Clinical trial NCT00949650: BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-07-30
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Progression-Free Survival (PFS) Time
timeFrame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Secondary outcomes:
measure: Percentage of Patients With Objective Response (OR)
timeFrame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
measure: Percentage of Participants With Disease Control (DC)
timeFrame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
measure: Overall Survival (OS) Time
timeFrame: From randomisation to cut-off date (17MAR2017).
measure: Tumour Shrinkage
timeFrame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
measure: Change From Baseline in Body Weight
timeFrame: Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
measure: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
timeFrame: Throughout the trial until progression (every 3 weeks), up to 28 months.
measure: Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing
timeFrame: Throughout the trial until progression (every 3 weeks).
measure: HRQOL: Time to Deterioration in Dyspnoea
timeFrame: Throughout the trial until progression (every 3 weeks).
measure: HRQOL: Time to Deterioration in Pain
timeFrame: Throughout the trial until progression (every 3 weeks).
measure: Trough Plasma Concentrations of Afatinib at Day 22
timeFrame: Day 22.
measure: Trough Plasma Concentrations of Afatinib at Day 29
timeFrame: Day 29.
measure: Trough Plasma Concentrations of Afatinib at Day 43
timeFrame: Day 43.
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Montebello
country: United States
facility: Clinical Trials and Research Associates Inc
state: California
city: Miami
country: United States
facility: Innovative Medical Research of South Florida
state: Florida
city: Marrero
country: United States
facility: Crescent City Research Consortiom
state: Louisiana
city: Rochester
country: United States
facility: Interlakes Foundation, Incorporated
state: New York
city: Allentown
country: United States
facility: Lehigh Valley Hospital / Lehigh Valley Health Network
state: Pennsylvania
city: Corpus Christi
country: United States
facility: South Texas Institute of Cancer, Northwest Cancer Center
state: Texas
city: Bahía Blanca
country: Argentina
facility: Instituto de Medicina Nuclear de Bahía Blanca
city: Capital Federal
country: Argentina
facility: Hospital Alemán
city: Capital Federal
country: Argentina
facility: Imcaba S.R.L.
city: Capital Federal
country: Argentina
facility: IMAI Research
city: Capital Federal
country: Argentina
facility: Instituto Alexander Fleming
city: Capital Federal
country: Argentina
facility: Hospital Militar Central
city: Capital Federal
country: Argentina
facility: PALIAR
city: Rosario
country: Argentina
facility: Centro Oncológico de Rosario
city: Camperdown
country: Australia
facility: Lifehouse
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Toorak Gardens
country: Australia
facility: The Burnside War Memorial Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincents Hospital (MEL)
state: Victoria
city: Perth
country: Australia
facility: Mount Medical Centre
state: Western Australia
city: Linz
country: Austria
facility: KH d. Elisabethinen Linz
city: Wels
country: Austria
facility: Klinikum Wels - Grieskirchen GmbH
city: Wien
country: Austria
facility: SMZ Baumgartner Hoehe Otto Wagner Spital
city: Bruxelles
country: Belgium
facility: Brussels - UNIV St-Pierre
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: Jette
country: Belgium
facility: Brussels - UNIV UZ Brussel
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Belo Horizonte
country: Brazil
facility: Centro de Pesquisa do Hospital Lifecenter
city: Cachoeiro de Itapemirim
country: Brazil
facility: Centro de Pesquisas Clínicas em Oncología
city: Curitiba
country: Brazil
facility: Insituto de Oncologia do Paraná
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da Pontifícia Universidade Católica
city: Sao Paulo
country: Brazil
facility: UNIFESP Departamento de Medicina de Pneumologia
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute (University of Alberta)
state: Alberta
city: Greenfield Park
country: Canada
facility: Charles LeMoyne Hospital
state: Migration Data
city: Montreal
country: Canada
facility: Hematologiste et oncologue medical CHUM - Hopital Notre-Dame
state: Migration Data
city: Montreal
country: Canada
facility: McGill University, Department of Oncology
state: Migration Data
city: Los Condes
country: Chile
facility: Hospital Dirección de Previsión de Carabineros
city: Reñaca
country: Chile
facility: Instituto Oncológico Limitada Viña del Mar
city: Temuco
country: Chile
facility: Instituto Clínico Oncológico del Sur - ICOS
city: Angers
country: France
facility: HOP d'Angers
city: Caen Cedex 5
country: France
