BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00949650
First received: July 29, 2009
Last updated: December 5, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Drug: Pemetrexed
Drug: BIBW 2992
Drug: Cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) Time [ Time Frame: From randomisation to primary endpoint analysis cut-off date. ] [ Designated as safety issue: No ]
    OS is defined as time from randomisation to death.

  • Tumour Shrinkage [ Time Frame: Tumour assessments were performed at screening, Week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Body Weight [ Time Frame: Baseline and throughout the trial until progression (every 3 weeks), up to 28 month ] [ Designated as safety issue: No ]
    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 month ] [ Designated as safety issue: No ]
    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.

  • Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing [ Time Frame: Throughout the trial until progression (every 3 weeks) ] [ Designated as safety issue: No ]
    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.

  • HRQOL: Time to Deterioration in Dyspnoea [ Time Frame: Throughout the trial until progression (every 3 weeks) ] [ Designated as safety issue: No ]
    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.

  • HRQOL: Time to Deterioration in Pain [ Time Frame: Throughout the trial until progression (every 3 weeks) ] [ Designated as safety issue: No ]
    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.

  • Trough Plasma Concentrations of Afatinib at Day 22 [ Time Frame: Day 22 ] [ Designated as safety issue: No ]
    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.

  • Trough Plasma Concentrations of Afatinib at Day 29 [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    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.

  • Trough Plasma Concentrations of Afatinib at Day 43 [ Time Frame: Day 43 ] [ Designated as safety issue: No ]
    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.


Enrollment: 345
Study Start Date: August 2009
Estimated Study Completion Date: December 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00949650

  Show 134 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional 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
Study First Received: July 29, 2009
Results First Received: August 8, 2013
Last Updated: December 5, 2013
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Italy: Ethics Committee
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Malaysia: Ministry of Health
Peru: Ministry of Health
Philippines: Bureau of Food and Drugs
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Taiwan: Department of Health
Thailand: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 29, 2014