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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00045032




Registration number
NCT00045032
Ethics application status
Date submitted
6/09/2002
Date registered
27/01/2003
Date last updated
27/04/2017

Titles & IDs
Public title
Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer
Scientific 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
Secondary ID [1] 0 0
BIG-01-01
Secondary ID [2] 0 0
BO16348
Universal Trial Number (UTN)
Trial acronym
HERA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Herceptin
Treatment: Drugs - Herceptin

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
From Baseline until time of event (median of 1 year)
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
From Baseline until time of event (median of 1 year)
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
Year 2
Primary outcome [4] 0 0
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.
Timepoint [4] 0 0
Year 2
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
From Baseline until time of event (median of 8 years)
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
Year 3
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
Year 5
Primary outcome [8] 0 0
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.
Timepoint [8] 0 0
Year 7
Primary outcome [9] 0 0
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.
Timepoint [9] 0 0
Year 8
Primary outcome [10] 0 0
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.
Timepoint [10] 0 0
From Baseline until time of event (maximum of 10 years)
Primary outcome [11] 0 0
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.
Timepoint [11] 0 0
Year 3
Primary outcome [12] 0 0
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.
Timepoint [12] 0 0
Year 5
Primary outcome [13] 0 0
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.
Timepoint [13] 0 0
Year 7
Primary outcome [14] 0 0
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.
Timepoint [14] 0 0
Year 8
Primary outcome [15] 0 0
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.
Timepoint [15] 0 0
Year 9
Primary outcome [16] 0 0
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.
Timepoint [16] 0 0
Year 10
Secondary outcome [1] 0 0
Percentage of Participants With DFS Events in 1-Year Versus 2-Year Herceptin: 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.
Timepoint [1] 0 0
From Baseline until time of event (maximum of 10 years)
Secondary outcome [2] 0 0
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 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.
Timepoint [2] 0 0
Years 3, 5, 7, 8, 9, 10
Secondary outcome [3] 0 0
Percentage of Participants With Overall Survival (OS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up - 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.
Timepoint [3] 0 0
From Baseline until time of event (median of 1 year)
Secondary outcome [4] 0 0
Percentage of Participants With OS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up - 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.
Timepoint [4] 0 0
From Baseline until time of event (median of 1 year)
Secondary outcome [5] 0 0
OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up - 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.
Timepoint [5] 0 0
Year 2
Secondary outcome [6] 0 0
OS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up - 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.
Timepoint [6] 0 0
Year 2
Secondary outcome [7] 0 0
Percentage of Participants With OS Events Compared to Observation: 8-Year Median Follow-Up - OS events referred to death from any cause. The percentage of participants who died was reported.
Timepoint [7] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [8] 0 0
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [8] 0 0
Years 3, 5, 7, 8
Secondary outcome [9] 0 0
Percentage of Participants With OS Events Compared to Observation: 11-Year Median Follow-Up - OS events referred to death from any cause. The percentage of participants who died was reported.
Timepoint [9] 0 0
From Baseline until time of event (median of 11 years)
Secondary outcome [10] 0 0
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up - 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.
Timepoint [10] 0 0
Years 3, 5, 7, 9, 10, 11, 12
Secondary outcome [11] 0 0
Percentage of Participants With OS Events in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up - OS events referred to death from any cause. The percentage of participants who died was reported.
Timepoint [11] 0 0
From Baseline until time of event (median of 11 years)
Secondary outcome [12] 0 0
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up - 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.
Timepoint [12] 0 0
Years 3, 5, 7, 9, 10, 11, 12
Secondary outcome [13] 0 0
Percentage of Participants With Recurrence-Free Survival (RFS) Events Compared to Observation: 8-Year Median Follow-Up - RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.
Timepoint [13] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [14] 0 0
RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [14] 0 0
Years 3, 5, 7, 8
Secondary outcome [15] 0 0
Percentage of Participants With RFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.
Timepoint [15] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [16] 0 0
RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [16] 0 0
Years 3, 5, 7, 8
Secondary outcome [17] 0 0
Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [17] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [18] 0 0
DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [18] 0 0
Years 3, 5, 7, 8
Secondary outcome [19] 0 0
Percentage of Participants With DDFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [19] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [20] 0 0
DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [20] 0 0
Years 3, 5, 7, 8
Secondary outcome [21] 0 0
Percentage of Participants With Tumor Recurrence (TR) Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [21] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [22] 0 0
TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [22] 0 0
Years 3, 5, 7, 8
Secondary outcome [23] 0 0
Percentage of Participants With TR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [23] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [24] 0 0
TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [24] 0 0
Years 3, 5, 7, 8
Secondary outcome [25] 0 0
Percentage of Participants With Distant Tumor Recurrence (DTR) Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [25] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [26] 0 0
DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up - 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.
