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OpenTrials
Completed

NCT Number: NCT00949650

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

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.

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Key information

Conditions

Carcinoma, Non-Small-Cell Lung Adenocarcinoma 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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Instituto de Medicina Nuclear de Bahía Blanca, Bahía Blanca, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Pemetrexed

Drug

Pemetrexed IV given once every 3 weeks for up to 6 cycles

BIBW 2992

Drug

BIBW 2992 once daily until progression

Cisplatin

Drug

Cisplatin IV given once every 3 weeks for up to 6 cycles

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. Overall Survival (OS) Time

    Time frame: From randomisation to cut-off date (17MAR2017).

    OS was defined as time from randomisation to death.

  4. 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.

  5. 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.

  6. 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.

    • Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work.
    • Ambulatory (>50 percent of waking hours), capable of all self-care, unable to carry out any work activities.
    • Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours.
    • Completely disabled, cannot carry on any self-care, totally confined to bed or chair.
    • 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 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.

  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 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.

  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 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.

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

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

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

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2012
Study completion
2017
First posted
Jul 30, 2009
Registry last updated
Apr 6, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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