Goserelin for Ovarian Protection in Premenopausal Patients Receiving Cyclophosphamide

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

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.

Study Overview

• Status: Unknown
• Conditions: Ovarian Failure
• Intervention / Treatment: Drug: Goserelin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: chemotherapy without goserelin; these patients will receive their chemotherapy without addition of Goserelin
EXPERIMENTAL: chemotherapy with goserelin; these patients will receive their chemotherapy with addition of Goserelin	Drug: Goserelin; adding goserelin with chemotherapy; Other Names: zoladex

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Chair: samir Eid, phd, Assiut University

Publications and helpful links

General Publications

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012 Feb 4;379(9814):432-44. doi: 10.1016/S0140-6736(11)61625-5. Epub 2011 Dec 5.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2018
• Primary Completion (ANTICIPATED): March 1, 2020
• Study Completion (ANTICIPATED): March 1, 2020

Study Registration Dates

• First Submitted: March 11, 2018
• First Submitted That Met QC Criteria: March 17, 2018
• First Posted (ACTUAL): March 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2018
• Last Update Submitted That Met QC Criteria: March 17, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Goserelin
• Other Study ID Numbers: GOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No