Phase III Randomized Study of Trastuzumab (Herceptin) With or Without Tamoxifen in Women With Progressive, Stage IV, Estrogen or Progesterone Receptor- and HER2/Neu-Positive Breast Cancer
18 Years
N/A
Both
Stage IV Breast Cancer, Recurrent Breast Cancer
Trial Information
Phase III Randomized Study of Trastuzumab (Herceptin) With or Without Tamoxifen in Women With Progressive, Stage IV, Estrogen or Progesterone Receptor- and HER2/Neu-Positive Breast Cancer
OBJECTIVES:
- Compare time to progression in women with progressive, stage IV, estrogen or
progesterone receptor- and HER2/neu-positive breast cancer treated with trastuzumab
(Herceptin) with or without tamoxifen.
- Correlate response with type of measurement (immunohistochemistry or fluorescent in
situ hybridization) of HER2/neu expression in patients treated with these regimens.
- Compare objective response rate (complete or partial response) in patients treated with
these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to prior adjuvant
treatment (yes vs no), ECOG performance status (0-1 vs 2), and prior aromatase inhibitor
treatment (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive trastuzumab (Herceptin) IV over 60-90 minutes on day 1.
- Arm II: Patients receive trastuzumab as in arm I and oral tamoxifen once daily on days
1-21.
In both arms, treatment repeats every 3 weeks for at least 2 courses in the absence of
disease progression or unacceptable toxicity.
Patients are followed every 3 months for 5 years.
PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this
study within 28 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed invasive stage IV breast cancer
- Hormone receptor status:
- HER2/neu positive (3+ by immunohistochemical [IHC] assay or fluorescent in situ
hybridization [FISH])
- Estrogen receptor or progesterone receptor positive
- Measurable or evaluable disease
- Must have disease progression within 6 months of initiation of tamoxifen
(administered in the adjuvant or metastatic setting) or during aromatase inhibitor
therapy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Female
Menopausal status
- Not specified
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 75,000/mm^3
Hepatic
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- SGOT and SGPT no greater than 2.5 times ULN
Renal
- Not specified
Cardiovascular
- LVEF normal by MUGA
Other
- Not pregnant or nursing
- Fertile patients must use effective nonhormonal contraception during and for at least
2 months after study completion
- No other concurrent active malignancy except nonmelanoma skin cancer
- Patients who have completed prior therapy and are at less than 30% risk of relapse
are not considered to have an active malignancy
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior trastuzumab (Herceptin) in the adjuvant or metastatic setting
Chemotherapy
- No more than 1 prior chemotherapy regimen in the metastatic setting
- No concurrent chemotherapy
Endocrine therapy
- See Disease Characteristics
- No more than 1 prior hormonal therapy regimen for metastatic disease
- Prior aromatase inhibitor therapy administered in the first-line metastatic or
adjuvant setting is allowed provided there is disease progression on tamoxifen
- No other concurrent hormonal therapy except the following:
- Steroids for adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)
- Intermittent use of dexamethasone as an antiemetic
- Vaginal estrogen (or Estring®) for vaginal dryness
Radiotherapy
- No concurrent palliative radiotherapy except whole brain irradiation for CNS disease
Surgery
- Not specified
Other
- Concurrent bisphosphonates allowed
- No concurrent cardioprotective drugs
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Joanne E. Mortimer, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sentara Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000269409
NCT ID:
NCT00053339
Start Date:
Completion Date:
Related Keywords:
- Stage IV Breast Cancer
- Recurrent Breast Cancer
- Breast Neoplasms
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