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

March 9, 2018 updated by: Boehringer Ingelheim

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

345

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Bahía Blanca, Argentina, B8000FJI
        • Instituto de Medicina Nuclear de Bahía Blanca
      • Capital Federal, Argentina, C1118AAT
        • Hospital Aleman
      • Capital Federal, Argentina, C1185AAT
        • Imcaba S.R.L.
      • Capital Federal, Argentina, C1425AWC
        • IMAI Research
      • Capital Federal, Argentina, C1426ANZ
        • Instituto Alexander Fleming
      • Capital Federal, Argentina, C1426BOR
        • Hospital Militar Central
      • Capital Federal, Argentina, C1430ERF
        • Paliar
      • Rosario, Argentina, S2000KZE
        • Centro Oncologico de Rosario
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Lifehouse
      • St Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
      • Waratah, New South Wales, Australia, 2298
        • Calvary Mater Newcastle Hospital
    • Queensland
      • Chermside, Queensland, Australia, 4032
        • The Prince Charles Hospital
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
      • Toorak Gardens, South Australia, Australia, 5065
        • The Burnside War Memorial Hospital
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital
      • Fitzroy, Victoria, Australia, 3065
        • St. Vincents Hospital (MEL)
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Mount Medical Centre
  • Austria
      • Linz, Austria, 4010
        • KH d. Elisabethinen Linz
      • Wels, Austria, 4600
        • Klinikum Wels - Grieskirchen GmbH
      • Wien, Austria, 1140
        • SMZ Baumgartner Hoehe Otto Wagner Spital
  • Belgium
      • Bruxelles, Belgium, 1000
        • Brussels - UNIV St-Pierre
      • Gent, Belgium, 9000
        • UNIV UZ Gent
      • Jette, Belgium, 1090
        • Brussels - UNIV UZ Brussel
      • Leuven, Belgium, 3000
        • UZ Leuven
      • Liège, Belgium, 4000
        • Centre hospitalier universitaire de Liege
  • Brazil
      • Belo Horizonte, Brazil
        • Centro de Pesquisa do Hospital Lifecenter
      • Cachoeiro de Itapemirim, Brazil, 29308-014
        • Centro de Pesquisas Clinicas em Oncologia
      • Curitiba, Brazil, 80530-010
        • Insituto de Oncologia do Paraná
      • Porto Alegre, Brazil, 90610-000
        • Hospital São Lucas da Pontifícia Universidade Católica
      • Sao Paulo, Brazil, 04023-900
        • UNIFESP Departamento de Medicina de Pneumologia
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute (University of Alberta)
    • Migration Data
      • Greenfield Park, Migration Data, Canada, J4V 2H1
        • Charles LeMoyne Hospital
      • Montreal, Migration Data, Canada, H2L 4M1
        • Hematologiste et oncologue medical CHUM - Hopital Notre-Dame
      • Montreal, Migration Data, Canada, H2W 1S6
        • McGill University, Department of Oncology
  • Chile
      • Los Condes, Chile, 760-0746
        • Hospital Dirección de Previsión de Carabineros
      • Reñaca, Chile, 2540364
        • Instituto Oncológico Limitada Viña del Mar
      • Temuco, Chile
        • Instituto Clínico Oncológico del Sur - ICOS
  • France
      • Angers, France, 49933
        • HOP d'Angers
      • Caen Cedex 5, France, 14033
        • HOP Côte de Nacre
      • La Tronche, France, 38700
        • HOP Nord Michallon
      • Lyon Cedex 4, France, 69317
        • HOP Croix Rousse, Pneumo, Lyon
      • Paris Cedex 05, France, 75248
        • INS Curie
      • Saint Herblain, France, 44805
        • CTR René Gauducheau
      • Saint Pierre - La Réunion, France, 97448
        • HOP Sud-Réunion, Pneumo, Saint Pierre
      • Toulon, France, 83041
        • HOP - HIA Sainte Anne
      • Villefranche Sur Saône, France, 69655
        • HOP, Pneumo, Villefranche sur Saône
  • Germany
      • Berlin, Germany, 12200
        • Universitätsklinikum Benjamin Franklin, Berlin
      • Essen, Germany, 45122
        • Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
      • Hemer, Germany, 58675
        • Lungenklinik Hemer
      • Mainz, Germany, 55101
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
      • Münster, Germany, 48149
        • Universitätsklinikum Münster
