S0230 Goserelin in Preventing Ovarian Failure in Women Receiving Chemotherapy for Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Goserelin blocks hormone production in the ovaries. It is not yet known whether ovarian suppression using goserelin will prevent ovarian failure (early menopause) in women receiving chemotherapy for breast cancer. PURPOSE: This randomized phase III trial is studying how well giving goserelin together with chemotherapy works compared with chemotherapy alone in preventing early menopause in women with stage I, stage II, or stage IIIA breast cancer.

Detailed Description
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OBJECTIVES: Primary Compare the rate of premature ovarian failure in women with stage I-IIIA hormone receptor-negative breast cancer treated with chemotherapy with vs without goserelin. Secondary Compare the rate of ovarian dysfunction in patients treated with these regimens. Compare ovarian reserve in patients treated with these regimens. Describe the pregnancy rates in patients treated with these regimens. OUTLINE: This is a randomized study. Patients are stratified according to age (under 40 vs 40 to 49) and planned chemotherapy regimen (3- to 4-month/course anthracycline-based vs 6- to 8-month/course anthracycline-based vs 3- to 4-month/course non-anthracycline-based vs 6- to 8-month/course non-anthracycline-based). Patients are randomized to 1 of 2 treatment arms. Arm 1: Patients receive cyclophosphamide-containing chemotherapy alone. Patients are followed at 1, 2, and 5 years. Arm 2: Patients receive goserelin subcutaneously once every 4 weeks beginning 1 week before start of cyclophosphamide-containing chemotherapy. Treatment continues until completion of chemotherapy in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 416 patients (208 per treatment arm) will be accrued for this study within 3 years.

Official Title
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Phase III Trial of LHRH Analog Administration During Chemotherapy to Reduce Ovarian Failure Following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer

Conditions
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Breast Cancer, Infertility, Menopausal Symptoms

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: goserelin acetate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive breast cancer Stage I-IIIA Operable disease Bilateral synchronous invasive breast cancer allowed provided primary tumors were diagnosed no more than 1 month apart and both tumors are hormone receptor negative Must be planning to receive 3-8 months of a preoperative or postoperative chemotherapy regimen containing alkylating agents (anthracyclines or non-anthracyclines), meeting 1 of the following criteria: 3-month/4-course anthracycline-based regimen 6- to 8-month/course anthracycline-based regimen 6- to 8-month/course non-anthracycline-based regimen Hormone receptor status: Estrogen receptor negative Progesterone receptor negative PATIENT CHARACTERISTICS: Age 18 to 49 Sex Female Menopausal status Premenopausal Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Fertile patients must use effective barrier contraception No other prior malignancy except adequately treated basal cell or squamous cell skin cancer or any in situ cancer from which the patient has been disease-free for at least 5 years after treatment with curative intent PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No prior cytotoxic chemotherapy Endocrine therapy No other concurrent hormonal therapy Radiotherapy Concurrent radiotherapy to the breast, chest wall, or lymph nodes allowed Surgery See Disease Characteristics Other Concurrent participation in other therapeutic clinical trials, including SWOG-S0221, allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Chemotherapy<br>Patients receive cyclophosphamide-containing chemotherapy alone. | Drug: cyclophosphamide<br>* Part of planned chemotherapy regimen<br>|
| Experimental: Chemotherapy Plus Goserelin<br>Patients receive goserelin subcutaneously once every 4 weeks beginning 1 week before start of cyclophosphamide-containing chemotherapy. Treatment continues until completion of chemotherapy in the absence of disease progression or unacceptable toxicity. | Drug: cyclophosphamide<br>* Part of planned chemotherapy regimen<br>Drug: goserelin acetate<br>* Given subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Premature Ovarian Failure at 2 Years | Ovarian failure at two years is defined as amenorrhea (absence of menstrual bleeding) for the preceding six months AND the presence of follicle-stimulating hormone (FSH) in the post-menopausal range. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Ovarian Dysfunction at 2 Years | Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range. | 2 years | 
| Rate of Ovarian Dysfunction at 1 Year | Ovarian dysfunction is defined as amenorrhea for the preceding three months and the presence of FSH, estradiol and/or inhibin B levels in the postmenopausal range. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infertility, menopausal symptoms, stage II breast cancer, stage IIIA breast cancer, stage IA breast cancer, stage IB breast cancer, estrogen receptor-negative breast cancer, progesterone receptor-negative breast cancer