Triptorelin for Preserving Ovarian Function in Premenopausal Women Receiving Chemotherapy for Early-Stage Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as triptorelin, may protect normal ovarian cells from the side effects of chemotherapy. PURPOSE: This randomized phase II trial is studying how well triptorelin works in preserving ovarian function in premenopausal women who are receiving chemotherapy for early-stage breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the protective effect of chemical ovarian suppression using triptorelin on the preservation of ovarian function in premenopausal women with early-stage operable breast cancer undergoing adjuvant or neoadjuvant systemic chemotherapy. Secondary Determine the rate of chemotherapy-related amenorrhea in patients treated with this drug. Determine the value of inhibin A and B as alternative markers of premature ovarian failure in patients treated with this drug. Determine quality of life of patients treated with this drug. Determine disease-free and overall survival of patients treated with this drug. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (< 35 years vs 35 to 39 years vs > 39 years); concurrent neoadjuvant or adjuvant systemic chemotherapy (fluorouracil, epirubicin, and cyclophosphamide [6 courses] OR fluorouracil, doxorubicin, and cyclophosphamide [6 courses] vs doxorubicin and cyclophosphamide [AC] [4 courses] vs doxorubicin and cyclophosphamide [AC] [4 courses] followed by a taxane [4 courses]); and hormone receptor status (estrogen receptor [ER]- AND progesterone receptor [PR]-negative vs ER- OR PR-positive). Arm I: Beginning within 1-4 weeks before the start of chemotherapy, patients receive triptorelin intramuscularly once monthly for 4-6 months during neoadjuvant or adjuvant systemic chemotherapy. Arm II: Patients receive neoadjuvant or adjuvant systemic chemotherapy only. Quality of life is assessed at baseline, monthly during treatment, every 6 months for 2 years, and then annually for 3 years. Patients are followed every 6 months for 2 years and then annually for 3 years. PROJECTED ACCRUAL: A total of 138 patients (69 per treatment arm) will be accrued for this study within 35 months.

Official Title
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Preservation of Ovarian Function in Young Women Treated With (Neo) Adjuvant Chemotherapy for Breast Cancer: A Randomized Trial Using the Gonadotropin-releasing Hormone (GnRH) Agonist (Triptorelin) During Chemotherapy

Conditions
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Breast Cancer, Hormone Changes, Drug Toxicity

Intervention / Treatment
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* Drug: triptorelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Early-stage, operable disease Scheduled to receive adjuvant or neoadjuvant systemic chemotherapy for breast cancer Hormone receptor status: Meets 1 of the following criteria: Estrogen receptor (ER)- OR progesterone receptor (PR)-positive ER- AND PR-negative No history of premature ovarian failure PATIENT CHARACTERISTICS: Age Under 45 Sex Female Menopausal status Premenopausal Follicle-stimulating hormone levels < 40 IU/L at baseline AND at least 2 menstrual periods within the past 6 months No first-degree relative menopausal at < 40 years of age Performance status Eastern Cooperative Oncology Group [ECOG] 0-1 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Fertile patients must use effective non-hormonal methods of contraception No prior osteoporosis or other non-malignant systemic disease that would preclude prolonged follow-up No known allergies to gonadotrophin-releasing hormone agonists No other cancer except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No prior chemotherapy Endocrine therapy At least 2 weeks since prior oral contraceptives No prior fertility treatment Clomiphene or pergonal for polycystic ovarian disease allowed No other concurrent oral or transdermal hormonal therapy, including any of the following: Estrogen Progesterone Androgens Aromatase inhibitors Hormone replacement therapy Oral contraceptives Radiotherapy No prior ovarian radiotherapy Surgery No prior bilateral oophorectomy No plans for oophorectomy or hysterectomy within the next 2 years Other At least 1 week since prior warfarin Exclusion Criteria: History of premature ovarian failure Over 45 years of age First-degree relative menopausal at < 40 years of age Pregnant or nursing Prior osteoporosis or other non-malignant systemic disease that would preclude prolonged follow-up Known allergies to gonadotrophin-releasing hormone agonists Other cancer besides nonmelanoma skin cancer Prior chemotherapy Prior ovarian radiotherapy Prior bilateral oophorectomy

Ages Eligible for Study
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Maximum Age: 44 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 |
| --- | --- |
| Experimental: triptorelin<br>GnRH analogue (triptorelin) during chemotherapy | Drug: triptorelin<br>* 3.75 mg TRELSTAR DEPOT (triptorelin) administered monthly as single intramuscular injection<br>* Other names: Trelstar Depot;|
| No Intervention: no triptorelin<br>No GnRH analogue (triptorelin) during chemotherapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Resumption of Menses | Ovarian function as assessed by follicle stimulating hormone (FSH) and record of menses every 6 months beginning in month 6 for 2 years and then annually for 3 years | Baseline, end of chemotherapy then 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy-related Amenorrhea | Chemotherapy-related amenorrhea as assessed by record of menses monthly during treatment. Record of menses is completed by patient throughout their time on study through chemotherapy and for 5 years. | Baseline, end of chemotherapy then 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug/agent toxicity by tissue/organ, hormone changes, stage I breast cancer, stage II breast cancer