      • Oldenburg, Germany, 26121
        • Pius-Hospital, Oldenburg
      • Taipei, Germany, 100
        • National Taiwan University Hospital
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
      • Shatin, Hong Kong
        • Prince of Wales Hospital
  • Hungary
      • Szekesfehervar, Hungary, 8000
        • Szent György Hospital, Szekesfehervar
      • Szombathely, Hungary, 9700
        • Markusovszky County Hospital, Szombathely
      • Zalaegerszeg, Hungary, 8900
        • Zala County Hospital, Zalaegerszeg
  • Ireland
      • Dublin 8, Ireland
        • St James's Hospital
  • Italy
      • Arezzo, Italy, 52100
        • Ospedale San Donato di Arezzo
      • Prato, Italy, 59100
        • Az. USL 4 di Prato
      • Roma, Italy, 00189
        • Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
      • Sant'Andrea Delle Fratte (PG), Italy, 06132
        • Osp. Silvestrin
  • Japan
      • Aichi, Nagoya, Japan, 464-8681
        • Aichi Cancer Center Hospital
      • Aichi, Nagoya, Japan, 460-0001
        • National Hospital Organization Nagoya Medical Center
      • Chiba, Kashiwa, Japan, 277-8577
        • National Cancer Center Hospital East
      • Ehime, Matsuyama, Japan, 791-0280
        • National Hospital Organization Shikoku Cancer Center
      • Fukuoka, Fukuoka, Japan, 811-1395
        • National Hospital Organization Kyushu Cancer Center
      • Hokkaido, Sapporo, Japan, 060-8648
        • Hokkaido University Hospital
      • Hyogo, Kobe, Japan, 650-0047
        • Institute of Biomedical Research and Innovation Hospital
      • Ishikawa, Kanazawa, Japan, 920-8641
        • Kanazawa University Hospital
      • Kanagawa, Yokohama, Japan, 236-0051
        • Kanagawa Cardiovascular and Respiratory Center
      • Niigata, Niigata, Japan, 951-8566
        • Niigata Cancer Center Hospital
      • Okayama, Kurashiki, Japan, 710-8602
        • Kurashiki Central Hospital
      • Okayama, Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Osaka, Osaka, Japan, 534-0021
        • Osaka City Hospital Organization Osaka City General Hospital
      • Osaka, Osaka-Sayama, Japan, 589-8511
        • Kindai University Hospital
      • Sakai, Osaka, Japan, 591-8555
        • National Hospital Organization Kinki-chuo Chest Medical Center
      • Shizuoka, Sunto-gun, Japan, 411-8777
        • Shizuoka Cancer Center
  • Korea, Republic of
      • Cheongju, Korea, Republic of, 361-771
        • Chungbuk National University Hospital
      • Hwasun, Korea, Republic of, 519-763
        • Chonnam National University Hwasun Hospital
      • Seongnam, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center
      • Ulsan, Korea, Republic of, 682-714
        • Ulsan University Hospital
  • Malaysia
      • Palau Pinang, Malaysia, 10990
        • Hospital Pulau Pinang
      • Wilayah Persekutuan, Malaysia, 5600
        • Pusat Perubatan University Kebangsaan Malaysia
      • Wilayah Persekutuan, Malaysia, 59100
        • University Malaya Medical Centre
  • Peru
      • La Victoria, Peru
        • Hospital Nacional Guillermo Almenara Irigoyen
      • San Isidro, Peru, 27
        • Clínica Anglo Americana
      • Surquillo, Peru, 34
        • Instituto Nacional de Enfermedades Neoplasicas
  • Philippines
      • Cebu City, Philippines, 6000
        • Perpetual Succour Hospital (Cebu)
      • Makati City, Philippines, 1229
        • Makati Medical Center
      • Quezon, Philippines, 1102
        • St. Luke Medical Centre
  • Romania
      • Cluj Napoca, Romania, 400015
        • Institutul Oncologic "Prof. Dr. Ion Chiricuta"
      • Craiova, Romania, 200535
        • ONCOLAB SRL, Craiova
  • Russian Federation
      • Kazan, Russian Federation, 420029
        • Republic Clinical Oncology Dispensary, Dept. Chemotherapy
      • Moscow, Russian Federation, 115478
        • FSBSI "N.N Blokhin Medical Research Center of Oncology"
      • Obninsk, Russian Federation, 249020
        • Medical Radiology Science Centre
      • St. Petersburg, Russian Federation, 197758
        • FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
      • St. Petersburg, Russian Federation, 197022
        • SPb SBIH "City Clinical Oncological Dispensary"
      • St. Petersburg, Russian Federation, 197022
        • First Pavlov State Medical University Saint Petersburg
  • Taiwan
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Kaohsiung, Taiwan, 833
        • Chang Gung Memorial Hospital Kaohsiung
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Tainan, Taiwan, 704
        • NCKUH
      • Taipei, Taiwan, 114
        • Tri-Service General Hospital
      • Taipei, Taiwan, 112
        • Taipe Veterans General Hospital
      • Taoyuan, Taiwan, 33305
        • Chang Gung Memorial Hospital(TaoYuan)
  • Thailand
      • Bangkok, Thailand, 10400
        • Ramathibodi Hospital
      • Chiang Mai, Thailand, 50200
        • Maharaj Nakorn Chiang Mai Hospital
      • Khonkaen, Thailand, 40002
        • Srinagarind Hospital
      • Songkla, Thailand, 90110
        • Songklanagarind Hospital
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
        • City Clinical Hospital #4, Dnipropetrovsk State Medical Academy
      • Donetsk, Ukraine, 83000
        • Donetsk Regional Antitumor Centre
      • Kharkiv, Ukraine, 16070
        • Kharkiv Regional Clinical Oncology Center
      • Lviv, Ukraine, 79031
        • Lviv State Oncological Regional Treatment & Diagnostic CTR
  • United Kingdom
      • Exeter, United Kingdom, EX2 5DW
        • Royal Devon and Exeter Hospital
      • Guildford, United Kingdom, GU2 7XX
        • Royal Surrey County Hospital
      • London, United Kingdom, SW3 6JJ
        • the Royal Marsden Hospital
      • Maidstone, United Kingdom, ME16 9QQ
        • Maidstone Hospital, Kent Oncology Centre
      • Scunthorpe, United Kingdom, DN15 7BH
        • Scunthorpe General Hospital, Oncology
      • Sutton, United Kingdom, SM2 5PT
        • the Royal Marsden Hospital
      • Truro, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospital
  • United States
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group
    • California
      • Montebello, California, United States, 90640
        • Clinical Trials and Research Associates Inc
    • Florida
      • Miami, Florida, United States, 33179
        • Innovative Medical Research of South Florida
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • Crescent City Research Consortiom
    • New York
      • Rochester, New York, United States, 14623
        • Interlakes Foundation, Incorporated
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital / Lehigh Valley Health Network
    • Texas
      • Corpus Christi, Texas, United States, 78410
        • South Texas Institute of Cancer, Northwest Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
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.
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Overall Survival (OS) Time
Time Frame: From randomisation to cut-off date (17MAR2017).
OS was defined as time from randomisation to death.
From randomisation to cut-off date (17MAR2017).
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.
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
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.
Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
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.
Throughout the trial until progression (every 3 weeks), up to 28 months.
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.
Throughout the trial until progression (every 3 weeks).
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.
Throughout the trial until progression (every 3 weeks).
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.
Throughout the trial until progression (every 3 weeks).
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.
Day 22.
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.
Day 29.
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.
Day 43.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 14, 2009

Primary Completion (Actual)

February 9, 2012

Study Completion (Actual)

March 16, 2017

Study Registration Dates

First Submitted

July 29, 2009

First Submitted That Met QC Criteria

July 29, 2009

First Posted (Estimate)

July 30, 2009

Study Record Updates

Last Update Posted (Actual)

April 6, 2018

Last Update Submitted That Met QC Criteria

March 9, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1200.32
  • 2008-005615-18 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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