Trastuzumab With or Without Tamoxifen in Treating Women With Progressive Stage IV Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. Combining trastuzumab with tamoxifen may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of trastuzumab with or without trastuzumab in treating women who have invasive stage IV breast cancer.

Detailed Description
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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.

Official Title
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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

Conditions
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Stage IV Breast Cancer, Recurrent Breast Cancer

Intervention / Treatment
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* Drug: tamoxifen
* Drug: trastuzumab


Participation Criteria
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Eligibility Criteria
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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 Performance status ECOG 0-2 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 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 EstringÂ®) for vaginal dryness Radiotherapy No concurrent palliative radiotherapy except whole brain irradiation for CNS disease Other Concurrent bisphosphonates allowed No concurrent cardioprotective drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: trastuzumab<br>Patients receive trastuzumab (Herceptin) IV over 60-90 minutes on day 1. 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. | Drug: trastuzumab<br> <br> |
| Experimental: trastuzumab + tamoxifen<br>Patients receive trastuzumab V over 60-90 minutes on day 1 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. | Drug: tamoxifen<br> <br> Drug: trastuzumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response |  | Up to 5 years | 
| response rate |  | Up to 5 years |