventional techniques or \> or equal to 10 mm with spiral CT scan
6. male or female patient aged above or equal to 18 years
7. life expectancy of at least 3 months
8. written informed consents that is consistent with ICH-GCP guidelines
9. ECOG performance score 0, 1 or 2

Exclusion criteria:

1. more than 3 prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC, except for patients with HER2-neu mutations who may have received any prior therapy
2. Any chemo-, hormone- or immunotherapy within the past 4 weeks or within less than 4 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 4 weeks without requirement for steroids or anti-epileptic therapy
4. 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
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 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 an IV antibiotic, antifungal, or antiviral agents)
9. patients with known HIV, active hepatitis B or active hepatitis C
10. known or suspected active drug or alcohol abuse
11. women of childbearing 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

Primary outcomes:
measure: Percentage of Participants With Best Objective Response
timeFrame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
Secondary outcomes:
measure: Percentage of Participants With Disease Control (DC)
timeFrame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
measure: Progression Free Survival (PFS) Time
timeFrame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks thereafter.
measure: Summary of Pre-dose Concentrations of Afatnib in Plasma
timeFrame: Day 15, 29 and 57
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: 1200.41.32003 Boehringer Ingelheim Investigational Site
city: Charleroi
country: Belgium
facility: 1200.41.32007 Boehringer Ingelheim Investigational Site
city: Jette
country: Belgium
facility: 1200.41.32001 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1200.41.32011 Boehringer Ingelheim Investigational Site
city: Liège
country: Belgium
facility: 1200.41.32008 Boehringer Ingelheim Investigational Site
city: Namur
country: Belgium
facility: 1200.41.32006 Boehringer Ingelheim Investigational Site
city: Badalona (Barcelona)
country: Spain
facility: 1200.41.34001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: De Greve J, Teugels E, Geers C, Decoster L, Galdermans D, De Mey J, Everaert H, Umelo I, In't Veld P, Schallier D. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012 Apr;76(1):123-7. doi: 10.1016/j.lungcan.2012.01.008. Epub 2012 Feb 10.