Condition category
Cancer
Date applied
15/10/2002
Date assigned
15/10/2002
Last edited
31/08/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr - -

ORCID ID

Contact details

UKCCCR Register Co-ordinator
MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00045032

Protocol/serial number

N/A

Study information

Scientific title

Acronym

HERA

Study hypothesis

Added 08/09/09:
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether trastuzumab is effective in treating primary breast cancer in women who have completed adjuvant chemotherapy.

Primary objectives:
1. Compare the disease-free survival of women with HER2-positive primary breast cancer treated with trastuzumab (Herceptin®) for 1 year vs trastuzumab for 2 years vs standard supportive care.
2. Compare the overall survival of patients treated with these regimens.
3. Compare the relapse-free survival of patients treated with these regimens.
4. Compare the distant disease-free survival of patients treated with these regimens.
5. Compare the incidence of cardiac dysfunction in patients treated with these regimens.
6. Evaluate the safety and tolerability of these regimens in these patients.

Secondary objectives:
1. Compare time to recurrence in patients treated with these regimens.
2. Compare time to distant recurrence in patients treated with these regimens.
3. Compare outcomes, in terms of disease-free survival, overall survival, recurrence-free survival, distant disease-free survival, time to recurrence, time to distant recurrence, cardiac safety, and overall safety, in patients treated with trastuzumab for 1 year vs 2 years.

Please note that as of 08/09/09 this record has been extensively updated. All updates can be found under the relevant field with the above update date.

Ethics approval

Not provided at time of registration

Study design

Multicentre randomised open label controlled parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Breast cancer

Intervention

Current information as of 08/09/09:
This is a randomised, open-label, multicentre study. Patients are stratified according to nodal status (any nodal status and prior neoadjuvant chemotherapy vs no positive nodes and no prior neoadjuvant chemotherapy vs 1-3 positive nodes and no prior neoadjuvant chemotherapy vs 4 or more positive nodes and no prior neoadjuvant chemotherapy), prior adjuvant chemotherapy regimen (no anthracyclines or taxanes vs anthracyclines only vs anthracyclines and taxanes), receptor status and endocrine therapy (negative vs positive and no prior endocrine therapy vs positive and prior endocrine therapy), age (18 to 34 vs 35 to 49 vs 50 to 59 vs 60 and over), and participating center. Patients are randomized to 1 of 3 treatment arms.

1. Arm I: Patients receive trastuzumab (Herceptin®) IV over 1.5 hours on day 1. Courses repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
2. Arm II: Patients receive trastuzumab as in arm I. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
3. Arm III: Patients receive no trastuzumab. Patients may later receive trastuzumab as in arm I or arm II. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Initial information at time of registration
1. Patients are randomised to receive Herceptin® every 3 weeks for 1 or 2 years
2. No further treatment

Intervention type

Drug

Phase

Phase III

Drug names

Tratuzumab (Herceptin®)

Primary outcome measures

Added 08/09/09:
1. Disease-free survival
2. Relapse-free survival
3. Distant disease-free survival
4. Incidence of cardiac dysfunction
5. Safety and tolerability

Secondary outcome measures

Added 08/09/09:
1. Overall survival
2. Time to recurrence
3. Time to distant recurrence

Overall trial start date

01/03/2002

Overall trial end date

01/12/2004

Reason abandoned

Eligibility

Participant inclusion criteria

1. Females aged ≥18 years
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
3. Non-metastatic operable primary invasive adenocarcinoma of the breast that is histologically confirmed, adequately excised and axillary node positive or negative
4. Known hormone receptor status
5. Completion of at least 3 months of an approved (neo-) adjuvant chemotherapy regimen
6. Baseline left ventricular ejection fraction (LVEF) ≥55%
7. Completion of radiotherapy for any patients undergoing radiotherapy
8. Overexpression of HER2 in the invasive component of the primary tumour
9. Completion of all necessary baseline lab and radiological investigations
10. Signed written informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

3192

Participant exclusion criteria

Does not match inclusion criteria

Recruitment start date

01/03/2002

Recruitment end date

01/12/2004

Locations

Countries of recruitment

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

Trial participating centre

UKCCCR Register Co-ordinator
London
NW1 2DA
United Kingdom

Sponsor information

Organisation

Roche Products Limited (UK)

Sponsor details

P.O. Box 8
Welwyn Garden City
Hertfordshire
AL7 3AY
United Kingdom

Sponsor type

Industry

Website

http://www.roche.com

Funders

Funder type

Industry

Funder name

Roche Products Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2005 results in http://www.ncbi.nlm.nih.gov/pubmed/16236737
2. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17208639
3. 2007 results on adverse cardiac effects in http://www.ncbi.nlm.nih.gov/pubmed/17646669
4. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18296421
5. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19364966
6. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20530280

Publication citations

  1. Results

    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Rüschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD, , Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer., N. Engl. J. Med., 2005, 353, 16, 1659-1672, doi: 10.1056/NEJMoa052306.

  2. Results

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

  3. Results on adverse cardiac effects

    Suter TM, Procter M, van Veldhuisen DJ, Muscholl M, Bergh J, Carlomagno C, Perren T, Passalacqua R, Bighin C, Klijn JG, Ageev FT, Hitre E, Groetz J, Iwata H, Knap M, Gnant M, Muehlbauer S, Spence A, Gelber RD, Piccart-Gebhart MJ, Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial., J. Clin. Oncol., 2007, 25, 25, 3859-3865, doi: 10.1200/JCO.2006.09.1611.

  4. Results

    Untch M, Gelber RD, Jackisch C, Procter M, Baselga J, Bell R, Cameron D, Bari M, Smith I, Leyland-Jones B, de Azambuja E, Wermuth P, Khasanov R, Feng-Yi F, Constantin C, Mayordomo JI, Su CH, Yu SY, Lluch A, Senkus-Konefka E, Price C, Haslbauer F, Suarez Sahui T, Srimuninnimit V, Colleoni M, Coates AS, Piccart-Gebhart MJ, Goldhirsch A, , Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial., Ann. Oncol., 2008, 19, 6, 1090-1096, doi: 10.1093/annonc/mdn005.

  5. Results

    Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U, Rueschoff J, Jordan B, Dolci S, Abramovitz M, Stoss O, Viale G, Gelber RD, Piccart-Gebhart M, Leyland-Jones B, Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial., J. Clin. Oncol., 2009, 27, 18, 2962-2969, doi: 10.1200/JCO.2008.19.7939.

  6. Results

    Procter M, Suter TM, de Azambuja E, Dafni U, van Dooren V, Muehlbauer S, Climent MA, Rechberger E, Liu WT, Toi M, Coombes RC, Dodwell D, Pagani O, Madrid J, Hall M, Chen SC, Focan C, Muschol M, van Veldhuisen DJ, Piccart-Gebhart MJ, Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin Adjuvant (HERA) trial., J. Clin. Oncol., 2010, 28, 21, 3422-3428, doi: 10.1200/JCO.2009.26.0463.

Additional files

Editorial Notes