Timepoint [26] 0 0
Years 3, 5, 7, 8
Secondary outcome [27] 0 0
Percentage of Participants With DTR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [27] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [28] 0 0
DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [28] 0 0
Years 3, 5, 7, 8
Secondary outcome [29] 0 0
Percentage of Participants With Restricted Disease-Free Survival (RDFS) Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [29] 0 0
From Baseline until time of event (median of 8 years)
Secondary outcome [30] 0 0
RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up - 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.
Timepoint [30] 0 0
Years 3, 5, 7, 8
Secondary outcome [31] 0 0
Percentage of Participants With Primary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up - 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.
Timepoint [31] 0 0
From Baseline until time of event (maximum up to 10 years)
Secondary outcome [32] 0 0
Percentage of Participants With Secondary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up - 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.
Timepoint [32] 0 0
From Baseline until time of event (maximum up to 10 years)

Eligibility
Key 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 (%)
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,QLD,VIC,WA
Recruitment hospital [1] 0 0
Saint John of God Hospital - Geelong
Recruitment hospital [2] 0 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [3] 0 0
Andrew Love Cancer Centre - Geelong
Recruitment hospital [4] 0 0
Mount Hospital - Perth
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
4350 - Toowoomba
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Austria
State/province [2] 0 0
Feldkirch-Tisis
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Austria
State/province [3] 0 0
Innsbruck
Country [4] 0 0
Austria
State/province [4] 0 0
Klagenfurt
Country [5] 0 0
Austria
State/province [5] 0 0
Linz Donau
Country [6] 0 0
Austria
State/province [6] 0 0
Salzburg
Country [7] 0 0
Austria
State/province [7] 0 0
St. Poelten
Country [8] 0 0
Austria
State/province [8] 0 0
Vienna
Country [9] 0 0
Austria
State/province [9] 0 0
Villach
Country [10] 0 0
Austria
State/province [10] 0 0
Voecklabruck
Country [11] 0 0
Austria
State/province [11] 0 0
Wiener Neustadt
Country [12] 0 0
Belgium
State/province [12] 0 0
Antwerp
Country [13] 0 0
Belgium
State/province [13] 0 0
Baudour
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussels
Country [15] 0 0
Belgium
State/province [15] 0 0
Charleroi
Country [16] 0 0
Belgium
State/province [16] 0 0
Kortrijk
Country [17] 0 0
Belgium
State/province [17] 0 0
La Louviere
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Belgium
State/province [19] 0 0
Liege
Country [20] 0 0
Belgium
State/province [20] 0 0
Namur
Country [21] 0 0
Belgium
State/province [21] 0 0
Oostende
Country [22] 0 0
Belgium
State/province [22] 0 0
Verviers
Country [23] 0 0
Brazil
State/province [23] 0 0
Rio Grande do Sul
Country [24] 0 0
Brazil
State/province [24] 0 0
Porto Alegre
Country [25] 0 0
Brazil
State/province [25] 0 0
Rio de Janeiro
Country [26] 0 0
Brazil
State/province [26] 0 0
Santo Andre
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia
Country [29] 0 0
Canada
State/province [29] 0 0
Manitoba
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Prince Edward Island
Country [32] 0 0
Canada
State/province [32] 0 0
Quebec
Country [33] 0 0
Canada
State/province [33] 0 0
Saskatchewan
Country [34] 0 0
Chile
State/province [34] 0 0
Santiago
Country [35] 0 0
China
State/province [35] 0 0
Hong Kong
Country [36] 0 0
China
State/province [36] 0 0
Wuhan
Country [37] 0 0
Colombia
State/province [37] 0 0
Bogota
Country [38] 0 0
Croatia
State/province [38] 0 0
Split
Country [39] 0 0
Denmark
State/province [39] 0 0
Esbjerg
Country [40] 0 0
Denmark
State/province [40] 0 0
Herning
Country [41] 0 0
Denmark
State/province [41] 0 0
Hillerod
Country [42] 0 0
Denmark
State/province [42] 0 0
Naestved
Country [43] 0 0
Denmark
State/province [43] 0 0
Sonderborg
Country [44] 0 0
France
State/province [44] 0 0
Caen
Country [45] 0 0
France
State/province [45] 0 0
Limoges
Country [46] 0 0
France
State/province [46] 0 0
Metz
Country [47] 0 0
Germany
State/province [47] 0 0
Berlin
Country [48] 0 0
Germany
State/province [48] 0 0
Essen
Country [49] 0 0
Germany
State/province [49] 0 0
Freiburg
Country [50] 0 0
Germany
State/province [50] 0 0
Halle
Country [51] 0 0
Germany
State/province [51] 0 0
Hanover
Country [52] 0 0
Germany
State/province [52] 0 0
Heidelberg
Country [53] 0 0
Germany
State/province [53] 0 0
Karlsruhe
Country [54] 0 0
Germany
State/province [54] 0 0
Kiel
Country [55] 0 0
Germany
State/province [55] 0 0
Leonberg
Country [56] 0 0
Germany
State/province [56] 0 0
Magdeburg
Country [57] 0 0
Germany
State/province [57] 0 0
Munich
Country [58] 0 0
Germany
State/province [58] 0 0
Rostock
Country [59] 0 0
Germany
State/province [59] 0 0
Ulm
Country [60] 0 0
Germany
State/province [60] 0 0
Wiesbaden
Country [61] 0 0
Greece
State/province [61] 0 0
Crete
Country [62] 0 0
Greece
State/province [62] 0 0
Athens
Country [63] 0 0
Guatemala
State/province [63] 0 0
Guatemala City
Country [64] 0 0
Hong Kong
State/province [64] 0 0
Shatin, New Territories
Country [65] 0 0
Hungary
State/province [65] 0 0
Budapest
Country [66] 0 0
Ireland
State/province [66] 0 0
Cork
Country [67] 0 0
Israel
State/province [67] 0 0
Safed
Country [68] 0 0
Italy
State/province [68] 0 0
Alba
Country [69] 0 0
Italy
State/province [69] 0 0
Alzano-Lombardo
Country [70] 0 0
Italy
State/province [70] 0 0
Aviano
Country [71] 0 0
Italy
State/province [71] 0 0
Bergamo
Country [72] 0 0
Italy
State/province [72] 0 0
Biella
Country [73] 0 0
Italy
State/province [73] 0 0
Bologna
Country [74] 0 0
Italy
State/province [74] 0 0
Brescia
Country [75] 0 0
Italy
State/province [75] 0 0
Cagliari
Country [76] 0 0
Italy
State/province [76] 0 0
Carpi
Country [77] 0 0
Italy
State/province [77] 0 0
Como
Country [78] 0 0
Italy
State/province [78] 0 0
Cuneo
Country [79] 0 0
Italy
State/province [79] 0 0
Firenze (Florence)
Country [80] 0 0
Italy
State/province [80] 0 0
Florence
Country [81] 0 0
Italy
State/province [81] 0 0
Forli
Country [82] 0 0
Italy
State/province [82] 0 0
Genoa
Country [83] 0 0
Italy
State/province [83] 0 0
Lecco
Country [84] 0 0
Italy
State/province [84] 0 0
Livorno
Country [85] 0 0
Italy
State/province [85] 0 0
Mantova
Country [86] 0 0
Italy
State/province [86] 0 0
Milan
Country [87] 0 0
Italy
State/province [87] 0 0
Modena
Country [88] 0 0
Italy
State/province [88] 0 0
Parma
Country [89] 0 0
Italy
State/province [89] 0 0
Pavia
Country [90] 0 0
Italy
State/province [90] 0 0
Perugia
Country [91] 0 0
Italy
State/province [91] 0 0
Reggio Emilia
Country [92] 0 0
Italy
State/province [92] 0 0
Rome
Country [93] 0 0
Italy
State/province [93] 0 0
Rozzano
Country [94] 0 0
Italy
State/province [94] 0 0
Sassari
Country [95] 0 0
Italy
State/province [95] 0 0
Trento
Country [96] 0 0
Italy
State/province [96] 0 0
Turin
Country [97] 0 0
Japan
State/province [97] 0 0
Kanagawa
Country [98] 0 0
Japan
State/province [98] 0 0
Tokyo
Country [99] 0 0
Korea, Republic of
State/province [99] 0 0
Seoul
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Maastricht
Country [101] 0 0
Netherlands
State/province [101] 0 0
Sittard
Country [102] 0 0
Netherlands
State/province [102] 0 0
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Country [103] 0 0
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State/province [103] 0 0
Gdansk
Country [104] 0 0
Poland
State/province [104] 0 0
Gliwice
Country [105] 0 0
Poland
State/province [105] 0 0
Poznan
Country [106] 0 0
Poland
State/province [106] 0 0
Warsaw
Country [107] 0 0
Portugal
State/province [107] 0 0
Coimbra
Country [108] 0 0
Portugal
State/province [108] 0 0
Faro
Country [109] 0 0
Portugal
State/province [109] 0 0
Lisboa
Country [110] 0 0
Portugal
State/province [110] 0 0
Lisbon
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Moscow
Country [112] 0 0
Singapore
State/province [112] 0 0
Singapore
Country [113] 0 0
South Africa
State/province [113] 0 0
Cape Town
Country [114] 0 0
South Africa
State/province [114] 0 0
Durban
Country [115] 0 0
South Africa
State/province [115] 0 0
Johannesburg
Country [116] 0 0
South Africa
State/province [116] 0 0
Lynnwood
Country [117] 0 0
Spain
State/province [117] 0 0
Alzira
Country [118] 0 0
Spain
State/province [118] 0 0
Barcelona
Country [119] 0 0
Spain
State/province [119] 0 0
Granada
Country [120] 0 0
Spain
State/province [120] 0 0
Guadalajara
Country [121] 0 0
Spain
State/province [121] 0 0
Huelva
Country [122] 0 0
Spain
State/province [122] 0 0
Jaen
Country [123] 0 0
Spain
State/province [123] 0 0
La Coruna
Country [124] 0 0
Spain
State/province [124] 0 0
La Laguna
Country [125] 0 0
Spain
State/province [125] 0 0
Las Palmas de Gran Canaria
Country [126] 0 0
Spain
State/province [126] 0 0
Las Palmas
Country [127] 0 0
Spain
State/province [127] 0 0
Madrid
Country [128] 0 0
Spain
State/province [128] 0 0
Orense
Country [129] 0 0
Spain
State/province [129] 0 0
Pontevedra
Country [130] 0 0
Spain
State/province [130] 0 0
Sabadell
Country [131] 0 0
Spain
State/province [131] 0 0
Santa Cruz de Tenerife
Country [132] 0 0
Spain
State/province [132] 0 0
Sevilla
Country [133] 0 0
Spain
State/province [133] 0 0
Toledo
Country [134] 0 0
Spain
State/province [134] 0 0
Valencia
Country [135] 0 0
Spain
State/province [135] 0 0
Vigo Pontevedra
Country [136] 0 0
Spain
State/province [136] 0 0
Zaragoza
Country [137] 0 0
Sweden
State/province [137] 0 0
Linkoping
Country [138] 0 0
Sweden
State/province [138] 0 0
Malmo
Country [139] 0 0
Sweden
State/province [139] 0 0
Molndal
Country [140] 0 0
Sweden
State/province [140] 0 0
Stockholm
Country [141] 0 0
Sweden
State/province [141] 0 0
Umea
Country [142] 0 0
Sweden
State/province [142] 0 0
Uppsala
Country [143] 0 0
Switzerland
State/province [143] 0 0
Aarau
Country [144] 0 0
Switzerland
State/province [144] 0 0
Basel
Country [145] 0 0
Switzerland
State/province [145] 0 0
Bern
Country [146] 0 0
Switzerland
State/province [146] 0 0
Chur
Country [147] 0 0
Switzerland
State/province [147] 0 0
Lausanne
Country [148] 0 0
Switzerland
State/province [148] 0 0
Mendrisio
Country [149] 0 0
Switzerland
State/province [149] 0 0
St. Gallen
Country [150] 0 0
Switzerland
State/province [150] 0 0
Zurich
Country [151] 0 0
Thailand
State/province [151] 0 0
Bangkok
Country [152] 0 0
United Kingdom
State/province [152] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Breast International Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
NCIC Clinical Trials Group
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
International Breast Cancer Study Group
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00045032
Trial related presentations / publications
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. Review.
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. Epub 2007 Jul 28.
Public notes

Contacts
Principal investigator
Name 0 0
Martine J. Piccart-Gebhart, MD, PhD
Address 0 0
Jules Bordet Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications