A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)

Breast Cancer Clinical Trial

Official title:

A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy for Patients With HER2-Positive Primary Breast Cancer Who Have Residual Tumor Present Pathologically in the Breast or Axillary Lymph Nodes Following Preoperative Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01772472
• Other study ID #: BO27938
• Secondary ID: 2012-002018-37
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 3, 2013
• Est. completion date: May 15, 2024

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This 2-arm, randomized, open-label study will evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. Radiotherapy and/or hormone therapy will be given in addition if indicated.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1487
• Est. completion date: May 15, 2024
• Est. primary completion date: July 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patient, >/= 18 years of age
• HER2-positive breast cancer
• Histologically confirmed invasive breast carcinoma
• Clinical stage T1-4/N0-3/M0 at presentation (patients with T1a/bN0 tumors will not be eligible)
• Completion of preoperative systemic chemotherapy and HER2-directed treatment consisting of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based therapy
• Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as specified in protocol
• Pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy
• An interval of no more than 12 weeks between the date of surgery and the date of randomization
• Known hormone-receptor status
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate hematologic, renal and liver function
• Screening Left ventricular ejection fraction (LVEF) >/= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >/= 55% after completion of neoadjuvant chemotherapy.
• For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drug
• Documentation of hepatitis B virus and hepatitis C virus serology is required

Exclusion Criteria:

• Stage IV (metastatic) breast cancer
• History of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in situ
• Evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery
• Progressive disease during preoperative systemic therapy
• Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment
• History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with a similar outcome to those mentioned above
• Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons
• Current NCI CTCAE (Version 4.0) Grade >/= 2 peripheral neuropathy
• History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) > 480 mg/m2; For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2
• Cardiopulmonary dysfunction as defined by protocol
• Prior treatment with trastuzumab emtansine
• Current severe, uncontrolled systemic disease
• Pregnant or lactating women
• Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis
• Concurrent serious uncontrolled infections requiring treatment or known infection with HIV
• History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neoplasm, Residual

Intervention

Drug:
• trastuzumab
6 mg/kg intravenously every 3 weeks, 14 cycles
• trastuzumab emtansine
3.6 mg/kg intravenously every 3 weeks, 14 cycles

