HERA: A Randomised Three-Arm Multi-Centre 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
18 Years
N/A
Female
Breast Cancer
Trial Information
HERA: A Randomised Three-Arm Multi-Centre 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
OBJECTIVES:
Primary
- 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.
- Compare the overall survival of patients treated with these regimens.
- Compare the relapse-free survival of patients treated with these regimens.
- Compare the distant disease-free survival of patients treated with these regimens.
- Compare the incidence of cardiac dysfunction in patients treated with these regimens.
- Evaluate the safety and tolerability of these regimens in these patients.
Secondary
- Compare time to recurrence in patients treated with these regimens.
- Compare time to distant recurrence in patients treated with these regimens.
- 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.
OUTLINE: This is a randomized, open-label, multicenter 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.
- 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.
- 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.
- 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.
PROJECTED ACCRUAL: Approximately 4,482 patients (1,494 per treatment arm) will be accrued
for this study within 4 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed nonmetastatic primary invasive adenocarcinoma of the breast
- Adequately excised
- Axillary nodes positive or negative
- No positive or suspicious internal mammary nodes identified by sentinel node
technique that have not been irradiated
- No supraclavicular lymph node involvement
- HER2-positive disease with one of the following:
- 3+ overexpression by immunohistochemistry (IHC)
- 2+ overexpression by IHC and fluorescence in situ hybridization (FISH) with
c-erbB2 gene amplification
- c-erbB2 gene amplification by FISH
- Previously treated with at least 3 months or 4 courses of approved neoadjuvant or
adjuvant chemotherapy with or without radiotherapy
- No synchronous bilateral or multifocal breast cancer that is not HER2-positive
- No locally advanced or inflammatory breast cancer
- No clinical T4 primary breast tumor
- Prior curatively treated ipsilateral ductal carcinoma in situ of the breast is
allowed
- Hormone receptor status:
- Estrogen receptor and progesterone receptor status known OR
- Estrogen receptor status known
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Female
Menopausal status
- Not specified
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- WBC at least 2,500/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000
Hepatic
- Bilirubin no greater than 2 times upper limit of normal (ULN)
- AST and ALT no greater than 2.5 times ULN
- Alkaline phosphatase no greater than 2.5 times ULN
Renal
- Creatinine no greater than 2 times ULN
Cardiovascular
- LVEF at least 55% by echocardiography or MUGA
- No serious cardiac illness
- No documented congestive heart failure
- No high-risk uncontrolled arrhythmias
- No angina pectoris requiring antianginal medication
- No clinically significant valvular heart disease
- No evidence of transmural infarction on EKG
- No poorly controlled hypertension (i.e., systolic greater than 180 mm Hg or diastolic
greater than 100 mm Hg)
Pulmonary
- No severe pulmonary disease/illness
Other
- No other malignancy except for curatively treated basal cell or squamous cell skin
cancer, carcinoma in situ of the cervix, or other cancer that has been curatively
treated, with no evidence of disease, and has less than 15% risk of recurrence over
the next 10 years
- No other concurrent serious disease that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior peripheral stem cell or bone marrow stem cell transplantation as part of
prior neoadjuvant or adjuvant chemotherapy regimen
- No prior biologic therapy or immunotherapy for breast cancer
- No prior anti-HER2 therapy for any reason
- No concurrent immunotherapy for breast cancer
Chemotherapy
- See Disease Characteristics
- See Biologic therapy
- No prior cumulative dose of doxorubicin more than 360 mg/m^2 or epirubicin more than
720 mg/m^2
- No prior anthracyclines for another malignancy
- No more than 7 weeks since day 1 of last chemotherapy course
- No concurrent adjuvant chemotherapy
Endocrine therapy
- No concurrent hormonal therapy, including aromatase inhibitors, pure antiestrogens,
or progestational agents, for breast cancer
- Concurrent systemic adjuvant hormonal therapy for estrogen receptor-positive patients
allowed
- Concurrent tamoxifen allowed
Radiotherapy
- See Disease Characteristics
- No more than 6 weeks since completion of prior radiotherapy
- No prior mediastinal irradiation except for internal mammary node irradiation for the
present breast cancer
Surgery
- See Disease Characteristics
- No more than 6 weeks since prior definitive surgery
- Concurrent ovarian ablation allowed
Other
- No other concurrent investigational therapy for breast cancer
- Concurrent bisphosphonate therapy allowed if started prior to study
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Disease-free survival
Safety Issue:
No
Principal Investigator
Martine J. Piccart-Gebhart, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Institut Jules Bordet
Authority:
Sweden: Swedish Medical Products Agency
Study ID:
BO16348
NCT ID:
NCT00045032
Start Date:
December 2001
Completion Date:
September 2015
Related Keywords:
- Breast Cancer
- stage I breast cancer
- stage II breast cancer
- stage IIIA breast cancer
- Breast Neoplasms
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