Goserelin Acetate Study for Ovarian Function in Patients With Primary Breast Cancer

Phase III Randomized Study of a Goserelin Acetate for Preservation of Ovarian Function in Patients With Primary Breast Cancer (PBC)

Primary Objective:

• To determine the effectiveness of goserelin acetate (Zoladex) in preserving ovarian function in premenopausal women undergoing neoadjuvant and/or adjuvant chemotherapy for primary invasive breast cancer by documenting persistence or resumption of regular menses.

Secondary Objectives:

• To determine the incidence of pregnancy and the effect for participants' quality of life (QOL) after chemotherapy.
• To determine the overall survival and disease-free survival times of study participants.

Goserelin is designed to block hormones that can regulate your menstruation by affecting the pituitary gland (part of brain).

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. You will either be assigned to receive goserelin or no treatment. There is an equal chance of being assigned to either group.

If you are assigned to receive goserelin, the first dose will be given as an injection under the skin, 1 week before you start chemotherapy. You will then receive chemotherapy as part of your standard of care. Following the first dose of goserelin, you will be given a goserelin injection into the skin, once a month until 3 weeks after the last chemotherapy dose.

You will be taken off study if intolerable side effects occur during this study. After you are finished with chemotherapy, you will have a series of follow-up visits. During the period of follow-up, you will have a medical history, physical exam, and blood tests (2-3 teaspoons) to evaluate your ovarian function, every 3 months for 1 year and then at 24 months. You will be asked to fill out questionnaires about your menstrual history at these visits. The questionnaires should take about 15 minutes to complete. You will be also asked to fill out questionnaires about your quality of life at 12 and 24 months. The questionnaires should take about 30 minutes to complete.

This is an investigational study. Goserelin is commercially available and has been approved by the FDA for use in breast cancer patients. Its use in this study is investigational. About 148 patients will take part in this multicenter study. Up to 36 patients will be enrolled at M.D. Anderson.

Inclusion Criteria:

1. Female patients older than 15 years and younger than 46 years.

2. Primary breast cancer (Stage I, II, or III).

3. Pathologically confirmed invasive breast carcinoma.

4. Negative hormone-receptor status. (Negative defined as ER- and PR- staining in less than 10% of tumor cells, or tumors with less than or equal to 3 fm/mg cytosol protein on ligand-binding or enzyme-linked immunoassay).

5. Premenopausal, verified before chemotherapy is begun as satisfying both:

   • Cyclic vaginal bleeding.
   • Follicle-stimulating hormone (FSH) is less than or equal to 15 IU/L. If patients are taking oral contraceptives, FSH must be measured 1-2 weeks after discontinuation. If FSH is greater than 15 and the patient has regular menses, gynecologic consultation will be required for a decision on premenopausal status.

6. Candidates for neoadjuvant and/or adjuvant chemotherapy for primary breast cancer.

7. Treatment with at least four (4) cycles of chemotherapy as planned.

8. Zubrod performance score of 0 or 1.

9. Must consent to preservation of their ovarian function and indicate their awareness of the investigational nature of this study, in keeping with institutional policy.

10. Willingness to use barrier contraception if sexually active.

Exclusion Criteria:

1. Pregnancy. Women must have a negative serum pregnancy test before initiation of injection.
2. Hypersensitivity to any GnRH analog.
3. Previous receipt of systemic chemotherapy.
4. To receive at least 4 cycles of neoadjuvant and/or adjuvant chemotherapy with CMF.
5. Stage IV breast cancer.
6. Prothrombin time (PT) and partial prothrombin time (PTT) with INR > 1.5
7. Platelets < 50,000/mm^3