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Argentina	Instituto de Oncología de Rosario	Rosario
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie	Innsbruck
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	Cliniques Universitaires St-Luc	Bruxelles
Belgium	AZ Sint Lucas (Sint Lucas)	Gent
Belgium	CHU Sart-Tilman	Liège
Belgium	Sint Augustinus Wilrijk	Wilrijk
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Iop Instituto de Oncologia Do Parana	Curitiba	PR
Brazil	UPCO - Unidade de Pesquisas Clínicas em Oncologia	Pelotas	RS
Brazil	Hospital Moinhos de Vento	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Clinicas Oncologicas Integradas - COI	Rio De Janeiro	RJ
Brazil	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ
Brazil	Hospital Perola Byington	Sao Paulo	SP
Brazil	Hospital Sao Jose	Sao Paulo	SP
Brazil	Instituto de Ensino e Pesquisa Sao Lucas - IEP	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	Tom Baker Cancer Centre; Dept of Medicine	Calgary	Alberta
Canada	Cross Cancer Institute ; Dept of Medical Oncology	Edmonton	Alberta
Canada	CSSS champlain - Charles-Le Moyne	Greenfield Park	Quebec
Canada	London Regional Cancer Centre	London	Ontario
Canada	Centre Hospitalier de l?Université de Montréal (CHUM)	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Health Centre - Glen Site	Montreal	Quebec
Canada	The Ottawa Hospital; Division of Infectious Diseases	Ottawa	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Canada	BC Cancer ? Surrey	Surrey	British Columbia
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Canada	British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre	Vancouver	British Columbia
China	the First Hospital of Jilin University	Changchun
China	Guangdong General Hospital	Guangzhou
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Shandong Cancer Hospital	Jinan
China	Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
Colombia	Clinica del Country	Bogota
Colombia	Hospital Pablo Tobon Uribe	Medellin
Colombia	Oncomedica S.A.	Monteria
Czechia	Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	Institut Sainte Catherine;Recherche Clinique	Avignon
France	HOPITAL JEAN MINJOZ; Oncologie	Besancon
France	Institut Bergonie; Oncologie	Bordeaux
France	Centre Hospitalier Fleyriat; Oncologie/Hematologie	Bourg En Bresse
France	Centre Francois Baclesse; Comite Sein	Caen
France	Centre Jean Perrin; Oncologie	Clermont Ferrand
France	Centre de Cancerologie de la Sarthe, Clinique Victor Hugo SoReCOH	Le Mans
France	Institut Paoli Calmettes; Oncologie Medicale	Marseille
France	Centre Val Aurelle Paul Lamarque; Recherche Clinique	Montpellier
France	Hopital Saint Louis; Oncologie Medicale	Paris
France	HOPITAL TENON; Cancerologie Medicale	Paris
France	Institut Curie; Oncologie Medicale	Paris
France	Centre Henri Becquerel; Oncologie Medicale	Rouen
France	Centre Rene Huguenin; CONSULT SPECIALISEES	St Cloud
France	Centre Paul Strauss; Oncologie Medicale	Strasbourg
France	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif
Germany	Hämatologie Onkologie im Zentrum MVZ GmbH	Augsburg
Germany	HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe	Berlin
Germany	Onkologische Schwerpunktpraxis Kurfürstendamm	Berlin
Germany	Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)	Berlin
Germany	Studienzentrum Berlin City	Berlin
Germany	Onkologische Schwerpunktpraxis Bielefeld	Bielefeld
Germany	Klinikum Sindelfingen-Böblingen; Frauenklinik	Böblingen
Germany	St. Johannes-Hospital	Dortmund
Germany	Luisenkrankenhaus GmbH & Co. KG., Brustzentrum	Düsseldorf
Germany	Universitätsklinikum Erlangen; Frauenklinik	Erlangen
Germany	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen
Germany	Universitätsklinikum Essen; Zentrum Für Frauenheilkunde	Essen
Germany	Klinikum Esslingen; Klinik für Frauenheilkunde und Geburtshilfe	Esslingen
Germany	Klinik Johann Wolfgang von Goethe Uni; Klinik für Frauenheilkunde und Geburtshilfe	Frankfurt
Germany	Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus	Frankfurt am Main
Germany	Universitätsklinikum Freiburg; Frauenklinik	Freiburg
Germany	Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum	Gelsenkirchen
Germany	Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum	Greifswald
Germany	Krankenhaus St. Elisabeth und St. Barbara, Klinik für Frauenheilkunde und Geburtshilfe	Halle
Germany	Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie	Halle
Germany	Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem	Hamburg
Germany	St. Barbara-Klinik Hamm-Heessen GmbH; Frauenklinik	Hamm
Germany	Diakovere Henriettenstift, Frauenklinik	Hannover
Germany	Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe	Hannover
Germany	MVZ Onko Medical GmbH Hannover, Ralf Lohse (Geschäftsführer)	Hannover
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	Elisabeth-Krankenhaus Brustzentrum	Kassel
Germany	Klinikum Kassel GmbH; Klinik für Frauenheilkunde und Geburtshilfe	Kassel
Germany	UNI-Klinikum Campus Kiel Klinik für Gynäkologie und Geburtshilfe	Kiel
Germany	St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe	Koeln
Germany	Kliniken der Stadt Köln gGmbH Krankenhaus Holweide; Brustzentrum	Köln
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie, PD Dr. Bauer, Dr. Thiel	Lebach
Germany	Klinikum der Universität München; Frauenklinik - Onkologie II	München
Germany	Medizinisches Zentrum für Hämatologie und Onkologie	München
