A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer Who Have Received Prior Anti-HER2 And Chemotherapy-based Treatment

Breast Cancer Clinical Trial

Official title:

A Two-Cohort, Open-Label, Multicenter Study of Trastuzumab Emtansine (T-DM1) in HER2-Positive Locally Advanced or Metastatic Breast Cancer Patients Who Have Received Prior Anti-HER2 and Chemotherapy-Based Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01702571
• Other study ID #: MO28231
• Secondary ID: 2012-001628-37
• Status: Completed
• Phase: Phase 3
• Start date: November 27, 2012
• Est. completion date: July 31, 2020

Study information

• Verified date: March 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This two-cohort, open-label, multicenter study will assess the safety, efficacy and tolerability of trastuzumab emtansine in participants with HER2-positive locally advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior anti-HER2 and chemotherapy-based treatment. Participants in Cohort 1 will be drawn from the general participant population; Cohort 2 will include only Asian participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2185
• Est. completion date: July 31, 2020
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HER2-positive disease determined locally

• Histologically or cytologically confirmed invasive breast cancer

• Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced or metastatic setting must include both chemotherapy, alone or in combination with another agent, and an anti-HER2 agent, alone or in combination with another agent

• Documented progression of incurable, unresectable, LABC, or mBC, defined by the investigator: progression must occur during or after most recent treatment for LABC/mBC or within 6 months of completing adjuvant therapy

• Measurable and/or non-measurable disease

• Left ventricular ejection fraction (LVEF) >/=50% by either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2

• Adequate organ function

• Use of highly effective contraception as defined by the protocol

Exclusion Criteria:

• History of treatment with trastuzumab emtansine

• Prior enrollment into a clinical study containing trastuzumab emtansine regardless of having received trastuzumab emtansine or not

• Peripheral neuropathy of Grade >/= 3 per National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v 4.0

• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer

• History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to first study treatment except hormone therapy, which can be given up to 7 days prior to first study treatment; recovery of treatment-related toxicity consistent with other eligibility criteria

• History of exposure to cumulative doses of anthracyclines

• History of radiation therapy within 14 days of first study treatment. The participant must have recovered from any resulting acute toxicity (to Grade </=1) prior to first study treatment.

• Metastatic central nervous system (CNS) disease only

• Brain metastases which are symptomatic

• History of a decrease in LVEF to less than (<) 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment

• History of symptomatic CHF (New York Heart Association [NYHA] Classes II-IV) or serious cardiac arrhythmia requiring treatment

• History of myocardial infarction or unstable angina within 6 months of first study treatment

• Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy

• Current severe, uncontrolled systemic disease (clinically significant cardiovascular, pulmonary, or metabolic disease)

• Pregnancy or lactation

• Currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus

• History of intolerance (such as Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Trastuzumab Emtansine
Participants will receive trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenously on Day 1 of a 3-week cycle every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.

