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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:
ClinicalTrials.gov Identifier:
NCT00045032
First Posted: January 27, 2003
Last Update Posted: April 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
Results First Submitted: October 19, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Breast Cancer
Intervention: Drug: Herceptin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After the release of initial study results, participants in the Observation Arm without disease recurrence were given the opportunity to cross over to receive 1 or 2 years of adjuvant Herceptin. Efficacy analyses were still performed according to original randomization.

Reporting Groups
  Description
Observation Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy were 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 was provided.
Herceptin 1-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 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 for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 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 for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.

Participant Flow:   Overall Study
    Observation Arm   Herceptin 1-Year Arm   Herceptin 2-Year Arm
STARTED   1697 [1]   1702 [1]   1700 [1] 
Crossover to Adjuvant Herceptin   888   0 [2]   0 [2] 
COMPLETED   834   994   974 
NOT COMPLETED   863   708   726 
Adverse Event/Intercurrent Illness                2                2                7 
Death                22                24                17 
Insufficient Therapeutic Response                542                437                445 
Violation of Selection Criteria at Entry                3                6                6 
Other Protocol Violation                2                0                1 
Refused/Did Not Cooperate/Withdrew                142                93                84 
Failure to Return                57                62                61 
Not Specified                93                84                105 
[1] Included all participants with available signed Informed Consent Form.
[2] This milestone is not applicable to participants who were already randomized to Herceptin.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS) Population: All enrolled/randomized participants who had an available signed Informed Consent Form.

Reporting Groups
  Description
Observation Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy were 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 was provided.
Herceptin 1-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 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 for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 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 for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Total Total of all reporting groups

Baseline Measures
   Observation Arm   Herceptin 1-Year Arm   Herceptin 2-Year Arm   Total 
Overall Participants Analyzed 
[Units: Participants]
 1697   1702   1700   5099 
Age 
[Units: Years]
Mean (Standard Deviation)
 49.2  (10.08)   49.0  (10.06)   49.2  (10.09)   49.1  (10.08) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      1697 100.0%      1702 100.0%      1700 100.0%      5099 100.0% 
Male      0   0.0%      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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) ]

2.  Primary:   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) ]

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

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

5.  Primary:   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) ]

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

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

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

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

10.  Primary:   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) ]

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

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

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

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

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

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

17.  Secondary:   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) ]

18.  Secondary:   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 ]

19.  Secondary:   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) ]

20.  Secondary:   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) ]

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

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

23.  Secondary:   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) ]

24.  Secondary:   OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up   [ Time Frame: Years 3, 5, 7, 8 ]

25.  Secondary:   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) ]

26.  Secondary:   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 ]

27.  Secondary:   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) ]

28.  Secondary:   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 ]

29.  Secondary:   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) ]

30.  Secondary:   RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up   [ Time Frame: Years 3, 5, 7, 8 ]

31.  Secondary:   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) ]

32.  Secondary:   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 ]

33.  Secondary:   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) ]

34.  Secondary:   DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up   [ Time Frame: Years 3, 5, 7, 8 ]

35.  Secondary:   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) ]

36.  Secondary:   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 ]

37.  Secondary:   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) ]

38.  Secondary:   TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up   [ Time Frame: Years 3, 5, 7, 8 ]

39.  Secondary:   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) ]

40.  Secondary:   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 ]

41.  Secondary:   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) ]

42.  Secondary:   DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up   [ Time Frame: Years 3, 5, 7, 8 ]

43.  Secondary:   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) ]

44.  Secondary:   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 ]

45.  Secondary:   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) ]

46.  Secondary:   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 ]

47.  Secondary:   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) ]

48.  Secondary:   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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: global-roche-genentech-trials@gene.com


Publications of Results:
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.

Other Publications:
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
First Submitted: September 6, 2002
First Posted: January 27, 2003
Results First Submitted: October 19, 2016
Results First Posted: April 27, 2017
Last Update Posted: April 27, 2017