Goserelin in Preventing Early Menopause in Premenopausal Women Undergoing Chemotherapy for Stage I, Stage II, or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Goserelin may help prevent early menopause in patients undergoing chemotherapy for breast cancer. It is not yet known whether goserelin is effective in preventing early menopause in women undergoing chemotherapy for breast cancer. PURPOSE: This randomized phase III trial is studying goserelin to see how well it works compared with no goserelin in preventing early menopause in premenopausal women undergoing chemotherapy for stage I, stage II, or stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary Compare the incidence of premature ovarian failure after chemotherapy in premenopausal women with stage I-III breast cancer treated with goserelin vs no goserelin . Secondary Compare the quality of life of patients treated with these regimens. Compare menopausal symptoms in patients treated with these regimens. Compare bone mineral density loss in patients treated with these regimens. Compare hormone levels in patients treated with these regimens. Compare menstruation in patients treated with these regimens. Compare the incidence of pregnancy in patients treated with these regimens. OUTLINE: This is a randomized, open-label, prospective, parallel group, multicenter study. Patients are stratified according to age (≤ 40 years vs > 40 years) and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I (chemotherapy alone): Patients receive neoadjuvant or adjuvant cyclophosphamide- and/or anthracycline-containing chemotherapy. Treatment continues for 6-8 courses in the absence of disease progression or unacceptable toxicity. Arm II (chemotherapy plus goserelin for ovarian function suppression): Patients receive neoadjuvant or adjuvant chemotherapy as in arm I. Patients also receive goserelin subcutaneously every 3-4 weeks beginning 1-3 weeks before the start of chemotherapy. Treatment with goserelin repeats every 3-4 weeks until completion of chemotherapy. Quality of life is assessed at baseline, at 3, 6, 12, 18, and 24 months, and then annually for up to 5 years. After completion of study therapy, patients are followed periodically for 5 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Official Title
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Ovarian Protection Trial In Premenopausal Breast Cancer Patients [OPTION]

Conditions
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Menopausal Symptoms, Breast Cancer, Infertility

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: goserelin acetate
* Procedure: adjuvant therapy
* Procedure: fertility assessment and management
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive breast cancer Stages I-IIIB with node-positive or -negative disease (N0-2) Operable disease Must meet 1 of the following criteria: Has undergone mastectomy or breast-conserving surgery with complete excision of primary tumor within the past 8 weeks Scheduled to receive neoadjuvant chemotherapy No metastatic breast cancer, including supraclavicular fossa metastases Hormone receptor status meeting 1 of the following criteria: Estrogen receptor (ER) and progesterone receptor poor or negative AND not a candidate for adjuvant endocrine therapy ER positive AND no requirement for ovarian suppression as a necessary part of treatment PATIENT CHARACTERISTICS: Female Premenopausal with regular menses in the 12 months preceding surgery No other prior or concurrent invasive malignancy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix Suitable fitness status for chemotherapy Adequate hepatic, renal, and bone marrow function Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or endocrine therapy
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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclophosphamide|nan|
|Drug: goserelin acetate|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: fertility assessment and management|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of premature menopause, defined as cessation of menses during a course of chemotherapy with no recovery for at least 12 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of menopausal symptoms |  |  | 
| Quality of life |  |  | 
| Bone mineral density loss as measured by dual energy X-ray absorptiometry scans at 12, 24, and 36 months and by serum biomarkers |  |  | 
| Hormone levels (including follicle-stimulating hormone, luteinizing hormone, beta-inhibin, and estradiol) as measured after course 3, after course 6 or 8 (depending on chemotherapy regimen), at 9 and 12 months, and then annually for up to 5 years |  |  | 
| Menstruation history as measured by patient menstrual diary for 24 months from the start of chemotherapy |  |  | 
| Incidence of pregnancy |  |  | 

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