Locations

Country	Name	City	State
Argentina	CEMIC	Buenos Aires
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Argentina	Hospital Privado De Comunidad; General Practice	Mar Del Plata
Australia	Ashford Cancer Center Research	Kurralta Park	South Australia
Australia	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Mater Hospital; Patricia Ritchie Centre for Cancer Care and Research	North Sydney	New South Wales
Australia	Haematology & Oncology Clinics of Australia Research Centre	South Brisbane	Queensland
Australia	Sunshine Hospital; Oncology Research	St Albans	Victoria
Australia	Calvary Mater Newcastle; Medical Oncology	Waratah	New South Wales
Australia	Westmead Hospital; Medical Oncology and Pallative Care	Westmead	New South Wales
Austria	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg
Austria	Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie	Wien
Austria	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie	Wien
Belgium	Institut Jules Bordet	Anderlecht
Belgium	UZ Brussel	Brussel
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	CHU Sart-Tilman	Liège
Belgium	Clinique Ste-Elisabeth	Namur
Belgium	Sint Augustinus Wilrijk, Apotheek	Wilrijk
Brazil	Centro de Pesquisas Oncologicas - CEPON	Florianopolis	SC
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	*X*Instituto Nacional do Cancer - INCA	Rio de Janeiro	RJ
Brazil	Hospital Sao Jose	Sao Paulo	SP
Brazil	Hospital Sirio Libanes; Centro de Oncologia	Sao Paulo	SP
Bulgaria	MHAT Serdika; Department of medical oncology	Sofia
Bulgaria	SHATO - Sofia	Sofia
Bulgaria	SHATOD - Sofia	Sofia
Bulgaria	District Oncology Dispensary Wit Stationary	Varna
Canada	Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials	Barrie	Ontario
Canada	London Regional Cancer Centre	London	Ontario
Canada	Hopital Maisonneuve- Rosemont; Oncology	Montreal	Quebec
Canada	Mcgill University - Royal Victoria Hospital; Oncology	Montreal	Quebec
Canada	Southlake Regional Health Center; Community Care Clinic / Oncology	Newmarket	Ontario
Canada	Dr. H. Bliss Murphy Cancer Centre; Oncology	St. John's	Newfoundland and Labrador
Canada	BC Cancer - Surrey	Surrey	British Columbia
Canada	St. Michael'S Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre	Vancouver	British Columbia
China	Beijing Cancer Hospital	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences.	Beijing
China	Chinese PLA General Hospital	Beijing
China	Sun Yat-sen Memorial Hospital	Guangzhou
China	Sun Yet-sen University Cancer Center	Guangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Jiangsu Cancer Hospital	Nanjing City
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Tianjin Cancer Hospital	Tianjin
China	Zhejiang Cancer Hospital	Zhejiang
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Denmark	Aalborg Universitetshospital, Klinik Kirurgi-Kræft, Onkologisk afd.	Aalborg
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
Denmark	Nordsjællands Hospital, Hillerød, Onkologisk Afdeling	Hillerod
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Denmark	Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium	Roskilde
Denmark	Vejle Sygehus; Onkologisk Afdeling	Vejle
Dominican Republic	Hospital Metropolitano de Santiago	Santiago
Ecuador	Clinica Alcivar, torre 1;Private office	Guayaquil
Ecuador	Hospital Solca Portoviejo; Oncologia	Portoviejo
Estonia	North Estonia Medical Centre Foundation; Oncology Center	Tallinn
Finland	Helsingin yliopistollinen keskussairaala	Helsinki
Finland	KYS Sadesairaala; Syopatautien poliklinikka	Kuopio
Finland	Tampere University Hospital; Dept of Oncology	Tampere
Finland	Turku Uni Central Hospital; Oncology Clinics	Turku
France	Clinique De L Europe; Radiotherapie Chimiotherapie	Amiens
France	ICO Paul Papin; Oncologie Medicale.	Angers
France	Institut Sainte Catherine	Avignon
France	Hopital Jean Minjoz - CHU de Besançon	Besançon
France	Clinique Tivoli; Chimiotherapie Radiotherapie	Bordeaux
France	Institut Bergonie; Oncologie	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie	Bordeaux
France	Cli De La Porte De Saint Cloud; Hop De Jour De Chimiotherapie	Boulogne-billancourt
France	Hopital Morvan; Oncologie - Radiotherapie	Brest
France	Centre Francois Baclesse; Radiotherapie	Caen
France	Centre Jean Perrin; Oncologie	Clermont Ferrand
France	Centre Georges Francois Leclerc; Oncologie 3	Dijon
France	Chu Grenoble - Hopital Albert Michallon; Departement de Cancero-Hematologie	Grenoble
France	Centre Hartmann	Levallois Perret
France	Centre Oscar Lambret; Senologie	Lille
France	Clinique Chenieux; Oncology	Limoges
France	Ch Bretagne Sud Site Scorff; Oncologie Medicale	Lorient
France	Centre Leon Berard	Lyon
France	Institut Paoli Calmettes; Oncologie Medicale	Marseille
France	Hopital Layne; Medecine Ambulatoire	Mont-de-marsan
France	Centre Val Aurelle Paul Lamarque; Recherche Clinique	Montpellier
France	Centre Antoine Lacassagne; Hopital De Jour A2	Nice
France	HOPITAL TENON; Cancerologie Medicale	Paris
France	Institut Curie; Oncologie Medicale	Paris
France	Polyclinique Francheville; Med Chimiotherapie Radiotherapie	Perigueux
France	Centre Catalan D' Oncologie	Perpignan
France	Clinique Armoricaine Radiologie; Hopital de Jour	Plerin
France	Pole Regional De Cancerologie	Poitiers
France	Polyclinique De Courlancy; Centre Radiotherapie Oncologie	Reims
France	Institut Jean Godinot; Oncologie Medicale	Reims CEDEX
France	Centre Eugene Marquis; Unite Huguenin	Rennes
France	Centre Henri Becquerel; Oncologie Medicale	Rouen
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Centre Rene Huguenin; CONSULT SPECIALISEES	St Cloud
France	Centre Paul Strauss; Oncologie Medicale	Strasbourg
France	Clinique Pasteur; Oncologie Medicale	Toulouse
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
France	Centre Henry S Kaplan - CHU Bretonneau ; service oncologie	Tours
France	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre-les-nancy
France	Institut Gustave Roussy; Pathologie Mammaire	Villejuif
Germany	Hämatologisch-onkologische Praxis Dr. med. - Heinrich, - Bangerter	Augsburg
Germany	Praxis Dres. Schilling & Till	Berlin
Germany	Schwerpunktpraxis Onkologie/Hämatologie Dr. Dirk Pott, Dr. Christian Tirier und Carla Verena u.w.	Bottrop
Germany	Onkozentrum Dres. Göhler	Dresden
Germany	Dres. Joerg Weniger, Annette Bittrich und Berit Schuetze	Erfurt
Germany	Universitätsklinikum Erlangen; Frauenklinik	Erlangen
Germany	HOPA MVZ GmbH	Hamburg
Germany	OncoResearch Lerchenfeld GmbH	Hamburg
Germany	Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie	Hannover
Germany	Institut für Versorgungsforschung in der Onkologie GbR Koblenz	Koblenz
Germany	Klinikum Leverkusen; Med. Klinik III / Onkologie	Leverkusen
Germany	Klinikum der Universität München; Campus Großhadern; Klinik und Poliklinik für Frauenheilkunde	Muenchen
Germany	Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe	Münster
Germany	Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe	Offenbach
Germany	Praxis für Hämatologie und Onkologie	Porta Westfalica
Germany	Universitaetsfrauenklinik; Und Poliklinik Am Klinikum	Rostock
Germany	Universitätsklinik Tübingen; Frauenklinik	Tübingen
Germany	HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie	Wiesbaden
Germany	Hämatologisch-Onkologische Schwerpunktpraxis Dres. Schlag & Schöttker	Würzburg
Greece	University General Hospital of Heraklion	Crete
Greece	Uni Hospital of Ioannina; Oncology Dept.	Ioannina
Greece	University Hospital of Patras Medical Oncology	Patras
Greece	Papageorgiou General Hospital; Medical Oncology	Thessaloniki
Guatemala	Centro Oncológico Sixtino / Centro Oncológico SA	Guatemala
Hong Kong	Princess Margaret Hospital; Oncology	Hong Kong
Hong Kong	Prince of Wales Hosp; Dept. Of Clinical Onc	Shatin
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely	Budapest
Hungary	Ogyi, Orszagos Gyogyszereszeti Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest
Hungary	Szent Imre Hospital; Dept. of Oncology	Budapest
Hungary	Kaposi Mor County Hospital; Dept. of Oncology	Kaposvar
Iceland	Landspitali University Hospital, Department of Medical Oncology	Reykjavik
Indonesia	Cipto Mangunkusumo General Hospital; Hematology & Oncology	Jakarta
Indonesia	Dharmais National Cancer Center	Jakarta
Indonesia	MRCCC Siloam Semanggi Hospital	Jakarta
Ireland	Cork Uni Hospital; Oncology Dept	Cork
Ireland	Mater Misericordiae Uni Hospital; Oncology	Dublin
Ireland	St Vincent'S Uni Hospital; Medical Oncology	Dublin
Ireland	University Hospital Limerick - Oncology	Limerick
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino	Campania
Italy	RCCS - Centro di Riferimento; Oncologia Medica B	Aviano (PN)	Friuli-Venezia Giulia
Italy	Ospedale Bellaria; U.O. Oncologia Medica	Bologna	Emilia-Romagna
Italy	Ospedale Antonio Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Ospedale Civile; Oncologia Medica	Camposampiero	Veneto
Italy	Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico	Candiolo	Piemonte
Italy	Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica	Catania	Sicilia
Italy	ASST DI CREMONA; Unità di Patologia Mammaria Senologia e Breast Unit	Cremona	Lombardia
Italy	A.O.U Careggi	Florence	Toscana
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	Ospedale Vito Fazzi; Div. Oncoematologia	Lecce	Puglia
Italy	ASST DI LECCO; Oncologia Medica	Lecco	Lombardia
