Clinical trial NCT01125566: LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metastatic Breast Cancer Patients After One Prior Herceptin Treatment
Official title: LUX-Breast 1; An Open Label, Randomised Phase III Trial of BIBW 2992 and Vinorelbine Versus Trastuzumab and Vinorelbine in Patients With Metastatic HER2-overexpressing Breast Cancer Failing One Prior Trastuzumab Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-05-18
Enrollment: 508
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy and safety of BIBW 2992 in combination with vinorelbine i.v. chemotherapy as treatment in patients with HER2-overexpressing, metastatic breast cancer, who failed one prior trastuzumab (Herceptin®) treatment


Eligibility criteria: Inclusion criteria:

* Histologically confirmed diagnosis of HER2-overexpression breast cancer
* Stage IV metastatic disease
* Must have progressed on one prior trastuzumab treatment
* no more than one prior trastuzumab based therapy regimen (either adjuvant or first-line)
* Must have received anthracycline and/or taxane based chemotherapy for adjuvant treatment of breast cancer or first-line treatment of metastatic breast cancer
* Must have (archived) tumour tissue sample available for central re-assessment of HER2-status
* At least one measurable lesion according to RECIST 1.1.
* Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 .

Exclusion criteria:

* Prior treatment with Epidermal Growth Factor Receptor/Human Epidermal Growth Factor Receptor(EGFR/HER2)-targeted small molecules or antibodies other than trastuzumab
* Prior treatment with vinorelbine
* Known pre-existing interstitial lung disease
* Active brain metastases
* History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomisation.
* Cardiac left ventricular function with resting ejection fraction of less than 50%.
* Patients unable to comply with the protocol.
* Any contraindications for therapy with vinorelbine or trastuzumab.
* Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
* Use of any investigational drug within 4 weeks of randomisation.
* Inadequate hepatic, renal and haematologic organ function

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomisation (07Sep2010) to database lock (30Jul2018), up to 95 months.
measure: Best RECIST Assessment
timeFrame: From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months
measure: Objective Response (OR)
timeFrame: Post baseline tumour-imaging was performed at Week 8, 16, 24, 32, 40, 48, 56 and then every 12 weeks (Until final data-base lock on 30 Jul 2018; Up to 95 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers
state: Arizona
city: Fountain Valley
country: United States
facility: Robert A. Moss MD, FACP, Inc
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare
state: California
city: Los Angeles
country: United States
facility: University of California
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group, Inc
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group, Inc
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Skokie
country: United States
facility: North Shore Cancer Research Associates
state: Illinois
city: Waterloo
country: United States
facility: Cedar Valley Cancer Center
state: Iowa
city: Lake Success
country: United States
facility: Pro Health Care Associated
state: New York
city: Asheville
country: United States
facility: Hope Women's Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Cancer Center
state: Utah
city: Buenos Aires
country: Argentina
facility: Instituto Medico de Asistencia e Investigaciones S. A.
city: Capital Federal
country: Argentina
facility: Hospital Britanico
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Sanatorio de la Provodencia
city: Rosario
country: Argentina
facility: Sanatorio Parque
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital (PMBH)
state: New South Wales
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Haematology & Oncology
state: Victoria
city: Ringwood East
country: Australia
facility: Maroondah Hospital
state: Victoria
city: Perth
country: Australia
facility: Mount Medical Centre
state: Western Australia
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH - Barmherzige Schwestern
city: Wien
country: Austria
facility: Kaiser Franz Josef Spital Vienna
city: Grodno
country: Belarus
facility: Grodno Regional Clinical Hospital
city: Minsk Region
country: Belarus
facility: N. N. Alexandrov National Cancer Center of Belarus
city: Minsk
country: Belarus
facility: Public Health Inst. Minsk City Clinical Oncology Dispensary
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncology Dispensary
city: Bruxelles
country: Belgium
facility: Brussels - HOSP Jules Bordet
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Liège
country: Belgium
facility: Liège - HOSP St-Joseph
city: Cachoeiro de Itapemirim
country: Brazil
facility: Centro de Pesquisas Clínicas em Oncología
city: Curitiba
country: Brazil
facility: Hospital Santa Cruz
city: Ijui
country: Brazil
facility: Associacao Hospital de Caridade de Ijui
city: Porto Alegre
country: Brazil
facility: Associação Hospitalar Moinhos de Vento
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Centro de Novos Tratamentos CliniOnco
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional do Câncer - INCA
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC
city: Sao Paulo
country: Brazil
facility: Centro de Referência da Saude da Mulher-Hosp Perola Byington
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver
state: British Columbia
city: Moncton
country: Canada
facility: Dr. Leon Richard Oncology Centre
state: New Brunswick
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval Research Centre
city: Temuco
country: Chile
facility: Instituto Clínico Oncológico del Sur - ICOS
city: Beijing
country: China
facility: Cancer Hospital of Chinese Academy of Medical Science
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: 307 Hospital of PLA
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Changchun
country: China
facility: First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital
city: Fuzhou
country: China
facility: Fujian Provincial Tumor Hospital
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Guangzhou
country: China
facility: NanFang Hosptial
city: Haerbin
country: China
facility: The Third Affiliated Hospital of Harbin Medical University
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Jinan
country: China
facility: Qilu Hospital, Shangdong University
city: Nanjing
country: China
facility: the 81th Hospital of PLA
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Ceske Budejovice
country: Czechia
facility: Hospital Ceske Budejovice
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Prague 2
country: Czechia
facility: General Faculty Hospital, Prague
city: Praha 4
country: Czechia
facility: MEDICON a.s., Praha 4
city: Cairo
country: Egypt
facility: El Manial Specialized Hospital
city: Mansoura
country: Egypt
facility: Oncology Centre- Mansoura University
city: Amiens Cedex 1
country: France
facility: HOP Amiens-Picardie Sud
city: Angers Cedex 9
country: France
facility: CTR P Papin, Onco, Angers
city: Besançon Cedex
country: France
facility: HOP Jean Minjoz
city: Bordeaux
country: France
facility: CLI Bordeaux Nord Aquitaine
city: Clermont-Ferrand Cedex
country: France
facility: CTR J Perrin, Onco, Clermont-Ferrand
city: Le Mans
country: France
facility: HOP Victor Hugo
city: Nantes
country: France
facility: CTR Catherine de Sienne
city: Paris
country: France
facility: HOP Saint-Louis
city: Reims
country: France
facility: INS Jean Godinot, Onco, Reims
city: Rennes Cedex
country: France
facility: CTR Eugène Marquis
city: St Cloud
country: France
facility: CTR René Huguenin
city: Strasbourg Cedex
country: France
facility: CTR Paul Strauss
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, AöR
city: Bonn
country: Germany
facility: Medizinisches Zentrum Bonn
city: Bottrop
country: Germany
facility: OnkoDok GbR
city: Deggendorf
country: Germany
facility: DONAUISAR Klinikum Deggendorf-Dingolfing-Landau gKU
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Kliniken Essen - Mitte gGmbH
city: Hildesheim
country: Germany
facility: Gynäk.-onkol. Gem.praxis, Dr. Uleer, Hildesheim
city: Köln
country: Germany
facility: Universitätsklinikum Köln (AöR)
city: Köln
country: Germany
facility: St. Elisabeth-Krankenhaus
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg AöR
city: München
country: Germany
facility: Klinikum der Universität München - Campus Innenstadt
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Oldenburg
country: Germany
facility: Onkologische Praxis Oldenburg