Germany	MVZ Nordhausen gGmbH, Praxis Dr. Grafe	Nordhausen
Germany	Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe	Offenbach
Germany	St. Vincenz-Krankenhaus Paderborn; Haus 3 Frauenklinik	Paderborn
Germany	Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie	Recklinghausen
Germany	Klinikum am Steinenberg Frauenklinik	Reutlingen
Germany	Universitätsfrauen- und Poliklinik am Klinikum Suedstadt	Rostock
Germany	Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher	Stralsund
Germany	Robert-Bosch-Krankenhaus; Brustzentrum	Stuttgart
Germany	Gemeinschaftspraxis Dr. Kronawitter und Dr. Jung	Traunstein
Germany	Universitätsklinik Tübingen; Frauenklinik	Tübingen
Germany	Universitätsklinikum Ulm Am Michelsberg; Frauenklinik	Ulm
Germany	HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie	Wiesbaden
Germany	Marien-Hospital Witten; Frauenklinik Brustzentrum	Witten
Germany	Hämatologisch-Onkologische Schwerpunktpraxis Dres. Schlag & Schöttker	Würzburg
Greece	Univ General Hosp Heraklion; Medical Oncology	Heraklion
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Guatemala	Centro Oncológico Sixtino / Centro Oncológico SA	Guatemala
Guatemala	Grupo Angeles	Guatemala City
Hong Kong	Pamela Youde Nethersole Eastern Hospital; Clinical Oncology	Hong Kong
Hong Kong	Queen Mary Hospital; Surgery	Hong Kong
Hong Kong	Tuen Mun Hospital; Clinical Oncology	Hong Kong
Ireland	Cork Uni Hospital; Oncology Dept	Cork
Ireland	Beaumont Hospital; Cancer Clinical Trials Unit	Dublin
Ireland	Mater Misericordiae Uni Hospital; Oncology	Dublin
Ireland	St Vincent'S Uni Hospital; Medical Oncology	Dublin
Ireland	Galway Uni Hospital; Oncology Dept	Galway
Ireland	University Hospital Limerick - Oncology	Limerick
Israel	Soroka Medical Center	Beer Sheva
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Shaare Zedek Medical Center; Oncology Dept	Jerusalem
Israel	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva
Israel	Sheba Medical Center; Tel Hashomer	Ramat Gan
Israel	Kaplan Medical Center; Oncology Inst.	Rehovot
Italy	Asst Papa Giovanni XXIII; Oncologia Medica	Bergamo	Lombardia
Italy	Ausl Di Bologna-Ospedale Bellaria;U.O. Oncologia Medica	Bologna	Emilia-Romagna
Italy	Policlinico S.Orsola-Malpighi; Istituto Oncologia R. Addarii	Bologna	Emilia-Romagna
Italy	Ospedale Antonio Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo	Candiolo	Piemonte
Italy	ASST DI CREMONA; Unità di Patologia Mammaria Senologia e Breast Unit	Cremona	Lombardia
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	ASST DI MONZA; Oncologia Medica	Monza	Lombardia
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania
Italy	Università degli Studi Federico II; Clinica di Oncologia Medica	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2	Pisa	Toscana
Italy	Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia	Pontedera	Toscana
Italy	Az. Osp. Sant'Andrea; Oncologia Medica	Roma	Lazio
Italy	Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica	Roma	Lazio
Italy	A.O.U.I. VERONA-OSPEDALE BORGO TRENTO; ONCOLODIA MEDICA-d.O.	Verona	Veneto
Mexico	Médicos Especialistas en Cáncer SC	Aguascalientes
Mexico	Hospital Angeles Metropolitano; Room 220	Mexico City	Mexico CITY (federal District)
Mexico	Instituto Nacional de Cancerologia; Oncology	Mexico City
Mexico	Nstituto Nacional de Ciancias Medicas Y Nutricion, Salvador Zubir	Mexico City	Mexico CITY (federal District)
Mexico	Oaxaca Site Management Organization	Oaxaca de Juárez	Oaxaca
Panama	Centro Oncologico America	Panama
Panama	The Panama Clinic	Panama
Peru	Centro Medico Monte Carmelo	Arequipa
Peru	Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology	Arequipa
Peru	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista
Peru	Clinica San Borja	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen; Oncology	Lima
Serbia	Institute for Oncology and Radiology of Serbia; Clinic for Medical Oncology	Belgrade
Serbia	Oncology Institute of Vojvodina	Sremska Kamenica
South Africa	Cape Town Oncology Trials	Cape Town
South Africa	Hopelands Cancer Centre	Hilton
South Africa	Medical Oncology Centre of Rosebank; Oncology	Johannesburg
South Africa	Wits Donald Gordon Clinical Trial Centre; Medical Oncology	Johannesburg
South Africa	Cancercare	Port Elizabeth
South Africa	Private Oncology Centre	Pretoria
Spain	Hospital Clínic i Provincial; Servicio de Oncología	Barcelona
Spain	Hospital Severo Ochoa; Servicio de Oncologia	Leganes	Madrid
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Hospital de Navarra; Servicio de Oncologia	Navarra
Spain	Hospital Universitari Sant Joan de Reus; Servicio de Oncologia	Reus	Tarragona
Spain	Hospital Clinico Universitario de Salamanca; Servicio de Oncologia	Salamanca
Spain	Hospital de Donostia; Servicio de Oncologia Medica	San Sebastian	Guipuzcoa
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario Dr. Peset; Servicio de Oncologia	Valencia
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Spain	Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro; Servicio de Oncología	Vigo	Pontevedra
Sweden	Gävle Sjukhus; Onkologiska Kliniken	Gävle
Sweden	Skånes University Hospital, Skånes Department of Onclology	Lund
Sweden	Karolinska Hospital; Oncology - Radiumhemmet	Stockholm
Switzerland	Kantonsspital Aarau AG Medizin Onkologie; ZENTRUM FÜR ONKOLOGIE, HÄMATOLOGIE & TRANSFUSIONSMEDIZIN	Aarau
Switzerland	Brust-Zentrum Zürich AG Seefeldstrasse 214 Zürich	Zürich
Taiwan	Taichung Veterans General Hospital; Dept of Surgery	Taichung
Taiwan	National Taiwan Uni Hospital; General Surgery	Taipei
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology	Taipei City
Taiwan	Chang Gung Medical Foundation - Linkou; Dept of Surgery	Taoyuan
Turkey	Uludag Uni Hospital; Oncology	Bursa
Turkey	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne
Turkey	Kartal Dr Lutfi Kirdar Sehir Hastanesi; Medical Oncology Department	Istanbul
Turkey	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir
Turkey	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya
United Kingdom	University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital	Birmingham
United Kingdom	Bradford Royal Infirmary; Dept of Medical Oncology C/O Ward15	Bradford
United Kingdom	Bristol Haematology and Oncology centre	Bristol
United Kingdom	Royal Cornwall Hospital; Dept of Clinical Oncology	Cornwall
United Kingdom	Castle Hill Hospital; The Queens Centre for Oncology and Haematology	Cottingham
United Kingdom	North Devon District Hospital	Devon
United Kingdom	Ninewells Hospital; Cancer Medicine	Dundee
United Kingdom	Huddersfield Royal Infirmary	Huddersfield
United Kingdom	Leeds Teaching Hosp NHS Trust;St James's Institute of Onc	Leeds
United Kingdom	Charing Cross Hospital; Medical Oncology.	London
United Kingdom	St Thomas Hospital; Medicine Div.	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United Kingdom	Nottingham City Hospital; Oncology	Nottingham
United Kingdom	Weston Park Hospital	Sheffield
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Med Star Franklin Square Medical Center/Weinburg Cancer Institute	Baltimore	Maryland
United States	Mercy Medical Center; Medical Oncology & Hematology	Baltimore	Maryland
United States	Cancer Care of Maine	Brewer	Maine
United States	Aultman Hospital; Aultman Hospital Cancer Center	Canton	Ohio
United States	Medical University of South Carolina; Hollings Cancer Center	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Fairview Hospital; Cleveland Clinic Cancer Center	Cleveland	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University, Arthur James Cancer Hospital	Columbus	Ohio
United States	Batte Cancer Center - Carolinas Medical Center	Concord	North Carolina
United States	Colorado Cancer Research Program/Admin	Denver	Colorado
United States	Kaiser Permanente - Franklin	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Hematology Oncology Associates of Fredericksburg, Inc.	Fredericksburg	Virginia
United States	University of Florida; Davis Cancer Pavilion and Shands Medical Plaza	Gainesville	Florida
United States	Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Hartford Hospital	Hartford	Connecticut
United States	Baylor College of Medicine	Houston	Texas
United States	Houston Methodist Hospital Outpatient Center	Houston	Texas
United States	Uni of Texas - Md Anderson Cancer Center; Dept of Breast Medical Oncology	Houston	Texas
United States	Swedish Cancer Institute - Issaquah	Issaquah	Washington
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Breslin Cancer Center	Lansing	Michigan
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Rocky Mountain Cancer Centers - Colorado Springs (Circle)	Lone Tree	Colorado
United States	Todd Cancer Institute at Long Beach Memorial Medical Center	Long Beach	California
United States	PeaceHealth St. John Medical Center - Lower Columbia Cancer Center	Longview	Washington
United States	Norton Healthcare Inc.	Louisville	Kentucky
United States	University of Iowa	Lowa City	Iowa
United States	Joe Arrington Cancer Research & Treatment Center	Lubbock	Texas
United States	Lynchburg Hem Onc Clinic Inc	Lynchburg	Virginia
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Lake Health/University Hospitals - Mentor Campus	Mentor	Ohio
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Edward Cancer Center Naperville	Naperville	Illinois
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale Cancer Center	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Chao Family Comprehensive Cancer Center; UC Irvine Medical Center	Orange	California
United States	UF Health Orlando	Orlando	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	Kimmel Cancer Center Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Allegheny Cancer Center	Pittsburgh	Pennsylvania
United States	Uni of Pittsburgh; Magee-Women'S Hospital	Pittsburgh	Pennsylvania
United States	Edward Cancer Center Plainfield	Plainfield	Illinois
United States	Columbia River Oncology Program	Portland	Oregon
United States	Virginia Commonwealth University - Massey Cancer Center	Richmond	Virginia
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	US oncology research at Minnesota Oncology	Saint Paul	Minnesota
United States	Kaiser Permanente - San Diego	San Diego	California
United States	Breastlink Medical Group Inc	Santa Ana	California
United States	New England Cancer Specialists	Scarborough	Maine
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sparta Cancer Center	Sparta	New Jersey
United States	Cancer Care Northwest	Spokane	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Troy Cancer Treatment Program	Troy	New York
United States	Kaiser Permanente - Vallejo	Vallejo	California
United States	Washington Cancer Institute; Washington Hospital Center	Washington	District of Columbia
United States	York Hospital	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Hoffmann-La Roche	German Breast Group, NSABP Foundation Inc