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Ospedale San Raffaele; Medical Oncology	Milano	Lombardia
Italy	A.O.U. Policlinico di Modena	Modena	Emilia-Romagna
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	Università degli Studi Federico II; Clinica di Oncologia Medica	Napoli	Campania
Italy	Ospedale Maggiore Della Carita; Oncologia Medica	Novara	Piemonte
Italy	Ospedale Busonera; Oncologia Medica	Padova	Veneto
Italy	Fondazione Salvatore Maugeri; Divisione Di Oncologia Medica	Pavia	Lombardia
Italy	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Perugia	Umbria
Italy	Az. Osp. Ospedale Civile; U.O. Di Oncologia Medica Ed Ematologia	Piacenza	Emilia-Romagna
Italy	Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia	Pontedera	Toscana
Italy	Ospedale Misericordia E Dolce; Oncologia Medica	Prato	Toscana
Italy	Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche	Roma	Lazio
Italy	Casa di Cura Multimedica S.p.A.; Dipartimento Oncologico	Sesto San Giovanni (MI)	Lombardia
Italy	Ospedale S.S. Trinità Nuovo; Divisione Oncologia	Sora	Lazio
Italy	A.O. Città della Salute e della Scienza - Presidio Molinette; divisione oncologia medica	Torino	Piemonte
Italy	Divisione Onc Med dell'Azienda	Udine	Friuli-Venezia Giulia
Italy	A.O.U.I. VERONA-OSPEDALE BORGO TRENTO; ONCOLODIA MEDICA-d.O.	Verona	Veneto
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	Gachon Medical School Gil Medical Center; Medical Oncology	Incheon
Korea, Republic of	Korea University Anam Hospital; Oncology Haemotology	Seoul
Korea, Republic of	Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology	Seoul
Korea, Republic of	Yonsei University Severance Hospital; Medical Oncology	Seoul
Luxembourg	CHL Hopital Municipal; Oncology	Luxembourg
Mexico	Medica Sur Centro Oncologico Integral	D.f.
Mexico	Hospital Hmg Coyoacan	DF
Mexico	CENTRO MÉDICO NACIONAL SIGLO XXI; Hospital de Especialidades Oncología	Mexico City
Mexico	Hospital General de México	Mexico City	Mexico CITY (federal District)
Mexico	Inst. Nacional de Cancerologia; Investigacion Clinica	Mexico City
Mexico	Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán	Mexico City
Netherlands	Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde	Amsterdam
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	MC Haaglanden; Oncologie	Den Haag
Netherlands	Deventer Ziekenhuis; Interne Geneeskunde	Deventer
Netherlands	Ziekenhuisgroep Twente, Hengelo	Hengelo
Netherlands	Spaarne Ziekenhuis; Inwendige Geneeskunde	Hoofddorp
Netherlands	Medisch Centrum Leeuwarden; Interne	Leeuwarden
Netherlands	Orbis Medisch Centrum; Inwendige Geneeskunde	Sittard-Geleen
Netherlands	Twee Steden Ziekenhuis - Locatie Tilburg; Interne Geneesekunde	Tilburg
Norway	Oslo Universitetssykehus HF; Ullevål sykehus	Oslo
Panama	Centro Hemato Oncologico Panama	Panama
Panama	Centro Oncologico America	Panama
Peru	Clinica de Especialidades Medicas	Lima
Peru	Instituto;Oncologico Miraflores	Lima
Poland	Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej	Bialystok
Poland	Szpital Specjalistyczny POO im. ks. B.Markiewicza; Dzienny Oddz Chemioter i Hematologii Onkol	Brzozów
Poland	Swietokrzyskie Centrum Onkologii; Dzial Chemioterapii	Kielce
Poland	Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Kliniki Onkologii	Kraków
Poland	Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii	Otwock
Poland	Wojewódzki Szpital Specjalistyczny Nr 3	Rybnik
Portugal	Hospital da Luz; Departamento de Oncologia Medica	Lisboa
Portugal	IPO de Lisboa; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Slovakia	Narodny Onkologicky Ustav; Oddelenie klinickej onkologie A	Bratislava
Slovakia	Fakultna nemocnica Trencín; Onkologicke odd.	Trencin
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Spain	Hospital General Univ. de Alicante; Servicio de Oncologia	Alicante
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Hospital Quiron Barcelona; Servicio de Oncologia	Barcelona
Spain	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital San Pedro De Alcantara; Servicio de Oncologia	Caceres
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital General Universitario de Elche; Servicio de Oncologia	Elche	Alicante
Spain	Hospital General de Elda; Servicio de Oncologia	Elda	Alicante
Spain	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia	Girona
Spain	Hospital Universitario San Cecilio; Servicio de Oncologia	Granada
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Hospital de Jerez de la Frontera; Servicio de Oncologia	Jerez de La Frontera	Cadiz
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	La Coruña
