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
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
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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.
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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.
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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.
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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.
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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.
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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.