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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 4, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Adenocarcinoma Drug: Pemetrexed Drug: BIBW 2992 Drug: Cisplatin Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 345 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : August 2009
Primary Completion Date : January 2012
Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: BIBW 2992
BIBW 2992 tablet once daily until progression
Drug: BIBW 2992
BIBW 2992 once daily until progression
Active Comparator: Cisplatin/Pemetrexed
Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles
Drug: Pemetrexed
Pemetrexed IV given once every 3 weeks for up to 6 cycles
Drug: Cisplatin
Cisplatin IV given once every 3 weeks for up to 6 cycles


Outcome Measures

Primary Outcome Measures :
  1. Progression-free Survival (PFS) Time [ Time Frame: Tumour assessments were performed at screening, Week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks or until death ]
    PFS is defined as time from randomisation to disease progression or death whichever occurs 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. Only data collected until the primary endpoint analysis cut-off date (09 February 2012) were considered.


Secondary Outcome Measures :
  1. Percentage of Patients With Objective Response (OR) [ Time Frame: Tumour assessments were performed at screening, Week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks ]
    OR is defined as complete response (CR) and partial response (PR). Assessed by central independent review according to RECIST 1.1. Only data collected until the primary endpoint analysis cut-off date (09 February 2012) were considered.

  2. Percentage of Participants With Disease Control (DC) [ Time Frame: Tumour assessments were performed at screening, Week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks ]
    DC is defined as a patient with OR or stable disease (SD). Assessed by central independent review according to the RECIST 1.1. Only data collected until the primary endpoint analysis cut-off date were considered.

  3. Overall Survival (OS) Time [ Time Frame: From randomisation to primary endpoint analysis cut-off date. ]
    OS is defined as time from randomisation to death.

  4. Tumour Shrinkage [ Time Frame: Tumour assessments were performed at screening, Week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks ]
    Tumour shrinkage is 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 are presented after adjusting for baseline SoD, EGFR mutation group and race.

  5. Change From Baseline in Body Weight [ Time Frame: Baseline and throughout the trial until progression (every 3 weeks), up to 28 month ]
    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.

  6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [ Time Frame: Throughout the trial until progression (every 3 weeks), up to 28 month ]
    ECOG PS measured on 6 point scale to assess participants 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 selfcare, unable to carry out any work activities; 3=Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours; 4=Completely disabled, cannot carry on any selfcare, totally confined to bed or chair; 5=Dead.

  7. 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 cancerspecific 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.

  8. 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 cancerspecific 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.

  9. 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 cancerspecific 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.

  10. 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 40mg afatinib and after dose escalation to 50 mg or dose reduction to 30mg or 20mg.

  11. 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 40mg afatinib and after dose escalation to 50 mg or dose reduction to 30mg or 20mg.

  12. 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 40mg afatinib and after dose escalation to 50 mg or dose reduction to 30mg or 20mg.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ICH-GCP 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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00949650


  Show 119 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00949650     History of Changes
Other Study ID Numbers: 1200.32
2008-005615-18 ( EudraCT Number: EudraCT )
First Posted: July 30, 2009    Key Record Dates
Results First Posted: November 19, 2013
Last Update Posted: April 4, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Cisplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors