Clinical trial NCT00796549: BIBW2992 (Afatinib) in Advanced (EGFR-FISH +) NSCLC (Non Small Cell Lung Cancer) Patients
Official title: A Phase II Single-arm Trial of BIBW 2992 in EGFR FISH Positive Non-small Cell Lung Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-11-24
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
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 EGFR FISH positive advanced NSCLC Stage IIIB or IV, selected according to the following scheme:

* Forty (40) 1st line patients
* Thirty (30) 2nd line patients Patients entered into the trial will be treated and followed until death or lost to follow-up. Additional information will be obtained on the safety profile and PK analysis of BIBW 2992.


Eligibility criteria: Inclusion criteria:

1. Male and female patients aged \>18 years.
2. Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with pleural effusion) or Stage IV and histopathological classification of adeno- or bronchoalveolar carcinoma (BAC).
3. Increased EGFR gene copy number assessed by FISH analysis. After signed informed consent, positive result to EGFR FISH determination is mandatory to proceed to other screening assessments.
4. 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 more or same 20 mm using conventional techniques or moro or same 10 mm with spiral CT scan.
5. Patients not previously exposed to chemotherapy for NSCLC (1st line patients, 40 in total; for these subjects adjuvant chemotherapy is allowed if at least 12 months elapsed since last course of treatment), or patients with relapse after one systemic treatment (2nd line patients, 30 in total; if less than 12 months elapsed since adjuvant chemotherapy, patients are 2nd line ones, as adjuvant chemotherapy must be considered a line of treatment).
6. Life expectancy of at least three (3) months.
7. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0, 1 or 2.
8. Written informed consent that is consistent with ICH-GCP guidelines.

Exclusion criteria:

1. More than two (2) prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic NSCLC, included adjuvant chemotherapy if relapse occurred less than 12 months before
2. Previous treatment with erlotinib (Tarceva®), gefitinib (Iressa®) or any other EGFR inhibiting small molecule or antibody.
3. 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.
4. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks before first drug administration.
5. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn disease, malabsorption, or CTCAE Grade \>2 diarrhea of any etiology at baseline
6. 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.
7. Other malignancies diagnosed within the past five (5) years (other than non melanomatous skin cancer and in situ cervical cancer).
8. Radiotherapy within the past 2 weeks prior to treatment with the trial drug.
9. Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents).
10. Patients with known HIV, active hepatitis B or active hepatitis C.
11. Known or suspected active drug or alcohol abuse.
12. 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.
13. Pregnancy or breast feeding.
14. Patients unable to comply with the protocol.

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 until last response assessment 28NOV12.
Secondary outcomes:
measure: Number of Participants With Objective Response (OR) Categorized by 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 until last response assessment 28NOV12.
measure: Duration of Confirmed Objective Response (OR)
timeFrame: Tumour assessments were performed at baseline (tumour assessment obtained within 4 weeks prior to beginning of treatment), week 8, and every 8 weeks until last response assessment 28NOV12.
measure: Percentage of Participants With Disease Control (DC)
timeFrame: Every 8 weeks until last response assessment 28NOV12
measure: Duration of Confirmed Disease Control
timeFrame: Every 8 weeks until last response assessment 28NOV12
measure: Progression Free Survival (PFS) Time
timeFrame: Every 8 weeks until last response assessment 28NOV12
measure: Overall Survival (OS) Time
timeFrame: Baseline until last vital status assessment 17JUN13
measure: Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 15 (Cpre,ss,15)
timeFrame: Day 15
measure: Number of Participants With Clinical Relevant Finding in Gastrointestinal and Skin Disorder
timeFrame: First administration of trial medication until 28 days after last administration of trial medication, up until 194 weeks
measure: Number of Participants With Clinical Relevant Findings in Laboratory Safety Parameters, Vital Signs and Left Ventricular Ejection Fraction
timeFrame: First administration of trial medication until 28 days after last administration of trial medication, up until 194 weeks
measure: Assessment of Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: End Of Treatment, up until 190 weeks
Other outcomes:
Locations:
city: Arezzo
country: Italy
facility: 1200.40.39011 Boehringer Ingelheim Investigational Site
city: Aviano (PN)
country: Italy
facility: 1200.40.39007 Boehringer Ingelheim Investigational Site
city: Faenza (RA)
country: Italy
facility: 1200.40.39013 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1200.40.39003 Boehringer Ingelheim Investigational Site
city: Livorno
country: Italy
facility: 1200.40.39010 Boehringer Ingelheim Investigational Site
city: Lugo (RA)
country: Italy
facility: 1200.40.39012 Boehringer Ingelheim Investigational Site
city: Modena
country: Italy
facility: 1200.40.39008 Boehringer Ingelheim Investigational Site
city: Monza (MI)
country: Italy
facility: 1200.40.39005 Boehringer Ingelheim Investigational Site
city: Padova
country: Italy
facility: 1200.40.39006 Boehringer Ingelheim Investigational Site
city: Perugia
country: Italy
facility: 1200.40.39002 Boehringer Ingelheim Investigational Site
city: Prato
country: Italy
facility: 1200.40.39004 Boehringer Ingelheim Investigational Site
city: Ravenna
country: Italy
facility: 1200.40.39009 Boehringer Ingelheim Investigational Site
city: Rozzano (MI)
country: Italy
facility: 1200.40.39001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: