BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation
- Conditions
- Carcinoma, Non-Small-Cell LungAdenocarcinoma
- Interventions
- Registration Number
- NCT00949650
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 345
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIBW 2992 BIBW 2992 BIBW 2992 tablet once daily until progression Cisplatin/Pemetrexed Pemetrexed Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles Cisplatin/Pemetrexed Cisplatin Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Time 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
Name Time Method Percentage of Patients With Objective Response (OR) 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.
Percentage of Participants With Disease Control (DC) 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.
Overall Survival (OS) Time From randomisation to cut-off date (17MAR2017). OS was defined as time from randomisation to death.
Tumour Shrinkage 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.
Change From Baseline in Body Weight 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.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 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.Trough Plasma Concentrations of Afatinib at Day 22 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.
Trough Plasma Concentrations of Afatinib at Day 43 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.
Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing 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.
HRQOL: Time to Deterioration in Dyspnoea 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.
Trough Plasma Concentrations of Afatinib at Day 29 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.
HRQOL: Time to Deterioration in Pain 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.
Trial Locations
- Locations (132)
Imcaba S.R.L.
🇦🇷Capital Federal, Argentina
Lungenklinik Hemer
🇩🇪Hemer, Germany
Hospital São Lucas da Pontifícia Universidade Católica
🇧🇷Porto Alegre, Brazil
Klinikum Wels - Grieskirchen GmbH
🇦🇹Wels, Austria
Lehigh Valley Hospital / Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
IMAI Research
🇦🇷Capital Federal, Argentina
Calvary Mater Newcastle Hospital
🇦🇺Waratah, New South Wales, Australia
HOP - HIA Sainte Anne
🇫🇷Toulon, France
UZ Leuven
🇧🇪Leuven, Belgium
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Zala County Hospital, Zalaegerszeg
🇭🇺Zalaegerszeg, Hungary
Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Insituto de Oncologia do Paraná
🇧🇷Curitiba, Brazil
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
National Hospital Organization Nagoya Medical Center
🇯🇵Aichi, Nagoya, Japan
Instituto de Medicina Nuclear de Bahía Blanca
🇦🇷Bahía Blanca, Argentina
Universitätsklinikum Benjamin Franklin, Berlin
🇩🇪Berlin, Germany
Az. USL 4 di Prato
🇮🇹Prato, Italy
Clinical Trials and Research Associates Inc
🇺🇸Montebello, California, United States
Centro Oncológico de Rosario
🇦🇷Rosario, Argentina
HOP Sud-Réunion, Pneumo, Saint Pierre
🇫🇷Saint Pierre - La Réunion, France
Instituto Alexander Fleming
🇦🇷Capital Federal, Argentina
Centro de Pesquisa do Hospital Lifecenter
🇧🇷Belo Horizonte, Brazil
UNIV UZ Gent
🇧🇪Gent, Belgium
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
The Burnside War Memorial Hospital
🇦🇺Toorak Gardens, South Australia, Australia
Charles LeMoyne Hospital
🇨🇦Greenfield Park, Migration Data, Canada
UNIFESP Departamento de Medicina de Pneumologia
🇧🇷Sao Paulo, Brazil
Centro de Pesquisas Clínicas em Oncología
🇧🇷Cachoeiro de Itapemirim, Brazil
HOP d'Angers
🇫🇷Angers, France
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
Kanazawa University Hospital
🇯🇵Ishikawa, Kanazawa, Japan
Hematologiste et oncologue medical CHUM - Hopital Notre-Dame
🇨🇦Montreal, Migration Data, Canada
Brussels - UNIV UZ Brussel
🇧🇪Jette, Belgium
National Cancer Center Hospital East
🇯🇵Chiba, Kashiwa, Japan
Ospedale San Donato di Arezzo
🇮🇹Arezzo, Italy
McGill University, Department of Oncology
🇨🇦Montreal, Migration Data, Canada
HOP Nord Michallon
🇫🇷La Tronche, France
CTR René Gauducheau
🇫🇷Saint Herblain, France
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Kanagawa, Yokohama, Japan
Instituto Oncológico Limitada Viña del Mar
🇨🇱Reñaca, Chile
University Malaya Medical Centre
🇲🇾Wilayah Persekutuan, Malaysia
National Hospital Organization Kinki-Chuo Chest Medical Center
🇯🇵Sakai, Osaka, Japan
Markusovszky County Hospital, Szombathely
🇭🇺Szombathely, Hungary
Royal Surrey County Hospital
🇬🇧Guildford, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Srinagarind Hospital
🇹🇭Khonkaen, Thailand
Chungbuk National University Hospital
🇰🇷Cheongju, Korea, Republic of
National Taiwan University Hospital
🇩🇪Taipei, Germany
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
National Hospital Organization Shikoku Cancer Center
🇯🇵Ehime, Matsuyama, Japan
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Hospital Nacional Guillermo Almenara Irigoyen
🇵🇪La Victoria, Peru
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
FSBSI "N.N Blokhin Medical Research Center of Oncology"
🇷🇺Moscow, Russian Federation
Osaka City Hospital Organization Osaka City General Hospital
🇯🇵Osaka, Osaka, Japan
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
🇮🇹Roma, Italy
Chang Gung Memorial Hospital Kaohsiung
🇨🇳Kaohsiung, Taiwan
Hokkaido University Hospital
🇯🇵Hokkaido, Sapporo, Japan
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Scunthorpe General Hospital, Oncology
🇬🇧Scunthorpe, United Kingdom
Shizuoka Cancer Center
🇯🇵Shizuoka, Sunto-gun, Japan
Mount Medical Centre
🇦🇺Perth, Western Australia, Australia
Kurashiki Central Hospital
🇯🇵Okayama, Kurashiki, Japan
HOP Côte de Nacre
🇫🇷Caen Cedex 5, France
HOP Croix Rousse, Pneumo, Lyon
🇫🇷Lyon Cedex 4, France
INS Curie
🇫🇷Paris Cedex 05, France
St. Vincents Hospital (MEL)
🇦🇺Fitzroy, Victoria, Australia
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Crescent City Research Consortiom
🇺🇸Marrero, Louisiana, United States
Hospital Alemán
🇦🇷Capital Federal, Argentina
PALIAR
🇦🇷Capital Federal, Argentina
SMZ Baumgartner Hoehe Otto Wagner Spital
🇦🇹Wien, Austria
Centre Hospitalier Universitaire de Liège
🇧🇪Liège, Belgium
Instituto Clínico Oncológico del Sur - ICOS
🇨🇱Temuco, Chile
HOP, Pneumo, Villefranche sur Saône
🇫🇷Villefranche Sur Saône, France
Universitätsklinikum Münster
🇩🇪Münster, Germany
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
🇩🇪Essen, Germany
Pius-Hospital, Oldenburg
🇩🇪Oldenburg, Germany
Osp. Silvestrin
🇮🇹Sant'Andrea Delle Fratte (PG), Italy
Aichi Cancer Center Hospital
🇯🇵Aichi, Nagoya, Japan
Institute of Biomedical Research and Innovation Hospital
🇯🇵Hyogo, Kobe, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Fukuoka, Japan
Okayama University Hospital
🇯🇵Okayama, Okayama, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Niigata, Japan
Kindai University Hospital
🇯🇵Osaka, Osaka-Sayama, Japan
Republic Clinical Oncology Dispensary, Dept. Chemotherapy
🇷🇺Kazan, Russian Federation
St. Luke Medical Centre
🇵🇭Quezon, Philippines
Instituto Nacional de Enfermedades Neoplásicas
🇵🇪Surquillo, Peru
First Pavlov State Medical University Saint Petersburg
🇷🇺St. Petersburg, Russian Federation
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Medical Radiology Science Centre
🇷🇺Obninsk, Russian Federation
SPb SBIH "City Clinical Oncological Dispensary"
🇷🇺St. Petersburg, Russian Federation
FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
🇷🇺St. Petersburg, Russian Federation
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Maidstone Hospital, Kent Oncology Centre
🇬🇧Maidstone, United Kingdom
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
KH d. Elisabethinen Linz
🇦🇹Linz, Austria
ONCOLAB SRL, Craiova
🇷🇴Craiova, Romania
Brussels - UNIV St-Pierre
🇧🇪Bruxelles, Belgium
Perpetual Succour Hospital (Cebu)
🇵🇭Cebu City, Philippines
Taipe Veterans General Hospital
🇨🇳Taipei, Taiwan
Hospital Dirección de Previsión de Carabineros
🇨🇱Los Condes, Chile
Clínica Anglo Americana
🇵🇪San Isidro, Peru
Institutul Oncologic "Prof. Dr. Ion Chiricuta"
🇷🇴Cluj Napoca, Romania
Chang Gung Memorial Hospital(TaoYuan)
🇨🇳Taoyuan, Taiwan
Songklanagarind Hospital
🇹🇭Songkla, Thailand
Szent György Hospital, Szekesfehervar
🇭🇺Szekesfehervar, Hungary
St James's Hospital
🇮🇪Dublin 8, Ireland
Hospital Pulau Pinang
🇲🇾Palau Pinang, Malaysia
Pusat Perubatan University Kebangsaan Malaysia
🇲🇾Wilayah Persekutuan, Malaysia
Makati Medical Center
🇵🇭Makati City, Philippines
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
NCKUH
🇨🇳Tainan, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Maharaj Nakorn Chiang Mai Hospital
🇹🇭Chiang Mai, Thailand
City Clinical Hospital #4, Dnipropetrovsk State Medical Academy
🇺🇦Dnipropetrovsk, Ukraine
Kharkiv Regional Clinical Oncology Center
🇺🇦Kharkiv, Ukraine
Lviv State Oncological Regional Treatment & Diagnostic CTR
🇺🇦Lviv, Ukraine
Donetsk Regional Antitumor Centre
🇺🇦Donetsk, Ukraine
Innovative Medical Research of South Florida
🇺🇸Miami, Florida, United States
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Interlakes Foundation, Incorporated
🇺🇸Rochester, New York, United States
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Cross Cancer Institute (University of Alberta)
🇨🇦Edmonton, Alberta, Canada
South Texas Institute of Cancer, Northwest Cancer Center
🇺🇸Corpus Christi, Texas, United States
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Hospital Militar Central
🇦🇷Capital Federal, Argentina
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong