LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metastatic Breast Cancer Patients After One Prior Herceptin Treatment

Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01125566
• Other study ID #: 1200.75
• Secondary ID: 2009-015476-98
• Status: Completed
• Phase: Phase 3
• Start date: June 22, 2010
• Est. completion date: July 6, 2018

Study information

• Verified date: July 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 508
• Est. completion date: July 6, 2018
• Est. primary completion date: June 8, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• BIBW 2992
patients receive BIBW 2992 tablets once daily and can reduce dose for adverse event management
• trastuzumab
patients receive trastuzumab 2mg/kg intravenously every week
• vinorelbine
patients receive vinorelbine 25mg/m² intravenously every week
• vinorelbine
patients receive vinorelbine 25mg/m² intravenously every week

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  Egypt,  France,  Germany,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lebanon,  Lithuania,  Mexico,  Netherlands,  Peru,  Poland,  Portugal,  Russian Federation,  Singapore,  Slovakia,  Slovenia,  South Africa,  Spain,  Sri Lanka,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by investigator according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment.; Only data collected until the cut-off date for RECIST 1.1 based endpoints (08Jun2013) were considered.; Progression of disease was determined if at least 1 of the following criteria applied: At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm; Appearance of 1 or more new lesions; Unequivocal progression of existing non-target lesions	From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months
Secondary	Overall Survival (OS)	OS is defined as time from randomisation to death irrespective of the cause of the death.; For patients who had not died up to the cut-off date (03Sep2013), the date they were last known to be alive was derived from the patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date.	From randomisation (07Sep2010) to database lock (30Jul2018), up to 95 months.
Secondary	Best RECIST Assessment	Best RECIST assessment is defined as CR, PR, stable disease (SD), progressive disease (PD) or not evaluable by investigator (RECIST version 1.1).; CR for target lesions (TL): Disappearance of all target lesions.; CR for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis).; PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters.; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest SoD while on study.; PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions.	From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months
Secondary	Objective Response (OR)	OR is defined as complete response (CR) and partial response (PR). Assessed by investigator according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. Complete Response (CR) for target lesions (TL): Disappearance of all target lesions.; Complete Response (CR) for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis); Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.; Other factors which add to the overall response of an imaging timepoint as PR are as below:-; CR in TL, but non-CR/Non-PD in NTL leads to PR; CR in TL, but not evaluated NTL leads to PR; PR in TL, but non-PD NTL or not all evaluated NTL leads to PR	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)

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