Goserelin for Ovarian Protection in Premenopausal Patients Receiving Cyclophosphamide

Study Overview
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Brief Summary
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The use of adjuvant chemotherapy in younger women with early breast cancer (EBC) has substantially improved the long-term outcome. However, this benefit is associated with long-term toxic effects which are becoming more important as prognosis improves. These include premature menopause and infertility in young pre-menopausal women. The incidence of premature menopause depends on the type and intensity of chemotherapy and the patient's age. In women <35 years old, the long-term (3 years after diagnosis) incidence of amenorrhea is similar to women who have not received chemotherapy, at ∼ 10%, but this increases to 50% in women between 35 and 40 years old, and can be up to 85% in women >40 years. Premature ovarian failure has major consequences including sexual dysfunction and infertility, and the latter may be of great concern to younger patients with breast cancer and has a bearing in influencing treatment decisions in almost 30% of cases. Currently, there is no standard treatment for preventing chemotherapy-induced ovarian failure. Previous studies have suggested that temporary ovarian suppression with a gonadotropin-releasing hormone (GnRH) analogue may preserve ovarian function both in humans and animal models. Clinical data are conflicting. For example, a recent Italian multi-center phase III study Prevention of Menopause-Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mamella 6 (PROMISE-GIM6) reported that the use of GnRH analogue, triptorelin during chemotherapy in pre-menopausal patients with EBC, reduced the occurrence of chemotherapy-induced early menopause with four pregnancies after a 26-month follow-up [one in the chemotherapy alone arm and three in the triptorelin with chemotherapy arm]. In contrast, another trial suggested that the use of goserelin concurrently with neoadjuvant chemotherapy did not significantly reduce incidence of amenorrhea 6 months after the end of chemotherapy compared with those receiving chemotherapy alone and only two pregnancies were recorded [one in each arm] with a follow-up of 2 years.

Detailed Description
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In this phase II trial, patients will be randomly assigned, in a 1:1 ratio, to standard adjuvant or neoadjuvant chemotherapy with the GnRH agonist goserelin (goserelin group) or to chemotherapy without goserelin (chemotherapy alone group). For Patients randomly assigned to the goserelin group, goserelin at a dose of 3.6 mg will be administered subcutaneously every 4 weeks beginning 1 week before the initial chemotherapy dose and will be continued to within 2 weeks before or after the final chemotherapy dose. Follow up: All patients will be followed for at least 1 year clinically monthly and by laboratory assessment by hormonal profile (FSH, LH, E2) every 6 months.

Official Title
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Phase II Study of Goserelin for Ovarian Protection in Premenopausal Patients Receiving Cyclophosphamide Containing Chemotherapy: Menstruation Outcome

Conditions
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Ovarian Failure

Intervention / Treatment
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* Drug: Goserelin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal cancer patients who will receive Cyclophosphamide-containing chemotherapy. Exclusion Criteria: postmenopausal cancer patients. cancer patients who will receive non Cyclophosphamide containing chemotherapy.
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: chemotherapy without goserelin<br>these patients will receive their chemotherapy without addition of Goserelin | |
| Experimental: chemotherapy with goserelin<br>these patients will receive their chemotherapy with addition of Goserelin | Drug: Goserelin<br>* adding goserelin with chemotherapy<br>* Other names: zoladex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| compare rate of ovarian failure at 1 year between the two treatment groups | rate of ovarian failure | 1 year |