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Phase III Randomized Study of Trastuzumab (Herceptin®) Versus No Herceptin in Women With HER-2 Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Published Results Related Publications Trial Contact Information Registry Information
Alternate Title
Trastuzumab in Treating Women With Primary Breast Cancer
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
---|
Phase III | Treatment | Closed | 18 and over | BIG-01-01 EU-20216, ROCHE-B016348E, ROCHE-B016348C, EORTC-10011, CAN-NCIC-MA24, IBCSG-28-02, NCT00045032, MA24 |
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.
Entry 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
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/m2 or epirubicin
more than 720 mg/m2
- 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
Patient Characteristics:
Age Sex Menopausal status Performance status Life expectancy Hematopoietic - WBC at least 2,500/mm3
- Absolute neutrophil count at least 1,500/mm3
- 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
Expected Enrollment Approximately 4,482 patients (1,494 per treatment arm) will be accrued for this study within 4 years. Outcomes Primary Outcome(s)Disease-free survival Relapse-free survival Distant disease-free survival Incidence of cardiac dysfunction Safety and tolerability
Secondary Outcome(s)Overall survival Time to recurrence Time to distant recurrence
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. Published ResultsDowsett M, Procter M, McCaskill-Stevens W, et al.: 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.[PUBMED Abstract] Untch M, Gelber RD, Jackisch C, et al.: Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial. Ann Oncol 19 (6): 1090-6, 2008.[PUBMED Abstract] 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. Smith I, Procter M, Gelber RD, et al.: 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369 (9555): 29-36, 2007.[PUBMED Abstract] Suter TM, Procter M, van Veldhuisen DJ, et al.: Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol 25 (25): 3859-65, 2007.[PUBMED Abstract] Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353 (16): 1659-72, 2005.[PUBMED Abstract] Related PublicationsJahanzeb M: Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer 8 (4): 324-33, 2008.[PUBMED Abstract] Shiroiwa T, Fukuda T, Shimozuma K, et al.: 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 109 (3): 559-66, 2008.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations Breast International Group | | | Martine Piccart-Gebhart, MD, PhD, Protocol chair | | | |
European Organization for Research and Treatment of Cancer | | | Robert Coleman, MD, FRCP, Protocol chair | | | |
NCIC-Clinical Trials Group | | | Karen Gelmon, MD, Protocol chair | | | | Kathleen Pritchard, MD, Protocol co-chair | | | |
International Breast Cancer Study Group | | | Olivia Pagani, MD, Protocol chair | | | |
Registry Information | | Official Title | | 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 | | Trial Start Date | | 2001-12-01 | | Registered in ClinicalTrials.gov | | NCT00045032 | | Date Submitted to PDQ | | 2002-06-19 | | Information Last Verified | | 2007-01-03 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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