Spain	Hospital de Gran Canaria Dr. Negrin; Servicio de Oncologia	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Severo Ochoa; Servicio de Oncologia	Leganes	Madrid
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Univ. Central de Asturias; Servicio de Oncologia	Oviedo	Asturias
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares
Spain	Complejo Hospitalario de Pontevedra; Servicio de Oncologia	Pontevedra
Spain	Hospital Quiron de Madrid; Servicio de Oncologia	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitari Sant Joan de Reus; Servicio de Oncologia	Reus	Tarragona
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital de Donostia; Servicio de Oncologia Medica	San Sebastian	Guipuzcoa
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Spain	Hospital General Universitario de Valencia; Servicio de oncologia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Spain	Hospital Xeral Cíes; Servicio de Oncologia	Vigo	Pontevedra
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
Sweden	Karolinska Hospital; Oncology - Radiumhemmet	Stockholm
Sweden	Norrlands universitetssjukhus; Onkologkliniken	Umeå
Taiwan	Chi-Mei Medical Centre; Hematology & Oncology	Tainan
Taiwan	National Cheng Kung Uni Hospital; Surgery	Tainan
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Thailand	Department of Surgery, King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Pramongkutklao Hospital; Medicine - Medical Oncology Unit	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial	Chiang Mai
Turkey	Gazi Uni Medical Faculty Hospital; Oncology Dept	Ankara
Turkey	Gaziantep University Medical Faculty, Medical Oncology Department	Gaziantep
Turkey	Bezmialem Vakif Univ Medical; Bezmialem Vakif Univ T	Istanbul
Turkey	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul
Turkey	Istanbul Uni of Medicine Faculty; Oncology Dept	Istanbul
Turkey	Kartal Dr Lutfi Kirdar Sehir Hastanesi; Medical Oncology Department	Istanbul
Turkey	Marmara Uni Faculty of Medicine; Medical Oncology	Istanbul
Turkey	Dokuz Eylul Uni ; Medical Oncology	Izmir
Turkey	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir
Turkey	Kocaeli University Faculty of Medicine; Medical oncology	Izmit
United Arab Emirates	Tawam Hospital	Al Ain
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	University Hospital Birmingham Queen Elizabeth Hospital	Birmingham
United Kingdom	Kent & Canterbury Hospital	Canterbury
United Kingdom	University Hospital coventry; Oncology Department	Coventry
United Kingdom	Eastborne District General Hospital	Eastbourne
United Kingdom	Western General Hospital; Clinical Oncology	Edinburgh
United Kingdom	St Margaret'S Hospital; Breast Unit	Epping
United Kingdom	Royal Devon & Exeter Hospital; Oncology Centre	Exeter
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Diana Princess of Wales Hosp.	Grimsby
United Kingdom	Huddersfield Royal Infirmary	Huddersfield
United Kingdom	Castle Hill Hospital; The Queen's Centre for Oncology & Haematology	Hull
United Kingdom	Ipswich Hospital; Oncology Pharmacy	Ipswich
United Kingdom	Royal Lancaster Infirmary, Morecambe Bay Hospitals Nhs Trust	Lancaster
United Kingdom	Guys & St Thomas Hospital; Department of Oncology	London
United Kingdom	Royal Free Hospital; Dept of Oncology	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	St George'S Hospital; Oncology Research Office /Oncology Opd	London
United Kingdom	Maidstone & Tonbridge Wells Hospital; Kent Oncology Center	Maidstone
United Kingdom	Christie Hospital; Breast Cancer Research Office	Manchester
United Kingdom	Mount Vernon Hospital	Middlesex
United Kingdom	Plymouth Oncology Centre; Clinical Trials Unit	Plymouth
United Kingdom	Queen Alexandra Hospital, Portsmouth	Portsmouth
United Kingdom	Queen's Hospital; Oncology	Romford
United Kingdom	Weston Park Hospital; Cancer Clinical Trials Centre	Sheffield
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury
United Kingdom	Singleton Hospital; Pharmacy	Swansea
United Kingdom	Yeovil District Hospital; Macmillan Cancer Unit	Yeovil
United Kingdom	York District Hospital	York
Venezuela	Unidad de Mastologia y Atencion a la Mujer	Barcelona
Venezuela	Instituto de Oncologia y Hematologia UCV	Caracas
Venezuela	Instituto Oncológico Luis Razetti	Caracas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Croatia,  Denmark,  Dominican Republic,  Ecuador,  Estonia,  Finland,  France,  Germany,  Greece,  Guatemala,  Hong Kong,  Hungary,  Iceland,  Indonesia,  Ireland,  Italy,  Korea, Republic of,  Luxembourg,  Mexico,  Netherlands,  Norway,  Panama,  Peru,  Poland,  Portugal,  Slovakia,  Slovenia,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Arab Emirates,  United Kingdom,  Venezuela, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events of Primary Interest (AEPIs)	The AEPIs in this study were defined as the following: adverse events (AEs) Grade >/= 3, specifically, hepatic events, allergic reactions, thrombocytopenia and hemorrhage events, all Grade >/= 3 AEs related to trastuzumab emtansine and pneumonitis events of all grades.	Baseline up to approximately 7 years
