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Trial record 1 of 1 for:    NCT00949650
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BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

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ClinicalTrials.gov Identifier: NCT00949650
Recruitment Status : Completed
First Posted : July 30, 2009
Results First Posted : November 19, 2013
Last Update Posted : April 6, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE July 29, 2009
First Posted Date  ICMJE July 30, 2009
Results First Submitted Date  ICMJE August 8, 2013
Results First Posted Date  ICMJE November 19, 2013
Last Update Posted Date April 6, 2018
Actual Study Start Date  ICMJE August 14, 2009
Actual Primary Completion Date February 9, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
Progression-Free Survival (PFS) Time [ Time Frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression ]
PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
Original Primary Outcome Measures  ICMJE
 (submitted: July 29, 2009)
The primary endpoint will be progression free survival, as determined by RECIST 1.1. [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2018)
  • Percentage of Patients With Objective Response (OR) [ Time Frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression ]
    OR was defined as Complete Response (CR) or Partial Response (PR). Assessed by central independent review according to RECIST 1.1.
  • Percentage of Participants With Disease Control (DC) [ Time Frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression ]
    DC was defined as a patient with OR or Stable Disease (SD). Assessed by central independent review according to the RECIST 1.1.
  • Overall Survival (OS) Time [ Time Frame: From randomisation to cut-off date (17MAR2017). ]
    OS was defined as time from randomisation to death.
  • Tumour Shrinkage [ Time Frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression ]
    Tumour shrinkage was calculated as the minimum Sum of Diameters (SoD) of target lesions from all post-baseline tumour assessments, as read by the central independent review. The mean of these minimum values were presented after adjusting for baseline SoD, EGFR mutation group and race.
  • Change From Baseline in Body Weight [ Time Frame: Baseline and throughout the trial until progression (every 3 weeks), up to 28 months. ]
    Because the PFS was longer for patients in the Afatinib arm than for patients in the chemotherapy arm, the period of data collection for ECOG status and body weight continued for a longer time in the Afatinib arm.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [ Time Frame: Throughout the trial until progression (every 3 weeks), up to 28 months. ]
    ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction.
    1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work.
    2. Ambulatory (>50 percent of waking hours), capable of all self-care, unable to carry out any work activities.
    3. Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours.
    4. Completely disabled, cannot carry on any self-care, totally confined to bed or chair.
    5. Dead.
  • Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing [ Time Frame: Throughout the trial until progression (every 3 weeks). ]
    HRQOL was measured by European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30 (QLQ-C30) and its lung cancer specific module LC13 (QLQ-LC13). Analysis for cough is based on QLQ-LC13 question 1. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
  • HRQOL: Time to Deterioration in Dyspnoea [ Time Frame: Throughout the trial until progression (every 3 weeks). ]
    HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for dyspnoea is based on composite of QLQ-LC13 questions 3-5. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
  • HRQOL: Time to Deterioration in Pain [ Time Frame: Throughout the trial until progression (every 3 weeks). ]
    HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for pain is based on composite of QLQ-C30 questions 9 and 19. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
  • Trough Plasma Concentrations of Afatinib at Day 22 [ Time Frame: Day 22. ]
    Trough plasma concentrations of Afatinib at Day 22 (course 2, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
  • Trough Plasma Concentrations of Afatinib at Day 29 [ Time Frame: Day 29. ]
    Trough plasma concentrations of Afatinib at day 29 (course 2, visit 2) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
  • Trough Plasma Concentrations of Afatinib at Day 43 [ Time Frame: Day 43. ]
    Trough plasma concentrations of Afatinib at Day 43 (course 3, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2009)
Objective response (CR, PR) and Disease control (CR, PR, SD) according to RECIST 1.1, Overall survival, Deterioration of body weight and ECOG performance status, Health related quality of life (HRQOL), Pharmacokinetics of BIBW 2992, Safety of BIBW 2992 [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation
Official Title  ICMJE A Randomised, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
Brief Summary This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. The objectives of the trial are to compare the efficacy of single agent BIBW 2992, Arm A, with Pemetrexed/Cisplatin chemotherapy, Arm B, as first line treatment for this group of patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma, Non-Small-Cell Lung
  • Adenocarcinoma
Intervention  ICMJE
  • Drug: Pemetrexed
    Pemetrexed IV given once every 3 weeks for up to 6 cycles
  • Drug: BIBW 2992
    BIBW 2992 once daily until progression
  • Drug: Cisplatin
    Cisplatin IV given once every 3 weeks for up to 6 cycles
Study Arms  ICMJE
  • Experimental: BIBW 2992
    BIBW 2992 tablet once daily until progression
    Intervention: Drug: BIBW 2992
  • Active Comparator: Cisplatin/Pemetrexed
    Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles
    Interventions:
    • Drug: Pemetrexed
    • Drug: Cisplatin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 25, 2013)
345
Original Estimated Enrollment  ICMJE
 (submitted: July 29, 2009)
330
Actual Study Completion Date  ICMJE March 16, 2017
Actual Primary Completion Date February 9, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
  • Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material.
  • Measurable disease according to RECIST 1.1.
  • Eastern Cooperative Oncology Group score of 0 or 1.
  • Age >/= 18 years.
  • Life expectancy of at least three months.
  • Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice guidelines.

Exclusion criteria:

  • Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation.
  • Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies.
  • Radiotherapy or surgery (other than biopsy) within 4 weeks prior to randomisation.
  • Active brain metastases
  • Any other current malignancy or malignancy diagnosed within the past five years
  • Known pre-existing interstitial lung disease.
  • Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom.
  • History or presence of clinically relevant cardiovascular abnormalities.
  • Any other concomitant serious illness or organ system dysfunction.
  • Adequate absolute neutrophil count and platelet count
  • Adequate liver and kidney function
  • Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Chile,   France,   Germany,   Hong Kong,   Hungary,   Ireland,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Peru,   Philippines,   Romania,   Russian Federation,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States
Removed Location Countries Mexico
 
Administrative Information
NCT Number  ICMJE NCT00949650
Other Study ID Numbers  ICMJE 1200.32
2008-005615-18 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP