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

This study has been completed.
Sponsor:
Collaborators:
Breast International Group
European Organisation for Research and Treatment of Cancer - EORTC
NCIC Clinical Trials Group
International Breast Cancer Study Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00045032
First received: September 6, 2002
Last updated: March 17, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Breast Cancer Drug: Herceptin Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized Three-Arm, Multicenter Comparison of 1 Year and 2 Years of Herceptin Versus No Herceptin in Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
    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.

  • Percentage of Participants With DFS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
    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.

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

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

  • Percentage of Participants With DFS Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    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.

  • DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 3 ]
    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.

  • DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 5 ]
    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.

  • DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 7 ]
    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.

  • DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Year 8 ]
    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.

  • Percentage of Participants With DFS Events Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum of 10 years) ]
    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.

  • DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 3 ]
    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.

  • DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 5 ]
    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.

  • DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 7 ]
    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.

  • DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 8 ]
    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.

  • DFS Rate at Year 9 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 9 ]
    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.

  • DFS Rate at Year 10 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: Year 10 ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With DFS Events in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum of 10 years) ]
    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.

  • DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up [ Time Frame: Years 3, 5, 7, 8, 9, 10 ]
    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.

  • Percentage of Participants With Overall Survival (OS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
    OS events referred to death from any cause. The percentage of participants who died 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 IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

  • Percentage of Participants With OS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 1 year) ]
    OS events referred to death from any cause. The percentage of participants who died 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.

  • OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: Year 2 ]
    OS events referred to death from any cause. The percentage of participants alive (i.e., the OS 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 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.

  • OS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up [ Time Frame: Year 2 ]
    OS events referred to death from any cause. The percentage of participants alive (i.e., the OS 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.

  • Percentage of Participants With OS Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    OS events referred to death from any cause. The percentage of participants who died was reported.

  • OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    OS events referred to death from any cause. The percentage of participants alive (i.e., the OS 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.

  • Percentage of Participants With OS Events Compared to Observation: 11-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 11 years) ]
    OS events referred to death from any cause. The percentage of participants who died was reported.

  • OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 9, 10, 11, 12 ]
    OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.

  • Percentage of Participants With OS Events in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 11 years) ]
    OS events referred to death from any cause. The percentage of participants who died was reported.

  • OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 9, 10, 11, 12 ]
    OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.

  • Percentage of Participants With Recurrence-Free Survival (RFS) Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.

  • RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS 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.

  • Percentage of Participants With RFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.

  • RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS 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.

  • Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.

  • DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS 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.

  • Percentage of Participants With DDFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.

  • DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS 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.

  • Percentage of Participants With Tumor Recurrence (TR) Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

  • TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without TR of the present breast cancer (i.e., the TR-free 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. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

  • Percentage of Participants With TR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

  • TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without TR of the present breast cancer (i.e., the TR-free 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. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

  • Percentage of Participants With Distant Tumor Recurrence (DTR) Compared to Observation: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

  • DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without DTR (i.e., the DTR-free 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. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

  • Percentage of Participants With DTR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

  • DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    The percentage of participants without DTR (i.e., the DTR-free 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. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

  • Percentage of Participants With Restricted Disease-Free Survival (RDFS) Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: From Baseline until time of event (median of 8 years) ]
    RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants with at least one RDFS event was reported.

  • RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up [ Time Frame: Years 3, 5, 7, 8 ]
    RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants free of RDFS events (i.e., the RDFS 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.

  • Percentage of Participants With Primary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum up to 10 years) ]
    Primary cardiac endpoint events included the occurrence of any of the following between randomization and new therapy for recurrent disease: symptomatic New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) confirmed by a cardiologist with a drop in left ventricular ejection fraction (LVEF) at least 10 percentage points from Baseline and to a value less than (<) 50%, and documentation of definite or probable cardiac death. Definite cardiac death included CHF, myocardial infarction, or primary arrhythmia. Probable cardiac death included unexpected sudden death within 24 hours of a cardiac event (syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology. The percentage of participants with at least one primary cardiac endpoint event was reported. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.

  • Percentage of Participants With Secondary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up [ Time Frame: From Baseline until time of event (maximum up to 10 years) ]
    Secondary cardiac endpoint events included NYHA Class I or II CHF with a drop in LVEF measured by multiple-gated acquisition or electrocardiogram, unless the subsequent assessment of LVEF indicated a return to levels that did not meet the definition of a significant LVEF drop. A significant LVEF drop was defined as an absolute reduction of at least 10 percentage points from Baseline and to a value <50%. The percentage of participants with at least one secondary cardiac endpoint event was reported, excluding those with both a primary and secondary cardiac endpoint event. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.


Enrollment: 5099
Study Start Date: November 2001
Study Completion Date: June 2015
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 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.
Experimental: 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.
Drug: 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.
Other Name: Trastuzumab
Experimental: 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.
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.
Other Name: Trastuzumab

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045032

  Hide Study Locations
Locations
Argentina
Hospital Aleman de Buenos Aires
Buenos Aires, Argentina, 1118
Australia, Australian Capital Territory
Saint John of God Hospital
Geelong, Australian Capital Territory, Australia, 3220
Australia, Queensland
Toowoomba Hospital
Toowoomba, Queensland, Australia, 4350
Australia, Victoria
Andrew Love Cancer Centre
Geelong, Victoria, Australia, 3220
Australia, Western Australia
Mount Hospital
Perth, Western Australia, Australia, 6000
Austria
Landeskrankenhaus Feldkirch
Feldkirch-Tisis, Austria, 6807
Innsbruck Universitaetsklinik
Innsbruck, Austria, A-6020
Landeskrankenhaus Klagenfurt
Klagenfurt, Austria, 9026
St. Vincent's Hospital
Linz Donau, Austria, A-4010
Landeskrankenanstalten - Salzburg
Salzburg, Austria, A-5020
Landeskrankenhaus St. Poelten
St. Poelten, Austria, 3100
Universitaetsklinik fuer Innere Medizin I
Vienna, Austria, 1090
Wilhelminenspital der Stadt Wien
Vienna, Austria, A-1160
LKH Villach
Villach, Austria, 9500
LKH Voecklabruck
Voecklabruck, Austria, 4840
A. oe. Krankenhaus Wiener Neustadt
Wiener Neustadt, Austria, A-2700
Belgium
Ziekenhuis Netwerk Antwerpen Middelheim
Antwerp, Belgium, 2020
Reseau Hospitalier De Medecine Sociale
Baudour, Belgium, 7331
Hopital Universitaire Erasme
Brussels, Belgium, 1070
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, Belgium, 1090
Institut Jules Bordet
Brussels, Belgium, B-1000
Centre Hospitalier Notre Dame - Reine Fabiola
Charleroi, Belgium, 6000
Cazk Groeninghe - Campus St-Niklaas
Kortrijk, Belgium, B-8500
Centre Hospitalier Universitaire de Tivoli
La Louviere, Belgium, 7100
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Clinique Saint-Joseph
Liege, Belgium, B 4000
CHU Liege - Domaine Universitaire du Sart Tilman
Liege, Belgium, B-4000
Clinique Sainte Elisabeth
Namur, Belgium, 5000
Hospital Serruys Ziekenhuis
Oostende, Belgium, 8400
Centre Hospitalier Peltzer-La Tourelle
Verviers, Belgium, B-4800
Brazil
Porto Alegre Hospital
Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
Hospital Sao Lucas da PUCRS
Porto Alegre, Brazil, 90610-000
Hospital Santa Rita
Porto Alegre, Brazil, 91330-490
Instituto Nacional de Cancer
Rio de Janeiro, Brazil, 20560-120
Faculdade De Medicina Do ABC
Santo Andre, Brazil, 09060-650
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
British Columbia Cancer Agency - Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
Fraser Valley Cancer Centre at British Columbia Cancer Agency
Surrey, British Columbia, Canada, V3V 1Z2
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
British Columbia Cancer Agency - Vancouver Island Cancer Centre
Victoria, British Columbia, Canada, V8R 6V5
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, Ontario
Royal Victoria Hospital of Barrie
Barrie, Ontario, Canada, L4M 6M2
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Trillium Health Centre - Mississauga Site
Mississauga, Ontario, Canada, L5B 1B8
Algoma Regional Cancer Program at Sault Area Hospital
Sault Sainte Marie, Ontario, Canada, P6A 2C4
Hotel Dieu Health Sciences Hospital - Niagara
St. Catharines, Ontario, Canada, L2R 5K3
Toronto East General Hospital
Toronto, Ontario, Canada, M4C 3E7
Mount Sinai Hospital - Toronto
Toronto, Ontario, Canada, M5G 1X5
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Windsor Regional Cancer Centre at Windsor Regional Hospital
Windsor, Ontario, Canada, N8W 2X3
Canada, Prince Edward Island
Prince Edward Island Cancer Centre at Queen Elizabeth Hospital
Charlottetown, Prince Edward Island, Canada, C1A 8T5
Canada, Quebec
Hopital du Saint-Sacrement, Quebec
Quebec City, Quebec, Canada, G1S 4L8
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Chile
Fundacion Arturo Lopez Perez
Santiago, Chile, 29
Hospital Clinico San Borja Arriaran
Santiago, Chile
Hospital Dr. Sotero Del Rio
Santiago, Chile
Hospital Militar
Santiago, Chile
Instituto Nacional Del Cancer
Santiago, Chile
China
Queen Mary Hospital
Hong Kong, China
Tuen Mun Hospital
Hong Kong, China
Tongji Medical University
Wuhan, China, 430030
Colombia
Instituto Nacional De Cancerologia
Bogota, Colombia
Croatia
Clinical Hospital Center Split
Split, Croatia, 21000
Denmark
Centralsygehus I Esbjerg
Esbjerg, Denmark, 6700
Herning Central Hospital
Herning, Denmark, 7400
Hillerod Hospital
Hillerod, Denmark, 3400
Centralsygehuset I Naestved
Naestved, Denmark, 4700
Sonderborg Sygehus
Sonderborg, Denmark, 6400
France
Centre Regional Francois Baclesse
Caen, France, 14076
Centre Hospital Regional Universitaire de Limoges
Limoges, France, 87042
Hopital Clinique Claude Bernard
Metz, France, 57072
Germany
Charite - Campus Charite Mitte
Berlin, Germany, D-10117
Evangelisches Bethesda Krankenhaus GmbH
Essen, Germany, D-45355
Universitaetsklinikum Freiburg
Freiburg, Germany, D-79106
Martin Luther Universitaet
Halle, Germany, D-06097
Henriettenstiftung Krankenhaus
Hanover, Germany, D-30559
Universitaets-Hautklinik Heidelberg
Heidelberg, Germany, D-69115
St. Vincentius-Kliniken
Karlsruhe, Germany, D-76137
University Hospital Schleswig-Holstein - Kiel Campus
Kiel, Germany, D-24105
Kreiskrankenhaus Leonberg - Frauenklinik
Leonberg, Germany, D-71229
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
Magdeburg, Germany, D-39120
Frauenklinik Vom Roten Kreuz
Munich, Germany, 80637
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany, D-81675
Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt
Rostock, Germany, D-18059
Universitaet Ulm
Ulm, Germany, D-89075
Dr. Horst-Schmidt-Kliniken
Wiesbaden, Germany, D-65199
Greece
University of Crete School of Medicine
Heraklion, Crete, Greece, 71110
Evaggelismos Hospital
Athens, Greece, 10676
Guatemala
Centro Medico
Guatemala City, Guatemala, 01010
Hospital Roosevelt
Guatemala City, Guatemala, 01010
Hong Kong
Prince of Wales Hospital
Shatin, New Territories, Hong Kong
Hungary
Semmelweis University
Budapest, Hungary, 1082
National Institute of Oncology
Budapest, Hungary, 1122
Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia
Budapest, Hungary, H-1032
Ireland
Cork University Hospital
Cork, Ireland
Israel
Sieff Hospital
Safed, Israel, 13110
Italy
Ospedale San Lazzaro
Alba, Italy, 12051
Ospedale Presenti Fenaroli
Alzano-Lombardo, Italy, 24022
Centro di Riferimento Oncologico - Aviano
Aviano, Italy, 33081
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24100
Ospedale degli Infermi - ASL 12
Biella, Italy, 13900
Ospedale Bellaria
Bologna, Italy, I-40139
Spedali Civili di Brescia
Brescia, Italy, 25124
Ospedale Oncologico A. Businco
Cagliari, Italy, 09100
Ospedale B. Ramazzini
Carpi, Italy, 41012
Ospedale Valduce
Como, Italy, 22100
Ospedale Santa Croce
Cuneo, Italy, 12100
Universita Degli Studi Di Florence
Firenze (Florence), Italy, 50121
Azienda Ospedaliero Careggi
Florence, Italy, 50139
Morgagni-Pierantoni Ospedale
Forli, Italy, 47100
Istituto Nazionale per la Ricerca sul Cancro
Genoa, Italy, 16132
Ospedale A. Manzoni
Lecco, Italy, 23900
Presidio Ospedaliero
Livorno, Italy, 57100
Carlo Poma Hospital
Mantova, Italy, 46100
European Institute of Oncology
Milan, Italy, 20141
Ospedale Niguarda Ca'Granda
Milan, Italy, 20162
University of Modena Hospital and Reggio Emilia School of Medicine
Modena, Italy, 41100
Azienda Ospedaliera Di Parma
Parma, Italy, 43100
I.R.C.C.S. Policlinico San Matteo
Pavia, Italy, 27100
Policlinico Monteluce
Perugia, Italy, 06122
Azienda Ospedaliera
Reggio Emilia, Italy, 42100
Ospedale San Filippo Neri
Rome, Italy, 00135
Ospedale Sant' Eugenio
Rome, Italy, 00144
Istituto Clinico Humanitas
Rozzano, Italy, 20089
Ospedale Civile ASL 1
Sassari, Italy, 07100
Primario U.O. di Oncologia Medica
Trento, Italy, 38100
Ospedale Ostetrico Ginecologica Sant Anna
Turin, Italy, 10126
Universita di Torino
Turin, Italy, 10126
Japan
Tokai University School Of Medicine
Kanagawa, Japan, 259-1193
Tokyo Metropolitan - Komagome Hospital
Tokyo, Japan, 113-8677
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Yonsei Cancer Center at Yonsei University Medical Center
Seoul, Korea, Republic of, 120-752
Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6202 AZ
Maasland Hospital
Sittard, Netherlands, 6131 BK
Diakonessenhuis Utrecht
Utrecht, Netherlands, 3508 TG
Poland
Medical University of Gdansk
Gdansk, Poland, 80-211
Oncologic Center
Gliwice, Poland, 44-101
Medical University
Poznan, Poland, 61-878
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Warsaw, Poland, 02-781
Portugal
Instituto Portugues de Oncologia, Centro Regional de Coimbra
Coimbra, Portugal, 3000-075
Hospitais da Universidade de Coimbra (HUC)
Coimbra, Portugal, 3000
Maternidade Byssaia Barreto
Coimbra, Portugal, 3000
Hospital Distrital De Faro
Faro, Portugal, 8000
University Hospital of Santa Maria
Lisboa, Portugal, 1649-035
Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.
Lisbon, Portugal, 1099-023 Codex
Russian Federation
Moscow Oncology Hospital
Moscow, Russian Federation, 107005
P.A. Hertzen Research Oncology Institute
Moscow, Russian Federation, 125284
Singapore
Johns Hopkins Singapore International Medical Centre
Singapore, Singapore, 308433
South Africa
Groote Schuur Hospital
Cape Town, South Africa, 7925
Parklands Hospital
Durban, South Africa, 4001
Sandton Oncology Centre
Johannesburg, South Africa, 2121
Medical Oncology Centre of Rosebank
Johannesburg, South Africa, 2193
Pretoria - East Hospital
Lynnwood, South Africa, 0081
Spain
Hospital De La Ribera
Alzira, Spain, 46600
Hospital Del Mar
Barcelona, Spain, 08003
Hospital Universitario San Cecilio de Granada
Granada, Spain, 18003
Hospital General Universitario De Guadalajara
Guadalajara, Spain, 19002
Hospital Juan Ramon Jimenez
Huelva, Spain, 21005
Hospital Cuidad de Jaen
Jaen, Spain, 23007
Centro Oncologico De Galicia Jose Antonio Quirogay Pineyro
La Coruna, Spain, 15009
Hospital Universitario Canarias
La Laguna, Spain, 38320
Hospital de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria, Spain, 35020
Hospital Insular de Gran Canaria
Las Palmas, Spain, G.C.
Hospital de la Princesa
Madrid, Spain, 28006
Complejo Hospitalario Santa Maria
Orense, Spain, 32005
Complejo Hospitalario de Pontevedra
Pontevedra, Spain, 36001
Consorci Hospitalari del Parc Tauli
Sabadell, Spain, 08208
Hospital Universitario Nuestra Senora de la Candelaria
Santa Cruz de Tenerife, Spain, 38010
Hospital Universidad Virgen Del Rocio
Sevilla, Spain, E- 41013
Hospital Virgen Del La Salud
Toledo, Spain, 45004
Hospital General Universitario Valencia
Valencia, Spain, 41014
Complexo Hospitalario Xeral de Vigo
Vigo Pontevedra, Spain, 36204
Hospital Universitario Miguel Servet
Zaragoza, Spain, 59009
Sweden
University Hospital of Linkoping
Linkoping, Sweden, S-581 85
University Hospital of Malmoe
Malmo, Sweden, 20502
Sahlgrenska University Hospital - Molndal at Gothenburg University
Molndal, Sweden, S-43180
Karolinska University Hospital - Huddinge
Stockholm, Sweden, S-171 76
Umea Universitet
Umea, Sweden, SE-901 87
Uppsala University Hospital
Uppsala, Sweden, SE-75185
Switzerland
Kantonspital Aarau
Aarau, Switzerland, 5001
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Inselspital Bern
Bern, Switzerland, CH-3010
Spitaeler Chur AG
Chur, Switzerland, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Ospedale Beata Vergine
Mendrisio, Switzerland, CH-6850
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Thailand
Chulalongkorn University Hospital
Bangkok, Thailand, 10330
Ramathibodi Hospital
Bangkok, Thailand, 10400
United Kingdom
Bradford Hospitals NHS Trust
Bradford, England, United Kingdom, BD9 6RJ
Broomfield Hospital
Chelmsford, Essex, England, United Kingdom, CM1 7ET
Saint Margaret's Hospital
Epping Essex, England, United Kingdom, CM16 6TN
Diana Princess of Wales Hospital
Grimsby, England, United Kingdom, DN33 2BA
Huddersfield Royal Infirmary
Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
Princess Royal Hospital
Hull, England, United Kingdom, HU8 9HE
Cookridge Hospital at Leeds Teaching Hospital NHS Trust
Leeds, England, United Kingdom, LS16 6QB
Imperial College of Medicine
London, England, United Kingdom, W12 0NN
James Cook University Hospital
Middlesbrough, England, United Kingdom, TS4 3BW
Northern Centre for Cancer Treatment at Newcastle General Hospital
Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
Cancer Research Centre at Weston Park Hospital
Sheffield, England, United Kingdom, S1O 2SJ
Airedale General Hospital
West Yorkshire, England, United Kingdom, BD20 6TD
Southend NHS Trust Hospital
Westcliff-On-Sea, England, United Kingdom, SS0 0RY
Sponsors and Collaborators
Hoffmann-La Roche
Breast International Group
European Organisation for Research and Treatment of Cancer - EORTC
NCIC Clinical Trials Group
International Breast Cancer Study Group
Investigators
Study Chair: 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
  More Information

Publications:
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00045032     History of Changes
Other Study ID Numbers: BO16348
BIG-01-01
EU-20216
ROCHE-B016348E
ROCHE-B016348C
EORTC-10011
CAN-NCIC-MA24
IBCSG-28-02
Study First Received: September 6, 2002
Results First Received: October 19, 2016
Last Updated: March 17, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 19, 2017