Secondary	Percentage of Participants With Specific AEPIs	The AEPIs in this study were defined as the following: adverse events (AEs) Grade >/= 3, specifically, hepatic events, allergic reactions, thrombocytopenia and hemorrhage events, all Grade >/= 3 AEs related to trastuzumab emtansine and pneumonitis events of all grades.	Baseline up to approximately 7 years
Secondary	Percentage of Participants With Adverse Events of Special Interest (AESIs)	AESIs included: 1) Potential drug-induced liver injury, which included any potential case of drug-induced liver injury as, assessed by laboratory criteria for Hy's law (AST and/or ALT elevations that were >3 × ULN, Concurrent elevation of total bilirubin >2 × ULN (or clinical jaundice if total bilirubin measures were not available), except in participants with documented Gilbert's syndrome. Those with Gilbert's syndrome, elevation of direct bilirubin >2 × ULN was used instead. 2) Suspected transmission of an infectious agent by study drug was defined as any organism, virus, or infectious particle (e.g., prion protein transmitting transmissible spongiform encephalopathy), pathogenic or non-pathogenic. A transmission of an infectious agent suspected from clinical symptoms or laboratory findings indicating an infection in a participant exposed to a medicinal product.	Baseline up to approximately 7 years
Secondary	Progression-Free Survival According to Response Evaluation for Solid Tumors (RECIST) Version (v) 1.1 As Per Investigator Assessment	Progression free survival is defined as the time (in months) between the date of first dose and the date of disease progression or death from any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).	Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years)
Secondary	Overall Survival	Overall survival is defined as time to death, which is the time from the date of dosing until the date of death, regardless of the cause of death.	Baseline until death (up to approximately 7 years)
Secondary	Percentage of Participants With Best Overall Response (Complete Response [CR] or Partial Response [PR]) According to RECIST v 1.1 As Per Investigator Assessment	Best Overall Response reported here is the Best confirmed Overall Response. To be assigned a status of PR or CR, i.e., to be a responder, changes in tumor measurements had to be confirmed by repeat assessments that had to be performed no less than 4 weeks after the criteria for response were first met, i.e., participants needed to have two consecutive assessments of PR or CR. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.	Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years)
Secondary	Percentage of Participants With Clinical Benefit (CR or PR or Stable Disease [SD]) According to RECIST v 1.1	Clinical Benefit was defined as CR plus PR plus SD. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD: neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.	Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years)
Secondary	Duration of Response (DOR) According to RECIST v 1.1	DOR is defined as the period from the date of initial confirmed PR or CR (whichever occurs first) until the date of PD or death from any cause. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 millimeters (mm).	Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years)
Secondary	Time to Response According to RECIST v 1.1	Time to Response is defined as the time from first dose to first documentation of confirmed PR or CR (whichever occurs first). CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.	Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 7 years)
Secondary	Number of Hospital Visits	The number of hospital visits were recorded to evaluate the resoruce expenditures while participants were on study treatment.	Baseline up to approximately 7 years
Secondary	Type of Hospital Visits	The type of hospital visits (intensive care unit (ICU) versus other) were recorded to evaluate the resoruce expenditures while participants were on study treatment. The number of participants with at least one ICU visit are based on the number of participants with at least one hospital visit, in each group.	Baseline up to approximately 7 years