facility: HOP Côte de Nacre
city: La Tronche
country: France
facility: HOP Nord Michallon
city: Lyon Cedex 4
country: France
facility: HOP Croix Rousse, Pneumo, Lyon
city: Paris Cedex 05
country: France
facility: INS Curie
city: Saint Herblain
country: France
facility: CTR René Gauducheau
city: Saint Pierre - La Réunion
country: France
facility: HOP Sud-Réunion, Pneumo, Saint Pierre
city: Toulon
country: France
facility: HOP - HIA Sainte Anne
city: Villefranche Sur Saône
country: France
facility: HOP, Pneumo, Villefranche sur Saône
city: Berlin
country: Germany
facility: Universitätsklinikum Benjamin Franklin, Berlin
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Oldenburg
country: Germany
facility: Pius-Hospital, Oldenburg
city: Taipei
country: Germany
facility: National Taiwan University Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Szekesfehervar
country: Hungary
facility: Szent György Hospital, Szekesfehervar
city: Szombathely
country: Hungary
facility: Markusovszky County Hospital, Szombathely
city: Zalaegerszeg
country: Hungary
facility: Zala County Hospital, Zalaegerszeg
city: Dublin 8
country: Ireland
facility: St James's Hospital
city: Arezzo
country: Italy
facility: Ospedale San Donato di Arezzo
city: Prato
country: Italy
facility: Az. USL 4 di Prato
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
city: Sant'Andrea Delle Fratte (PG)
country: Italy
facility: Osp. Silvestrin
city: Aichi, Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Aichi, Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Chiba, Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Ehime, Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Fukuoka, Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hokkaido, Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Hyogo, Kobe
country: Japan
facility: Institute of Biomedical Research and Innovation Hospital
city: Ishikawa, Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
city: Niigata, Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Okayama, Kurashiki
country: Japan
facility: Kurashiki Central Hospital
city: Okayama, Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka, Osaka-Sayama
country: Japan
facility: Kindai University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka City Hospital Organization Osaka City General Hospital
city: Sakai, Osaka
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Shizuoka, Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Palau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Wilayah Persekutuan
country: Malaysia
facility: Pusat Perubatan University Kebangsaan Malaysia
city: Wilayah Persekutuan
country: Malaysia
facility: University Malaya Medical Centre
city: La Victoria
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen
city: San Isidro
country: Peru
facility: Clínica Anglo Americana
city: Surquillo
country: Peru
facility: Instituto Nacional de Enfermedades Neoplásicas
city: Cebu City
country: Philippines
facility: Perpetual Succour Hospital (Cebu)
city: Makati City
country: Philippines
facility: Makati Medical Center
city: Quezon
country: Philippines
facility: St. Luke Medical Centre
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic "Prof. Dr. Ion Chiricuta"
city: Craiova
country: Romania
facility: ONCOLAB SRL, Craiova
city: Kazan
country: Russian Federation
facility: Republic Clinical Oncology Dispensary, Dept. Chemotherapy
city: Moscow
country: Russian Federation
facility: FSBSI "N.N Blokhin Medical Research Center of Oncology"
city: Obninsk
country: Russian Federation
facility: Medical Radiology Science Centre
city: St. Petersburg
country: Russian Federation
facility: First Pavlov State Medical University Saint Petersburg
city: St. Petersburg
country: Russian Federation
facility: SPb SBIH "City Clinical Oncological Dispensary"
city: St. Petersburg
country: Russian Federation
facility: FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: NCKUH
city: Taipei
country: Taiwan
facility: Taipe Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital(TaoYuan)
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Khonkaen
country: Thailand
facility: Srinagarind Hospital
city: Songkla
country: Thailand
facility: Songklanagarind Hospital
city: Dnipropetrovsk
country: Ukraine
facility: City Clinical Hospital #4, Dnipropetrovsk State Medical Academy
city: Donetsk
country: Ukraine
facility: Donetsk Regional Antitumor Centre
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center
city: Lviv
country: Ukraine
facility: Lviv State Oncological Regional Treatment & Diagnostic CTR
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital, Kent Oncology Centre
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital, Oncology
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
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