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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

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 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
Actual Study Start Date : August 14, 2009
Actual Primary Completion Date : February 9, 2012
Actual Study Completion Date : March 16, 2017


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



Primary Outcome Measures :
  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 Outcome Measures :
  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.

    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.

  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.



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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 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.

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


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

Additional 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 )
First Posted: July 30, 2009    Key Record Dates
Results First Posted: November 19, 2013
Last Update Posted: April 6, 2018
Last Verified: March 2018

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