Gonadotropin-Releasing Hormone Agonist for the Preservation of Ovarian Function During Chemotherapy in Premenopausal Breast Cancer (POF)

The study is a prospective randomized control clinical trial which is sponsored by the researchers. The purpose of this study is to determine the effectiveness of Gonadotropin-Releasing hormone agonist on ovarian function for premenopausal breast cancer patients during chemotherapy. The premenopausal breast cancer patients will be randomly (1:1) enrolled to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy alone group). All patients are stratified according to age (<35years vs.36-44years), hormone receptor status (HR+ or ER+ vs.HR- and ER-), chemotherapy regimen(3-4 cycles vs.6-8 cycles, and cyclophosphamide-based vs.noncyclophosphamide).The follow-up time will be at least 2years. The ovarian failure, follicle-stimulating hormone, estradiol and anti-Mullerian hormone, pregnancy outcomes and disease-free and overall survival will be compared between two groups to evaluate the effectiveness of protect against ovarian failure.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: goserelin; Drug: standard chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• The patients signed the written informed consent.
• Histologically proven stage I, II, or III breast cancer
• Must be candidates for adjuvant or neoadjuvant chemotherapy,
• Must be premenopausal.
• Trastuzumab is permitted in patients with human epidermal growth factor receptor 2 (HER2) overexpressing tumors.

Exclusion Criteria:

• The patients were previous chemotherapy;
• Evidence of distant metastases;
• Other malignancies in the previous 5 years.
• The patients were using GnRHa, progesterone, stimulate ovulation drugs, oral contraceptives, aromatase inhibitors, intrauterine device with hormone, subcutaneous preparations contraceptive drugs such as hormone drugs and instruments during 3 month preceding the start of chemotherapy.
• Pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: standard chemotherapy with goserelin; standard chemotherapy with the GnRH agonist goserelin	Drug: goserelin; Gonadotropin-Releasing Hormone Agonist; Other Names: Gonadotropin-Releasing Hormone Agonist; Drug: standard chemotherapy; (Anthracyclines/cyclophosphamide) followed by paclitaxel or doxetaxel; doxetaxel/cyclophosphamide; doxetaxel or paclitaxel/Anthracyclines; fluorouraci/Anthracyclines/cyclophosphamide followed by doxetaxel or paclitaxel; doxetaxel/Anthracyclines/cyclophosphamide; Anthracyclines/cyclophosphamide; Other Names: TAC; AC; TC; TA; AC-P; FAC followed by T
Active Comparator: standard chemotherapy without goserelin	Drug: standard chemotherapy; (Anthracyclines/cyclophosphamide) followed by paclitaxel or doxetaxel; doxetaxel/cyclophosphamide; doxetaxel or paclitaxel/Anthracyclines; fluorouraci/Anthracyclines/cyclophosphamide followed by doxetaxel or paclitaxel; doxetaxel/Anthracyclines/cyclophosphamide; Anthracyclines/cyclophosphamide; Other Names: TAC; AC; TC; TA; AC-P; FAC followed by T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ovarian failure	Ovarian failure is defined as amenorrhea for the preceding 6 months and follicle-stimulating hormone (FSH) and E2 levels in the post -menopausal range 2 year after the end of chemotherapy.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ovarian dysfunction	Ovarian dysfunction is defined as amenorrhea for the preceding 3 months and follicle-stimulating hormone (FSH) and E2 levels in the post -menopausal range 1 year or 2year after the end of chemotherapy.	1 year
Time to the resumption of menstrual activity	Time to the resumption of menstrual activity will be assessed at 3month，1 year and 2year after the end of chemotherapy.	2 year
pregnancy	whether pregnancy will be accessed at 1year, 2year, 3year, 4year, 5year after the end of chemotherapy	5 year
DFS OS	Disease free survival (DFS) and overall survival (OS) will be assessed at 5years after the end of chemotherapy.	5 year
FSH,E2,AMH	FSH, estradiol, and anti-Mullerian hormone (AMH) levels in the postmenopausal range will be assessed at 3month，1 year and 2year after the end of chemotherapy.	2 year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: June 9, 2015
• First Submitted That Met QC Criteria: June 24, 2015
• First Posted (Estimate): June 29, 2015

Study Record Updates

• Last Update Posted (Actual): October 17, 2017
• Last Update Submitted That Met QC Criteria: October 14, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Premenopausal Breast Cancer; Preservation of Ovarian Function; Gonadotropin-Releasing Hormone Agonist
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Goserelin
• Other Study ID Numbers: PUMCH-BC-ovarian suppression