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

NCT00045032 | Completed Phase 3 Results

• 8 other identifiers: BO16348BIG-01-01EU-20216ROCHE-B016348EROCHE-B016348CEORTC-10011CAN-NCIC-MA24IBCSG-28-02
• Study Type: interventional
• Target: 5,099
• Locations: 32 countries
• Sites: 192

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

Outcome Measures

Primary Outcomes (16)

• Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an Independent Data Monitoring Committee (IDMC) in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

  From Baseline until time of event (median of 1 year)

• Percentage of Participants With DFS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.

  From Baseline until time of event (median of 1 year)

• DFS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95 percent (%) confidence interval (CI) were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

  Year 2

• DFS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.

  Year 2

• Percentage of Participants With DFS Events Compared to Observation: 8-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.

  From Baseline until time of event (median of 8 years)

• DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

  Year 3

• DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

  Year 5

• DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

  Year 7

• DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

  Year 8

• Percentage of Participants With DFS Events Compared to Observation: 10-Year Maximum Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.

  From Baseline until time of event (maximum of 10 years)

• DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

  Year 3

• DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

  Year 5

• DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

  Year 7

• DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

  Year 8

• DFS Rate at Year 9 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

  Year 9

• DFS Rate at Year 10 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up

  DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

  Year 10

Secondary Outcomes (32)

• Percentage of Participants With DFS Events in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up

  From Baseline until time of event (maximum of 10 years)

• DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up

  Years 3, 5, 7, 8, 9, 10

• Percentage of Participants With Overall Survival (OS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up

  From Baseline until time of event (median of 1 year)

• Percentage of Participants With OS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up

  From Baseline until time of event (median of 1 year)

• OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up

  Year 2

Study Arms (3)

Observation Arm

NO INTERVENTION

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.

Herceptin 1-Year Arm

EXPERIMENTAL

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.

Drug: Herceptin

Herceptin 2-Year Arm

EXPERIMENTAL

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.

Drug: Herceptin

Interventions

Herceptin 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.

Also known as: Trastuzumab

Herceptin 1-Year Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (%)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Breast International Group: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• NCIC Clinical Trials Group: collaborator
• ETOP IBCSG Partners Foundation: collaborator

Study Sites (203)

Hospital Aleman de Buenos Aires

Buenos Aires, Buenos Aires, 1118, Argentina

Location

Saint John of God Hospital

Geelong, Australian Capital Territory, 3220, Australia

Location

Toowoomba Hospital

Toowoomba, Queensland, 4350, Australia

Location

Andrew Love Cancer Centre

Geelong, Victoria, 3220, Australia

Location

Mount Hospital

Perth, Western Australia, 6000, Australia

Location

Landeskrankenhaus Feldkirch

Feldkirch-Tisis, 6807, Austria

Location

Innsbruck Universitaetsklinik

Innsbruck, A-6020, Austria

Location

Landeskrankenhaus Klagenfurt

Klagenfurt, 9026, Austria

Location

St. Vincent's Hospital

Linz Donau, A-4010, Austria

Location

Landeskrankenanstalten - Salzburg

Salzburg, A-5020, Austria

Location

Landeskrankenhaus St. Poelten

Sankt Pölten, 3100, Austria

Location

Universitaetsklinik fuer Innere Medizin I

Vienna, 1090, Austria

Location

Wilhelminenspital der Stadt Wien

Vienna, A-1160, Austria

Location

LKH Villach

Villach, 9500, Austria

Location

LKH Voecklabruck

Vöcklabruck, 4840, Austria

Location

A. oe. Krankenhaus Wiener Neustadt

Wiener Neustadt, A-2700, Austria

Location

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, 2020, Belgium

Location

Reseau Hospitalier De Medecine Sociale

Baudour, 7331, Belgium

Location

Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, 1090, Belgium

Location

Institut Jules Bordet

Brussels, B-1000, Belgium

Location

Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, 6000, Belgium

Location

Cazk Groeninghe - Campus St-Niklaas

Kortrijk, B-8500, Belgium

Location

Centre Hospitalier Universitaire de Tivoli

La Louvière, 7100, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Clinique Saint-Joseph

Liège, B 4000, Belgium

Location

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, B-4000, Belgium

Location

Clinique Sainte Elisabeth

Namur, 5000, Belgium

Location

Hospital Serruys Ziekenhuis

Ostend, 8400, Belgium

Location

Centre Hospitalier Peltzer-La Tourelle

Verviers, B-4800, Belgium

Location

Porto Alegre Hospital

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Hospital Sao Lucas da PUCRS

Porto Alegre, 90610-000, Brazil

Location

Hospital Santa Rita

Porto Alegre, 91330-490, Brazil

Location

Instituto Nacional de Cancer

Rio de Janeiro, 20560-120, Brazil

Location

Faculdade De Medicina Do ABC

Santo André, 09060-650, Brazil

Location

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

Fraser Valley Cancer Centre at British Columbia Cancer Agency

Surrey, British Columbia, V3V 1Z2, Canada

Location

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Royal Victoria Hospital of Barrie

Barrie, Ontario, L4M 6M2, Canada

Location

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Trillium Health Centre - Mississauga Site

Mississauga, Ontario, L5B 1B8, Canada

Location

Algoma Regional Cancer Program at Sault Area Hospital

Sault Ste. Marie, Ontario, P6A 2C4, Canada

Location

Hotel Dieu Health Sciences Hospital - Niagara

St. Catharines, Ontario, L2R 5K3, Canada

Location

Toronto East General Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

Mount Sinai Hospital - Toronto

Toronto, Ontario, M5G 1X5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Windsor Regional Cancer Centre at Windsor Regional Hospital

Windsor, Ontario, N8W 2X3, Canada

Location

Prince Edward Island Cancer Centre at Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

Hopital du Saint-Sacrement, Quebec

Québec, Quebec, G1S 4L8, Canada

Location

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Fundacion Arturo Lopez Perez

Santiago, 29, Chile

Location

Hospital Clinico San Borja Arriaran

Santiago, Chile

Location

Hospital Dr. Sotero Del Rio

Santiago, Chile

Location

Hospital Militar

Santiago, Chile

Location

Instituto Nacional Del Cancer

Santiago, Chile

Location

Queen Mary Hospital

Hong Kong, China

Location

Tuen Mun Hospital

Hong Kong, China

Location

Tongji Medical University

Wuhan, 430030, China

Location

Instituto Nacional De Cancerologia

Bogotá, Colombia

Location

Clinical Hospital Center Split

Split, 21000, Croatia

Location

Centralsygehus I Esbjerg

Esbjerg, 6700, Denmark

Location

Herning Central Hospital

Herning, 7400, Denmark

Location

Hillerod Hospital

Hillerød, 3400, Denmark

Location

Centralsygehuset I Naestved

Næstved, 4700, Denmark

Location

Sonderborg Sygehus

Sønderborg, 6400, Denmark

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

Centre Hospital Regional Universitaire de Limoges

Limoges, 87042, France

Location

Hopital Clinique Claude Bernard

Metz, 57072, France

Location

Charite - Campus Charite Mitte

Berlin, D-10117, Germany

Location

Evangelisches Bethesda Krankenhaus GmbH

Essen, D-45355, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, D-79106, Germany

Location

Martin Luther Universitaet

Halle, D-06097, Germany

Location

Henriettenstiftung Krankenhaus

Hanover, D-30559, Germany

Location

Universitaets-Hautklinik Heidelberg

Heidelberg, D-69115, Germany

Location

St. Vincentius-Kliniken

Karlsruhe, D-76137, Germany

Location

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, D-24105, Germany

Location

Kreiskrankenhaus Leonberg - Frauenklinik

Leonberg, D-71229, Germany

Location

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, D-39120, Germany

Location

Frauenklinik Vom Roten Kreuz

Munich, 80637, Germany

Location

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, D-81675, Germany

Location

Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt

Rostock, D-18059, Germany

Location

Universitaet Ulm

Ulm, D-89075, Germany

Location

Dr. Horst-Schmidt-Kliniken

Wiesbaden, D-65199, Germany

Location

University of Crete School of Medicine

Heraklion, Crete, 71110, Greece

Location

Evaggelismos Hospital

Athens, 10676, Greece

Location

Centro Medico

Guatemala City, 01010, Guatemala

Location

Hospital Roosevelt

Guatemala City, 01010, Guatemala

Location

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

Semmelweis University

Budapest, 1082, Hungary

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia

Budapest, H-1032, Hungary

Location

Cork University Hospital

Cork, Ireland

Location

Sieff Hospital

Safed, 13110, Israel

Location

Ospedale San Lazzaro

Alba, 12051, Italy

Location

Ospedale Presenti Fenaroli

Alzano Lombardo, 24022, Italy

Location

Centro di Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

Ospedali Riuniti di Bergamo

Bergamo, 24100, Italy

Location

Ospedale degli Infermi - ASL 12

Biella, 13900, Italy

Location

Ospedale Bellaria

Bologna, I-40139, Italy

Location

Spedali Civili di Brescia

Brescia, 25124, Italy

Location

Ospedale Oncologico A. Businco

Cagliari, 09100, Italy

Location

Ospedale B. Ramazzini

Carpi, 41012, Italy

Location

Ospedale Valduce

Como, 22100, Italy

Location

Ospedale Santa Croce

Cuneo, 12100, Italy

Location

Universita Degli Studi Di Florence

Firenze (Florence), 50121, Italy

Location

Azienda Ospedaliero Careggi

Florence, 50139, Italy

Location

Morgagni-Pierantoni Ospedale

Forlì, 47100, Italy

Location

Istituto Nazionale per la Ricerca sul Cancro

Genoa, 16132, Italy

Location

Ospedale A. Manzoni

Lecco, 23900, Italy

Location

Presidio Ospedaliero

Livorno, 57100, Italy

Location

Carlo Poma Hospital

Mantova, 46100, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Ospedale Niguarda Ca'Granda

Milan, 20162, Italy

Location

University of Modena Hospital and Reggio Emilia School of Medicine

Modena, 41100, Italy

Location

Azienda Ospedaliera Di Parma

Parma, 43100, Italy

Location

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

Pavia, 27100, Italy

Location

Policlinico Monteluce

Perugia, 06122, Italy

Location

Azienda Ospedaliera

Reggio Emilia, 42100, Italy

Location

Ospedale San Filippo Neri

Rome, 00135, Italy

Location

Ospedale Sant' Eugenio

Rome, 00144, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Ospedale Civile ASL 1

Sassari, 07100, Italy

Location

Primario U.O. di Oncologia Medica

Trento, 38100, Italy

Location

Ospedale Ostetrico Ginecologica Sant Anna

Turin, 10126, Italy

Location

Universita di Torino

Turin, 10126, Italy

Location

Tokai University School Of Medicine

Kanagawa, 259-1193, Japan

Location

Tokyo Metropolitan - Komagome Hospital

Tokyo, 113-8677, Japan

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6202 AZ, Netherlands

Location

Maasland Hospital

Sittard, 6131 BK, Netherlands

Location

Diakonessenhuis Utrecht

Utrecht, 3508 TG, Netherlands

Location

Medical University of Gdansk

Gdansk, 80-211, Poland

Location

Oncologic Center

Gliwice, 44-101, Poland

Location

Medical University

Poznan, 61-878, Poland

Location

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, 02-781, Poland

Location

Instituto Portugues de Oncologia, Centro Regional de Coimbra

Coimbra, 3000-075, Portugal

Location

Hospitais da Universidade de Coimbra (HUC)

Coimbra, 3000, Portugal

Location

Maternidade Byssaia Barreto

Coimbra, 3000, Portugal

Location

Hospital Distrital De Faro

Faro, 8000, Portugal

Location

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

Lisbon, 1099-023 Codex, Portugal

Location

University Hospital of Santa Maria

Lisbon, 1649-035, Portugal

Location

Moscow Oncology Hospital

Moscow, 107005, Russia

Location

P.A. Hertzen Research Oncology Institute

Moscow, 125284, Russia

Location

Johns Hopkins Singapore International Medical Centre

Singapore, 308433, Singapore

Location

Groote Schuur Hospital

Cape Town, 7925, South Africa

Location

Parklands Hospital

Durban, 4001, South Africa

Location

Sandton Oncology Centre

Johannesburg, 2121, South Africa

Location

Medical Oncology Centre of Rosebank

Johannesburg, 2193, South Africa

Location

Pretoria - East Hospital

Lynnwood, 0081, South Africa

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Yonsei Cancer Center at Yonsei University Medical Center

Seoul, 120-752, South Korea

Location

Centro Oncologico De Galicia Jose Antonio Quirogay Pineyro

A Coruña, 15009, Spain

Location

Hospital De La Ribera

Alzira, 46600, Spain

Location

Hospital Del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario San Cecilio de Granada

Granada, 18003, Spain

Location

Hospital General Universitario De Guadalajara

Guadalajara, 19002, Spain

Location

Hospital Juan Ramon Jimenez

Huelva, 21005, Spain

Location

Hospital Cuidad de Jaen

Jaén, 23007, Spain

Location

Hospital Insular de Gran Canaria

Las Palmas, G.C., Spain

Location

Hospital de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, 35020, Spain

Location

Hospital de la Princesa

Madrid, 28006, Spain

Location

Complejo Hospitalario Santa Maria

Ourense, 32005, Spain

Location

Complejo Hospitalario de Pontevedra

Pontevedra, 36001, Spain

Location

Consorci Hospitalari del Parc Tauli

Sabadell, 08208, Spain

Location

Hospital Universitario Canarias

San Cristóbal de La Laguna, 38320, Spain

Location

Hospital Universitario Nuestra Senora de la Candelaria

Santa Cruz de Tenerife, 38010, Spain

Location

Hospital Universidad Virgen Del Rocio

Seville, E- 41013, Spain

Location

Hospital Virgen Del La Salud

Toledo, 45004, Spain

Location

Hospital General Universitario Valencia

Valencia, 41014, Spain

Location

Complexo Hospitalario Xeral de Vigo

Vigo Pontevedra, 36204, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 59009, Spain

Location

University Hospital of Linkoping

Linköping, S-581 85, Sweden

Location

University Hospital of Malmoe

Malmo, 20502, Sweden

Location

Sahlgrenska University Hospital - Molndal at Gothenburg University

Mölndal, S-43180, Sweden

Location

Karolinska University Hospital - Huddinge

Stockholm, S-171 76, Sweden

Location

Umea Universitet

Umeå, SE-901 87, Sweden

Location

Uppsala University Hospital

Uppsala, SE-75185, Sweden

Location

Kantonspital Aarau

Aarau, 5001, Switzerland

Location

Universitaetsspital-Basel

Basel, CH-4031, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Spitaeler Chur AG

Chur, CH-7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Ospedale Beata Vergine

Mendrisio, CH-6850, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Chulalongkorn University Hospital

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Bradford Hospitals NHS Trust

Bradford, England, BD9 6RJ, United Kingdom

Location

Broomfield Hospital

Chelmsford, Essex, England, CM1 7ET, United Kingdom

Location

Saint Margaret's Hospital

Epping Essex, England, CM16 6TN, United Kingdom

Location

Diana Princess of Wales Hospital

Grimsby, England, DN33 2BA, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, HD3 3EA, United Kingdom

Location

Princess Royal Hospital

Hull, England, HU8 9HE, United Kingdom

Location

Cookridge Hospital at Leeds Teaching Hospital NHS Trust

Leeds, England, LS16 6QB, United Kingdom

Location

Imperial College of Medicine

London, England, W12 0NN, United Kingdom

Location

James Cook University Hospital

Middlesbrough, England, TS4 3BW, United Kingdom

Location

Northern Centre for Cancer Treatment at Newcastle General Hospital

Newcastle upon Tyne, England, NE4 6BE, United Kingdom

Location

Cancer Research Centre at Weston Park Hospital

Sheffield, England, S1O 2SJ, United Kingdom

Location

Airedale General Hospital

West Yorkshire, England, BD20 6TD, United Kingdom

Location

Southend NHS Trust Hospital

Westcliff-on-Sea, England, SS0 0RY, United Kingdom

Location

Related Publications (19)

• Jahanzeb M. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008 Aug;8(4):324-33. doi: 10.3816/CBC.2008.n.037.

  PMID: 18757259 BACKGROUND

• Shiroiwa T, Fukuda T, Shimozuma K, Ohashi Y, Tsutani K. The model-based cost-effectiveness analysis of 1-year adjuvant trastuzumab treatment: based on 2-year follow-up HERA trial data. Breast Cancer Res Treat. 2008 Jun;109(3):559-66. doi: 10.1007/s10549-007-9679-4. Epub 2007 Jul 28.

  PMID: 17661170 BACKGROUND

• Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R; Herceptin Adjuvant (HERA) Trial Study Team. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011 Mar;12(3):236-44. doi: 10.1016/S1470-2045(11)70033-X. Epub 2011 Feb 25.

  PMID: 21354370 RESULT

• Procter M, Suter TM, de Azambuja E, Dafni U, van Dooren V, Muehlbauer S, Climent MA, Rechberger E, Liu WT, Toi M, Coombes RC, Dodwell D, Pagani O, Madrid J, Hall M, Chen SC, Focan C, Muschol M, van Veldhuisen DJ, Piccart-Gebhart MJ. Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin Adjuvant (HERA) trial. J Clin Oncol. 2010 Jul 20;28(21):3422-8. doi: 10.1200/JCO.2009.26.0463. Epub 2010 Jun 7.

  PMID: 20530280 RESULT

• Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U, Rueschoff J, Jordan B, Dolci S, Abramovitz M, Stoss O, Viale G, Gelber RD, Piccart-Gebhart M, Leyland-Jones B. Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol. 2009 Jun 20;27(18):2962-9. doi: 10.1200/JCO.2008.19.7939. Epub 2009 Apr 13.

  PMID: 19364966 RESULT

• Untch M, Gelber RD, Jackisch C, Procter M, Baselga J, Bell R, Cameron D, Bari M, Smith I, Leyland-Jones B, de Azambuja E, Wermuth P, Khasanov R, Feng-Yi F, Constantin C, Mayordomo JI, Su CH, Yu SY, Lluch A, Senkus-Konefka E, Price C, Haslbauer F, Suarez Sahui T, Srimuninnimit V, Colleoni M, Coates AS, Piccart-Gebhart MJ, Goldhirsch A; HERA Study Team. Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol. 2008 Jun;19(6):1090-6. doi: 10.1093/annonc/mdn005. Epub 2008 Feb 21.

  PMID: 18296421 RESULT

• McCaskill-Stevens W, Procter M, Goodbrand J, et al.: Disease-free survival according to local immunohistochemistry for HER2 and central fluorescence in situ hydridization for patients treated with adjuvant chemotherapy with and without trastuzumab in the HERA (BIG 01-01) trial. [Abstract] Breast Cancer Res Treat 106 (1): A-71, S18, 2007.

  RESULT

• Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sanchez Rovira P, Piccart-Gebhart MJ; HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36. doi: 10.1016/S0140-6736(07)60028-2.

  PMID: 17208639 RESULT

• Suter TM, Procter M, van Veldhuisen DJ, Muscholl M, Bergh J, Carlomagno C, Perren T, Passalacqua R, Bighin C, Klijn JG, Ageev FT, Hitre E, Groetz J, Iwata H, Knap M, Gnant M, Muehlbauer S, Spence A, Gelber RD, Piccart-Gebhart MJ. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol. 2007 Sep 1;25(25):3859-65. doi: 10.1200/JCO.2006.09.1611. Epub 2007 Jul 23.

  PMID: 17646669 RESULT

• Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. doi: 10.1056/NEJMoa052306.

  PMID: 16236737 RESULT

• Bae SJ, Moon S, Kook Y, Baek SH, Lee M, Kim JH, Ahn SG, Jeong J. Clinical relevance of clinical treatment score post-5 years (CTS5) in HR-positive, HER2-positive breast cancer. NPJ Breast Cancer. 2025 Apr 2;11(1):33. doi: 10.1038/s41523-025-00747-6.

  PMID: 40175431 DERIVED

• Yerushalmi R, Dong B, Chapman JW, Goss PE, Pollak MN, Burnell MJ, Levine MN, Bramwell VHC, Pritchard KI, Whelan TJ, Ingle JN, Shepherd LE, Parulekar WR, Han L, Ding K, Gelmon KA. Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials. Ann Oncol. 2017 Jul 1;28(7):1560-1568. doi: 10.1093/annonc/mdx152.

  PMID: 28379421 DERIVED

• Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C; Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205. doi: 10.1016/S0140-6736(16)32616-2. Epub 2017 Feb 17.

  PMID: 28215665 DERIVED

• Loi S, Dafni U, Karlis D, Polydoropoulou V, Young BM, Willis S, Long B, de Azambuja E, Sotiriou C, Viale G, Ruschoff J, Piccart MJ, Dowsett M, Michiels S, Leyland-Jones B. Effects of Estrogen Receptor and Human Epidermal Growth Factor Receptor-2 Levels on the Efficacy of Trastuzumab: A Secondary Analysis of the HERA Trial. JAMA Oncol. 2016 Aug 1;2(8):1040-7. doi: 10.1001/jamaoncol.2016.0339.

  PMID: 27100299 DERIVED

• O'Sullivan CC, Bradbury I, Campbell C, Spielmann M, Perez EA, Joensuu H, Costantino JP, Delaloge S, Rastogi P, Zardavas D, Ballman KV, Holmes E, de Azambuja E, Piccart-Gebhart M, Zujewski JA, Gelber RD. Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer and Tumors </= 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials. J Clin Oncol. 2015 Aug 20;33(24):2600-8. doi: 10.1200/JCO.2015.60.8620. Epub 2015 Jun 22.

  PMID: 26101239 DERIVED

• de Azambuja E, Procter MJ, van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J, Untch M, Smith IE, Gianni L, Baselga J, Jackisch C, Cameron DA, Bell R, Leyland-Jones B, Dowsett M, Gelber RD, Piccart-Gebhart MJ, Suter TM. Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01). J Clin Oncol. 2014 Jul 10;32(20):2159-65. doi: 10.1200/JCO.2013.53.9288. Epub 2014 Jun 9.

  PMID: 24912899 DERIVED

• Zabaglo L, Stoss O, Ruschoff J, Zielinski D, Salter J, Arfi M, Bradbury I, Dafni U, Piccart-Gebhart M, Procter M, Dowsett M; HERA Trial Study Team. HER2 staining intensity in HER2-positive disease: relationship with FISH amplification and clinical outcome in the HERA trial of adjuvant trastuzumab. Ann Oncol. 2013 Nov;24(11):2761-6. doi: 10.1093/annonc/mdt275. Epub 2013 Jul 25.

  PMID: 23894039 DERIVED

• Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Kohne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. doi: 10.1016/S0140-6736(13)61094-6. Epub 2013 Jul 18.

  PMID: 23871490 DERIVED

• Metzger-Filho O, Procter M, de Azambuja E, Leyland-Jones B, Gelber RD, Dowsett M, Loi S, Saini KS, Cameron D, Untch M, Smith I, Gianni L, Baselga J, Jackisch C, Bell R, Sotiriou C, Viale G, Piccart-Gebhart M. Magnitude of trastuzumab benefit in patients with HER2-positive, invasive lobular breast carcinoma: results from the HERA trial. J Clin Oncol. 2013 Jun 1;31(16):1954-60. doi: 10.1200/JCO.2012.46.2440. Epub 2013 Apr 15.

  PMID: 23589556 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

global-roche-genentech-trials@gene.com

800-821-8590

Study Officials

• Martine J. Piccart-Gebhart, MD, PhD

  Jules Bordet Institute

  STUDY CHAIR

• Robert E. Coleman, MD, FRCP

  Cancer Research Centre at Weston Park Hospital

  STUDY CHAIR

• Karen A. Gelmon, MD

  British Columbia Cancer Agency

  STUDY CHAIR

• Kathleen I. Pritchard, MD

  Toronto Sunnybrook Regional Cancer Centre

  STUDY CHAIR

• Olivia Pagani, MD

  Ospedale Beata Vergine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2002
• First Posted: January 27, 2003
• Study Start: November 1, 2001
• Primary Completion: March 1, 2005
• Study Completion: June 1, 2015
• Last Updated: April 27, 2017
• Results First Posted: April 27, 2017

Record last verified: 2017-03

Locations

HK (1); CL (5); AU (4); CR (1); AR (1); RU (2); TH (2); NL (3); PT (6); PL (4); ES (20); GR (2); HU (3); SE (6); CA (19); IE (1); JP (2); GU (2); KR (2); IT (32); BE (14); IL (1); DK (5); CN (3); FR (3); SG (1); CH (8); ZA (5); DE (15); BR (5); CO (1); GB (13)