Fertility Preservation in Breast Cancer Patients (Brovale)

January 29, 2025 updated by: Erasme University Hospital

Efficiency and Safety Study of Ovarian Stimulation With Letrozole for Fertility Preservation in Breast Cancer Patients

The purpose of this study is to evaluate efficiency and safety of controlled ovarian stimulation (COS) associated with an aromatase inhibitor (letrozole) for fertility preservation in breast cancer patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients enrolled in this study undergo standard or "random start" ovarian stimulation with Gonadotropins using antagonist protocol before the beginning of chemotherapy. Ovulation is triggered in all patients with a GnRH agonist since amendment P2015/091 (Decapeptyl 0,2mg).

At oocyte retrieval, aspirated follicular fluid is separated from the flush medium for hormonal assays, and oocytes are denuded for ICSI(Intra Cytoplasmic Sperm Injection) or vitrification. Cumulus cells are collected for subsequent analysis of oocyte quality gene expression.

A. Primary objective of the study is to evaluate efficiency of letrozole associated ovarian stimulation for fertility preservation in breast cancer patients in terms of oocyte maturation rate.

Patients' results for primary endpoint are prospectively compared to infertile patients undergoing COS without letrozole.

B. Secondary objectives of the study aim to evaluate safety of the protocol:

  1. Estradiol and progesterone levels at ovulation triggering, ovulation and during luteal phase after oocyte retrieval (days 3 and 8)
  2. The risk of disease relapse will be assessed by long-term follow-up of these patients (up to 5 years) as well as an evaluation of circulating tumoral DNA before and after ovarian stimulation.
  3. Finally obstetrical outcomes will also be recorded.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1070
        • Erasme-CUB

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Breast cancer female patients of less than 41 years old
  • Addressed to fertility preservation Unit before starting chemotherapy

Exclusion Criteria:

  • Metastatic breast cancer
  • Known premature ovarian failure
  • Basal FSH > 20 IU(International Unit)
  • Surgical contra-indications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Letrozole associated COS

Breast cancer patients undergo fertility preservation with letrozole associated COS for oocyte collection.

Letrozole is administered orally (5mg/day) during the entire stimulation protocol until ovulation triggering.
Drug: Letrozole

Patients start ovarian stimulation protocol according to their menstrual cycle phase at enrollment (standard or "random start"). Ovarian stimulation includes gonadotropins administration in a GnRH antagonist protocol Standard Protocol: letrozole is orally administered 2 tablets per day (2,5mgx2/d) from cycle day 2 throughout the ovarian stimulation with gonadotropins protocol until ovulation triggering. GnRH antagonist is administered as soon as at least one follicle reaches 14 mm.

"Random start" protocol: letrozole is administered throughout the stimulation together with gonadotropins and GnRH antagonist, until ovulation triggering.

Oocytes are collected 36h after ovulation triggering. All patients receive GnRH antagonist after oocyte retrieval for 3-7 days or until chemotherapy starts, to induce luteolysis.

Other Names:
  • Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oocyte maturation rate
Time Frame: At oocyte collection (48 hours after last administration of letrozole, following COS protocol).

Following letrozole associated COS, oocytes are collected and evaluated for maturation rate (%).

These results are prospectively compared to infertile patients undergoing similar COS (GnRH antagonist protocol) without letrozole.
At oocyte collection (48 hours after last administration of letrozole, following COS protocol).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hormonal levels
Time Frame: during stimulation at ovulation trigger and oocyte retrieval and during luteal phase (days 3 and 8)
Estradiol and Progesterone levels are measured on serum samples to confirm the effect of COS associated with letrozole on hormonal levels
during stimulation at ovulation trigger and oocyte retrieval and during luteal phase (days 3 and 8)
Circulating tumoral DNA
Time Frame: At enrollment (before letrozole associated COS) and at oocyte retrieval (48 hours after last administration of letrozole, following COS protocol)

3 EDTA (Ethylene Diamine Tetra-Acetic Acid) tubes are collected for plasma extraction. 1 EDTA tube is collected for whole blood.

Circulating tumoral DNA will be assessed on plasma samples according to primary tumoral mutation screening. Whole blood will used as reference.
At enrollment (before letrozole associated COS) and at oocyte retrieval (48 hours after last administration of letrozole, following COS protocol)
Comparison of breast cancer recurrence rate in patients who underwent letrozole associated COS with an oncological control group
Time Frame: 2 and 5 years after letrozole associated COS

Oncological follow-up for relapse risk assessment will be carried out at 2 and 5 years of follow-up by medical chart review. Local, contralateral and/or distant recurrence of the disease will be reported.

These data will be compared to a control group matched for age and type of disease who were diagnosed with breast cancer during the same period but did not undergo letrozole associated COS for fertility preservation.
2 and 5 years after letrozole associated COS
Ovarian reserve
Time Frame: At enrollment, 2 and 5 years after letrozole associated COS for fertility preservation
AMH (anti-mullerian hormone) and FSH (follicle stimulating hormone) are assessed on blood samples to evaluate the gonadotoxicity of chemotherapy.
At enrollment, 2 and 5 years after letrozole associated COS for fertility preservation
Obstetrical outcome: malformation rate
Time Frame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
Malformation will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS): malformation assessment during prenatal morphology ultrasound and/or at birth
Through study completion: data collection at 2 and 5 years after letrozole associated COS
Neonatal outcomes: gestational age at birth
Time Frame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
Neonatal outcomes will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS): gestational age at birth. Preterm delivery is defined by birth < 37 weeks gestation.
Through study completion: data collection at 2 and 5 years after letrozole associated COS
Neonatal outcomes: delivery procedure
Time Frame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
Neonatal outcomes will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS). Delivery procedure is defined as spontaneous, instrumental or cesarean section
Through study completion: data collection at 2 and 5 years after letrozole associated COS
Neonatal outcomes: birth weight
Time Frame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
Neonatal outcomes will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS). Birth weight will be reported in grams.
Through study completion: data collection at 2 and 5 years after letrozole associated COS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Erasme University Hospital

Investigators

  • Principal Investigator: Isabelle Demeestere, Erasme-CUB

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2012

Primary Completion (Actual)

March 1, 2018

Study Completion (Actual)

December 1, 2024

Study Registration Dates

First Submitted

December 23, 2015

First Submitted That Met QC Criteria

January 20, 2016

First Posted (Estimated)

January 25, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 29, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BC-POF 2012

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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