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  China,  Colombia,  Czechia,  France,  Germany,  Greece,  Guatemala,  Hong Kong,  Ireland,  Israel,  Italy,  Mexico,  Panama,  Peru,  Serbia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive Disease-free Survival (IDFS)	IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.	From randomization to data cut-off date of 25 July 2018 (approximately up to 64 months)
Secondary	Invasive Disease-free Survival Including Second Primary Non-breast Cancer	IDFS including second primary non-breast cancer was defined the same way as IDFS for the primary endpoint but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ (CIS) of any site). 3-year IDFS including second primary non-breast cancer event-free rates per treatment arm in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.	From baseline up to 12 years
Secondary	Disease-free Survival	Disease-free survival was defined as the time between randomization and the date of the first occurrence of an invasive disease-free survival event including second primary non-breast cancer event or contralateral or ipsilateral DCIS. 3-year DFS event-free rates per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.	From baseline up to 12 years
Secondary	Overall Survival (OS)	Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 5 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 5 years after treatment.	Baseline up to 12 years
Secondary	Distant Recurrence-Free Interval (DRFI)	DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 3 years DRFI event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment.	Baseline up to 12 years
Secondary	Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest and AEs of Particular Interest, were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).	From Day 1 to 30 days after last dose of study drug, up to the clinical cutoff date (approximately 64 months)
Secondary	Percentage of Participants With Cardiac Dysfunction	Cardiac events were reported based on the NCI-CTCAE, v4.0.	From baseline up to 12 years
Secondary	Change From Baseline of Functional Scales, Symptom Scales and Single Items in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)	The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).	Baseline, Cycle 5, 11, Follow-up (FU) Month 6, Follow-up Month 12
Secondary	Change From Baseline of Four Functioning Scales and Four Symptom Scales in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Breast Cancer (QLQ-BR23)	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated deterioration in quality of life (QOL) and negative change from baseline indicated an improvement in QOL. For symptom scales, positive change from baseline indicated an improvement in quality of life (QOL) and negative change from baseline indicated a deterioration in QOL.	Baseline, Cycle 5, 11, Follow-up Month 6, Follow-up Month 12
Secondary	Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine (Including Total Trastuzumab and DM1)	Blood and serum samples for measurement of trastuzumab emtansine, total trastuzumab, and DM1 will be obtained from patients randomized to the trastuzumab emtansine arm.	Cycle (C) 1, Day (D) 1 and C4D1 of pre-infusion, C1D1 and C4D1 post-infusion, C2D1 and C5D1 pre-infusion and study treatment termination
Secondary	Serum Concentrations (AUC) of Trastuzumab	Serum blood samples were collected for trastuzumab measurement prior to dosing and 15-30 minutes post infusion for Cycle 1 and Cycle 4. Additional serum samples were collected at study treatment termination.	C1D1 and C4D1 of post-infusion and study treatment termination
Secondary	Plasma Concentrations of DM1		Day 1 on Cycles 1 and 4. Each cycle is 21 days.
Secondary	Trastuzumab Emtansine Exposure		Day 1 on Cycles 1, 2, 4 and 5, at study treatment termination and 3-4 months after last dose of trastuzumab emtansine. Each cycle is 21 days.
Secondary	Anti-trastuzumab Emtansine Antibody (ATA)		Day 1 on Cycles 1, and 4, at study treatment termination and 3-4 months after last dose of trastuzumab emtansine. Each cycle is 21 days.
Secondary	Anti-trastuzumab Antibody (ATA)		Day 1 on Cycles 1, and 4, at study treatment termination and 3-4 months after last dose of trastuzumab emtansine. Each cycle is 21 days.