Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer

NCT ID: NCT00045032

Last Updated: 2017-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 5099 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2015-06-30

Brief Summary

The purpose of this trial is to evaluate Herceptin treatment for 1 year and 2 years (versus observation/no Herceptin) in women with HER2-overexpressing primary breast cancer who have completed (neo-)adjuvant systemic chemotherapy, definitive surgery, and radiotherapy, if applicable. Efficacy and safety will be assessed for 10 years from randomization for each participant. All participants will continue to be followed for survival until 10 years after enrollment of the last participant.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Observation Arm

Participants who have completed definitive surgery and systemic adjuvant chemotherapy will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin will be provided.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Herceptin 1-Year Arm

Participants who have completed definitive surgery and systemic adjuvant chemotherapy will receive Herceptin for 1 year or until disease recurrence, whichever occurs first. Participants will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.

Group Type: EXPERIMENTAL

Herceptin

Intervention Type: DRUG

Herceptin will be given as a loading dose of 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks.

Herceptin 2-Year Arm

Participants who have completed definitive surgery and systemic adjuvant chemotherapy will receive Herceptin for 2 years or until disease recurrence, whichever occurs first. Participants will be observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.

Group Type: EXPERIMENTAL

Herceptin

Intervention Type: DRUG

Herceptin will be given as a loading dose of 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks.

Interventions

Herceptin

Herceptin will be given as a loading dose of 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks.

Intervention Type: DRUG

Herceptin

Herceptin will be given as a loading dose of 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks.

Intervention Type: DRUG

Other Intervention Names

Trastuzumab; Trastuzumab

Eligibility Criteria

Inclusion Criteria

• Non-metastatic primary invasive breast cancer overexpressing HER2 (determined by immunohistochemistry 3+ or positive fluorescence in situ hybridization test) that has been histologically confirmed, adequately excised, axillary node positive or negative, and tumor size at least T1c according to Tumor/Node/Metastasis (TNM) staging
• Completion of at least 4 cycles of (neo-)adjuvant systemic chemotherapy, definitive surgery, and radiotherapy, if applicable
• Known hormone receptor status
• Baseline left ventricular ejection fraction (LVEF) greater than or equal to (≥) 55 percent (%)

Exclusion Criteria

• Prior invasive breast carcinoma
• Other malignancies except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
• Clinical T4 tumors
• Cumulative doxorubicin exposure greater than (>) 360 milligrams per meter-squared (mg/m^2) or epirubicin >720 mg/m^2 or any prior anthracyclines unrelated to the present breast cancer
• Peripheral stem cell or bone marrow stem cell support
• Prior mediastinal irradiation except for internal mammary node irradiation for the present breast cancer
• Non-irradiated internal mammary nodes or supraclavicular lymph node involvement
• Prior anti-HER2 therapy for any other reason or other prior biologic or immunotherapy for breast cancer
• Concurrent anti-cancer treatment in another investigational trial
• Serious cardiac or pulmonary conditions/illness, or any other conditions that could interfere with planned treatment
• Poor hematologic, hepatic, or renal function
• Pregnancy or lactation
• Women of childbearing potential or less than 1 year post-menopause unwilling to use adequate contraceptive measures

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Breast International Group

OTHER

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martine J. Piccart-Gebhart, MD, PhD

Role: STUDY_CHAIR

Jules Bordet Institute

Robert E. Coleman, MD, FRCP

Role: STUDY_CHAIR

Cancer Research Centre at Weston Park Hospital

Karen A. Gelmon, MD

Role: STUDY_CHAIR

British Columbia Cancer Agency

Kathleen I. Pritchard, MD

Role: STUDY_CHAIR

Toronto Sunnybrook Regional Cancer Centre

Olivia Pagani, MD

Role: STUDY_CHAIR

Ospedale Beata Vergine

Locations

Hospital Aleman de Buenos Aires

Buenos Aires, Buenos Aires, Argentina

Saint John of God Hospital

Geelong, Australian Capital Territory, Australia

Toowoomba Hospital

Toowoomba, Queensland, Australia

Andrew Love Cancer Centre

Geelong, Victoria, Australia

Mount Hospital

Perth, Western Australia, Australia

Landeskrankenhaus Feldkirch

Feldkirch-Tisis, , Austria

Innsbruck Universitaetsklinik

Innsbruck, , Austria

Landeskrankenhaus Klagenfurt

Klagenfurt, , Austria

St. Vincent's Hospital

Linz Donau, , Austria

Landeskrankenanstalten - Salzburg

Salzburg, , Austria

Landeskrankenhaus St. Poelten

Sankt Pölten, , Austria

Universitaetsklinik fuer Innere Medizin I

Vienna, , Austria

Wilhelminenspital der Stadt Wien

Vienna, , Austria

LKH Villach

Villach, , Austria

LKH Voecklabruck

Vöcklabruck, , Austria

A. oe. Krankenhaus Wiener Neustadt

Wiener Neustadt, , Austria

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Reseau Hospitalier De Medecine Sociale

Baudour, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, , Belgium

Cazk Groeninghe - Campus St-Niklaas

Kortrijk, , Belgium

Centre Hospitalier Universitaire de Tivoli

La Louvière, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Clinique Saint-Joseph

Liège, , Belgium

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, , Belgium

Clinique Sainte Elisabeth

Namur, , Belgium

Hospital Serruys Ziekenhuis

Ostend, , Belgium

Centre Hospitalier Peltzer-La Tourelle

Verviers, , Belgium

Porto Alegre Hospital

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Sao Lucas da PUCRS

Porto Alegre, , Brazil

Hospital Santa Rita

Porto Alegre, , Brazil

Instituto Nacional de Cancer

Rio de Janeiro, , Brazil

Faculdade De Medicina Do ABC

Santo André, , Brazil

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, Canada

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, Canada

Fraser Valley Cancer Centre at British Columbia Cancer Agency

Surrey, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Royal Victoria Hospital of Barrie

Barrie, Ontario, Canada

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, Canada

Trillium Health Centre - Mississauga Site

Mississauga, Ontario, Canada

Algoma Regional Cancer Program at Sault Area Hospital

Sault Ste. Marie, Ontario, Canada

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, Canada

Toronto East General Hospital

Toronto, Ontario, Canada

Mount Sinai Hospital - Toronto

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Windsor Regional Cancer Centre at Windsor Regional Hospital

Windsor, Ontario, Canada

Prince Edward Island Cancer Centre at Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

Hopital du Saint-Sacrement, Quebec

Québec, Quebec, Canada

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Fundacion Arturo Lopez Perez

Santiago, , Chile

Hospital Clinico San Borja Arriaran

Santiago, , Chile

Hospital Dr. Sotero Del Rio

Santiago, , Chile

Hospital Militar

Santiago, , Chile

Instituto Nacional Del Cancer

Santiago, , Chile

Queen Mary Hospital

Hong Kong, , China

Tuen Mun Hospital

Hong Kong, , China

Tongji Medical University

Wuhan, , China

Instituto Nacional De Cancerologia

Bogotá, , Colombia

Clinical Hospital Center Split

Split, , Croatia

Centralsygehus I Esbjerg

Esbjerg, , Denmark

Herning Central Hospital

Herning, , Denmark

Hillerod Hospital

Hillerød, , Denmark

Centralsygehuset I Naestved

Næstved, , Denmark

Sonderborg Sygehus

Sønderborg, , Denmark

Centre Regional Francois Baclesse

Caen, , France

Centre Hospital Regional Universitaire de Limoges

Limoges, , France

Hopital Clinique Claude Bernard

Metz, , France

Charite - Campus Charite Mitte

Berlin, , Germany

Evangelisches Bethesda Krankenhaus GmbH

Essen, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Martin Luther Universitaet

Halle, , Germany

Henriettenstiftung Krankenhaus

Hanover, , Germany

Universitaets-Hautklinik Heidelberg

Heidelberg, , Germany

St. Vincentius-Kliniken

Karlsruhe, , Germany

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, , Germany

Kreiskrankenhaus Leonberg - Frauenklinik

Leonberg, , Germany

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, , Germany

Frauenklinik Vom Roten Kreuz

Munich, , Germany

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, , Germany

Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt

Rostock, , Germany

Universitaet Ulm

Ulm, , Germany

Dr. Horst-Schmidt-Kliniken

Wiesbaden, , Germany

University of Crete School of Medicine

Heraklion, Crete, Greece

Evaggelismos Hospital

Athens, , Greece

Centro Medico

Guatemala City, , Guatemala

Hospital Roosevelt

Guatemala City, , Guatemala

Prince of Wales Hospital

Shatin, New Territories, , Hong Kong

Semmelweis University

Budapest, , Hungary

National Institute of Oncology

Budapest, , Hungary

Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia

Budapest, , Hungary

Cork University Hospital

Cork, , Ireland

Sieff Hospital

Safed, , Israel

Ospedale San Lazzaro

Alba, , Italy

Ospedale Presenti Fenaroli

Alzano Lombardo, , Italy

Centro di Riferimento Oncologico - Aviano

Aviano, , Italy

Ospedali Riuniti di Bergamo

Bergamo, , Italy

Ospedale degli Infermi - ASL 12

Biella, , Italy

Ospedale Bellaria

Bologna, , Italy

Spedali Civili di Brescia

Brescia, , Italy

Ospedale Oncologico A. Businco

Cagliari, , Italy

Ospedale B. Ramazzini

Carpi, , Italy

Ospedale Valduce

Como, , Italy

Ospedale Santa Croce

Cuneo, , Italy

Universita Degli Studi Di Florence

Firenze (Florence), , Italy

Azienda Ospedaliero Careggi

Florence, , Italy

Morgagni-Pierantoni Ospedale

Forlì, , Italy

Istituto Nazionale per la Ricerca sul Cancro

Genoa, , Italy

Ospedale A. Manzoni

Lecco, , Italy

Presidio Ospedaliero

Livorno, , Italy

Carlo Poma Hospital

Mantova, , Italy

European Institute of Oncology

Milan, , Italy

Ospedale Niguarda Ca'Granda

Milan, , Italy

University of Modena Hospital and Reggio Emilia School of Medicine

Modena, , Italy

Azienda Ospedaliera Di Parma

Parma, , Italy

I.R.C.C.S. Policlinico San Matteo

Pavia, , Italy

Policlinico Monteluce

Perugia, , Italy

Azienda Ospedaliera

Reggio Emilia, , Italy

Ospedale San Filippo Neri

Rome, , Italy

Ospedale Sant' Eugenio

Rome, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

Ospedale Civile ASL 1

Sassari, , Italy

Primario U.O. di Oncologia Medica

Trento, , Italy

Ospedale Ostetrico Ginecologica Sant Anna

Turin, , Italy

Universita di Torino

Turin, , Italy

Tokai University School Of Medicine

Kanagawa, , Japan

Tokyo Metropolitan - Komagome Hospital

Tokyo, , Japan

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Maasland Hospital

Sittard, , Netherlands

Diakonessenhuis Utrecht

Utrecht, , Netherlands

Medical University of Gdansk

Gdansk, , Poland

Oncologic Center

Gliwice, , Poland

Medical University

Poznan, , Poland

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

Instituto Portugues de Oncologia, Centro Regional de Coimbra

Coimbra, , Portugal

Hospitais da Universidade de Coimbra (HUC)

Coimbra, , Portugal

Maternidade Byssaia Barreto

Coimbra, , Portugal

Hospital Distrital De Faro

Faro, , Portugal

Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.

Lisbon, , Portugal

University Hospital of Santa Maria

Lisbon, , Portugal

Moscow Oncology Hospital

Moscow, , Russia

P.A. Hertzen Research Oncology Institute

Moscow, , Russia

Johns Hopkins Singapore International Medical Centre

Singapore, , Singapore

Groote Schuur Hospital

Cape Town, , South Africa

Parklands Hospital

Durban, , South Africa

Sandton Oncology Centre

Johannesburg, , South Africa

Medical Oncology Centre of Rosebank

Johannesburg, , South Africa

Pretoria - East Hospital

Lynnwood, , South Africa

Seoul National University Hospital

Seoul, , South Korea

Yonsei Cancer Center at Yonsei University Medical Center

Seoul, , South Korea

Centro Oncologico De Galicia Jose Antonio Quirogay Pineyro

A Coruña, , Spain

Hospital De La Ribera

Alzira, , Spain

Hospital Del Mar

Barcelona, , Spain

Hospital Universitario San Cecilio de Granada

Granada, , Spain

Hospital General Universitario De Guadalajara

Guadalajara, , Spain

Hospital Juan Ramon Jimenez

Huelva, , Spain

Hospital Cuidad de Jaen

Jaén, , Spain

Hospital Insular de Gran Canaria

Las Palmas, , Spain

Hospital de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, , Spain

Hospital de la Princesa

Madrid, , Spain

Complejo Hospitalario Santa Maria

Ourense, , Spain

Complejo Hospitalario de Pontevedra

Pontevedra, , Spain

Consorci Hospitalari del Parc Tauli

Sabadell, , Spain

Hospital Universitario Canarias

San Cristóbal de La Laguna, , Spain

Hospital Universitario Nuestra Senora de la Candelaria

Santa Cruz de Tenerife, , Spain

Hospital Universidad Virgen Del Rocio

Seville, , Spain

Hospital Virgen Del La Salud

Toledo, , Spain

Hospital General Universitario Valencia

Valencia, , Spain

Complexo Hospitalario Xeral de Vigo

Vigo Pontevedra, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

University Hospital of Linkoping

Linköping, , Sweden

University Hospital of Malmoe

Malmo, , Sweden

Sahlgrenska University Hospital - Molndal at Gothenburg University

Mölndal, , Sweden

Karolinska University Hospital - Huddinge

Stockholm, , Sweden

Umea Universitet

Umeå, , Sweden

Uppsala University Hospital

Uppsala, , Sweden

Kantonspital Aarau

Aarau, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitaeler Chur AG

Chur, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Ospedale Beata Vergine

Mendrisio, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Chulalongkorn University Hospital

Bangkok, , Thailand

Ramathibodi Hospital

Bangkok, , Thailand

Bradford Hospitals NHS Trust

Bradford, England, United Kingdom

Broomfield Hospital

Chelmsford, Essex, England, United Kingdom

Saint Margaret's Hospital

Epping Essex, England, United Kingdom

Diana Princess of Wales Hospital

Grimsby, England, United Kingdom

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, United Kingdom

Princess Royal Hospital

Hull, England, United Kingdom

Cookridge Hospital at Leeds Teaching Hospital NHS Trust

Leeds, England, United Kingdom

Imperial College of Medicine

London, England, United Kingdom

James Cook University Hospital

Middlesbrough, England, United Kingdom

Northern Centre for Cancer Treatment at Newcastle General Hospital

Newcastle upon Tyne, England, United Kingdom

Cancer Research Centre at Weston Park Hospital

Sheffield, England, United Kingdom

Airedale General Hospital

West Yorkshire, England, United Kingdom

Southend NHS Trust Hospital

Westcliff-on-Sea, England, United Kingdom

Countries

Argentina; Australia; Austria; Belgium; Brazil; Canada; Chile; China; Colombia; Croatia; Denmark; France; Germany; Greece; Guatemala; Hong Kong; Hungary; Ireland; Israel; Italy; Japan; Netherlands; Poland; Portugal; Russia; Singapore; South Africa; South Korea; Spain; Sweden; Switzerland; Thailand; United Kingdom

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Other Identifiers

BIG-01-01

Identifier Type: -

Identifier Source: secondary_id

EU-20216

Identifier Type: -

Identifier Source: secondary_id

ROCHE-B016348E

Identifier Type: -

Identifier Source: secondary_id

ROCHE-B016348C

Identifier Type: -

Identifier Source: secondary_id

EORTC-10011

Identifier Type: -

Identifier Source: secondary_id

CAN-NCIC-MA24

Identifier Type: -

Identifier Source: secondary_id

IBCSG-28-02

Identifier Type: -

Identifier Source: secondary_id

BO16348

Identifier Type: -

Identifier Source: org_study_id