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Completed

NCT Number: NCT02661932

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.

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Key information

Conditions

Breast Neoplasms Breast Diseases Fertility Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Erasme-CUB

Brussels, 1070, Belgium

About this study

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:

  • Estradiol and progesterone levels at ovulation triggering, ovulation and during luteal phase after oocyte retrieval (days 3 and 8)
  • 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.
  • Finally obstetrical outcomes will also be recorded.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

letrozole

Drug

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

Sponsors and collaborators

Lead sponsor

Erasme University Hospital

Other

Registry information

Official study title

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

Acronym: Brovale

Important dates

Study start
2012
Primary completion
2018
Study completion
2024
First posted
Jan 25, 2016
Registry last updated
Jan 31, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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