city: Rostock
country: Germany
facility: Universitätsfrauenklinik am Klinikum Südstadt
city: Wuppertal
country: Germany
facility: Facharzt für Innere Medizin
city: Ahmedabad
country: India
facility: Gujarat Cancer and Research Institute
city: Amravati
country: India
facility: Sujan Surgical Cancer Hospital
city: Bangalore
country: India
facility: KIDWAI memoraial Institute of oncology
city: Bengaluru
country: India
facility: Sri Venkateshwara Hospital
city: Chennai
country: India
facility: Dr. Rai Memorial Cancer Centre
city: Hyderabad
country: India
facility: Bibi General Hospital and Cancer Centre
city: Kolkata
country: India
facility: Orchid Nursing Home
city: Maharagama
country: India
facility: Natinal Cancer Institute
city: Nagpur
country: India
facility: Central India Cancer Research Institute
city: Nashik
country: India
facility: Curie Manavata Cancer centre
city: Pune
country: India
facility: Jehangir Hospital Oncology Department
city: Pune
country: India
facility: K.E.M Hospital
city: Visakhapatnam
country: India
facility: King George Hospital
city: Dubliin 9
country: Ireland
facility: Beaumont Hospital
city: Dublin 4
country: Ireland
facility: St Vincent's University Hospital
city: Dublin 7
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin 8
country: Ireland
facility: St James's Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center, Jerusalem 91031
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center Tel Hashomer
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria Arcispedale Sant'Anna
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Monserrato (CA)
country: Italy
facility: P.O. Monserrato
city: Kanagawa, Isehara
country: Japan
facility: Tokai University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka Medical Center for Cancer and Cardiovascular Diseases
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Riga
country: Latvia
facility: P. Stradins Clinical Univ. Hospital, Oncology Clinic
city: Riga
country: Latvia
facility: Riga East Univ. Hospital, Oncology Centre
city: Lebanon
country: Lebanon
facility: Hammoud Hospital University Medical Centre (HHUMC)
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian Univ.of HealthSciences Kauno Klinikos
city: Vilnius
country: Lithuania
facility: National Cancer Institute, Vilnius
city: Colonia Centro
country: Mexico
facility: Hospital de Jesus
city: Dordrecht
country: Netherlands
facility: Albert SchweitzerZiekenhuis
city: Eindhoven
country: Netherlands
facility: Máxima Medisch Centrum, locatie Eindhoven
city: Geleen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Maastricht
country: Netherlands
facility: METC Academisch Ziekenhuis Maastricht/Universiteit van Maastricht
city: Zwolle
country: Netherlands
facility: Isala Zwolle
city: Cusco
country: Peru
facility: Hospital Nacional Adolfo Guevara Velasco
city: Lima
country: Peru
facility: Clinica San Judas Tadeo
city: Miraflores
country: Peru
facility: Instituto Oncologico Miraflores S.A.
city: Trujillo
country: Peru
facility: Clinica Peruano Americana de Trujillo
city: Bialystok
country: Poland
facility: Bialystock's Oncology Center
city: Bytom
country: Poland
facility: Wojewodzki Specialist Hospital No. 4, Bytom
city: Gdansk
country: Poland
facility: University Clinical Center, Gdansk
city: Lodz
country: Poland
facility: Provincial Specialist M. Kopernik Hospital
city: Lublin
country: Poland
facility: Ziemia Lubelska Oncological Center, Lublin
city: Olsztyn
country: Poland
facility: Oncology Centre of Olsztyn "KOPERNIK" Sp. z.o.o.
city: Poznan
country: Poland
facility: Wielkopolskie Oncology Centre n.a. Maria Sklodowska-Courie
city: Warsaw
country: Poland
facility: Military Medical Institute
city: Coimbra
country: Portugal
facility: Instituto Português de Oncologia de Coimbra Francisco Gentil
city: Coimbra
country: Portugal
facility: CHUC, EPE - CHC-Maternidade Bissaya Barreto
city: Lisboa
country: Portugal
facility: IPO Lisboa Francisco Gentil, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar São João,EPE
city: Porto
country: Portugal
facility: IPO Porto Francisco Gentil, EPE
city: Kazan
country: Russian Federation
facility: St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"
city: Moscow
country: Russian Federation
facility: N.A. Semashko Central Clinical Hospital, Moscow
city: Ryazan
country: Russian Federation
facility: GUZ "Regional Clinical Oncology Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: Regional Clinical Oncology Dispensary
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Center
city: Bardejov
country: Slovakia
facility: St. Jacobs Hosp.Outpat.Pneumology&Phthisiology Dept,Bardejov
city: Bratislava
country: Slovakia
facility: National Institute of Oncology, Bratislava
city: Poprad
country: Slovakia
facility: POKO Policlinic Dept. of Clinical Oncology
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
city: Johannesburg
country: South Africa
facility: WCR CMJAH Clinical Trial Site
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
city: Kraaifontein
country: South Africa
facility: GVI oncology Medi Clinic
city: Port Elizabeth
country: South Africa
facility: Langenhoven Drive Oncology Centre
city: Pretoria
country: South Africa
facility: Wilgers oncology
city: Rondebosch, Cape Town
country: South Africa
facility: Rondebosch Oncology Centre
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular - Materno Infantil
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico de Santiago
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Maharashtra
country: Sri Lanka
facility: Shatabdi Superspeciality Hospital
city: Changhua
country: Taiwan
facility: Chang-Hua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: NCKUH
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipe Veterans General Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yet-Sen Cancer Center
city: Taoyuan County
country: Taiwan
facility: Chang Gung Memorial Hospital(TaoYuan)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi, Ic Hastaliklari ABD
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Tibbi Onkoloji Bilim Dali
city: Dundee
country: United Kingdom
facility: Ninewells Hospital & Medical School
city: London
country: United Kingdom
facility: Guy's Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
city: Woolwich, London
country: United Kingdom
facility: Queen Elizabeth Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M; LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):357-366. doi: 10.1016/S1470-2045(15)00540-9. Epub 2016 Jan 26.