BIBW2992 (Afatinib) in Advanced (EGFR-FISH +) NSCLC (Non Small Cell Lung Cancer) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00796549
First received: November 21, 2008
Last updated: December 5, 2013
Last verified: August 2013
  Purpose

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.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: BiBW 2992
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Single-arm Trial of BIBW 2992 in EGFR FISH Positive Non-small Cell Lung Cancer Patients

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Percentage of Participants With Best Objective Response [ Time Frame: Baseline to data cut-off (17 July 2012) ] [ Designated as safety issue: No ]
    Percentage of participants with best objective response: confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0.


Secondary Outcome Measures:
  • Number of Participants With Objective Response (OR) Categorized by Time [ Time Frame: Assessed every 8 weeks from baseline till data cut-off (17 July 2012) ] [ Designated as safety issue: No ]
    Cumulative number of participants with objective response by time points with responders

  • Duration of Confirmed OR [ Time Frame: Baseline to data cut-off (17 July 2012) ] [ Designated as safety issue: No ]
    Duration of confirmed OR is measured from the time of first OR to the time of progression or death (or date of censoring for progression free survival).

  • Percentage of Participants With Disease Control (DC) [ Time Frame: Baseline to data cut-off (17 July 2012) ] [ Designated as safety issue: No ]
    Percentage of participants with OR or stable disease (SD) as determined by RECIST version 1.0.

  • Duration of Confirmed DC [ Time Frame: Baseline to data cut-off (17 July 2012) ] [ Designated as safety issue: No ]
    Duration of DC is measured from the time of first OR to the time of progression or death (or date of censoring for progression free survival) or respectively for SD as the time from date of randomization to date that disease progression.

  • Progression Free Survival (PFS) Time [ Time Frame: Baseline to data cut-off (17 July 2012) ] [ Designated as safety issue: No ]
    PFS time defined as time from the start of treatment to the earliest of progression (RECIST), clinical progression (investigator), start of new anti-cancer treatment or death.

  • Overall Survival (OS) Time [ Time Frame: Baseline to data cut-off (17 July 2012) ] [ Designated as safety issue: No ]
    OS time is defined as time from the date of start of treatment to the date of death.

  • Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 15 (Cpre,ss,15) [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    Cpre,ss,15 represents the pre-dose concentration af afatinib in plasma at steady state on day 15.


Enrollment: 70
Study Start Date: December 2008
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992
BIBW 2992 in EGFR FISH positive NSCLC patients
Drug: BiBW 2992
BIBW 2992 in EGFR FISH positive NSCLC patients

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00796549

Locations
Italy
1200.40.39011 Boehringer Ingelheim Investigational Site
Arezzo, Italy
1200.40.39007 Boehringer Ingelheim Investigational Site
Aviano (PN), Italy
1200.40.39013 Boehringer Ingelheim Investigational Site
Faenza (RA), Italy
1200.40.39003 Boehringer Ingelheim Investigational Site
Genova, Italy
1200.40.39010 Boehringer Ingelheim Investigational Site
Livorno, Italy
1200.40.39012 Boehringer Ingelheim Investigational Site
Lugo (RA), Italy
1200.40.39008 Boehringer Ingelheim Investigational Site
Modena, Italy
1200.40.39005 Boehringer Ingelheim Investigational Site
Monza (MI), Italy
1200.40.39006 Boehringer Ingelheim Investigational Site
Padova, Italy
1200.40.39002 Boehringer Ingelheim Investigational Site
Perugia, Italy
1200.40.39004 Boehringer Ingelheim Investigational Site
Prato, Italy
1200.40.39009 Boehringer Ingelheim Investigational Site
Ravenna, Italy
1200.40.39001 Boehringer Ingelheim Investigational Site
Rozzano (MI), Italy
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00796549     History of Changes
Other Study ID Numbers: 1200.40, 2008-001264-37
Study First Received: November 21, 2008
Results First Received: August 8, 2013
Last Updated: December 5, 2013
Health Authority: Italy: Ethics Committee

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 17, 2014