Clinical trial NCT02661932: Fertility Preservation in Breast Cancer Patients
Official title: Efficiency and Safety Study of Ovarian Stimulation With Letrozole for Fertility Preservation in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Breast Neoplasms
Fertility
Keywords: Fertility preservation
letrozole
Ovarian stimulation
Lead sponsor: Erasme University Hospital
Sponsor class: OTHER
First posted: 2016-01-25
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Oocyte maturation rate
timeFrame: At oocyte collection (48 hours after last administration of letrozole, following COS protocol).
Secondary outcomes:
measure: Hormonal levels
timeFrame: during stimulation at ovulation trigger and oocyte retrieval and during luteal phase (days 3 and 8)
measure: Circulating tumoral DNA
timeFrame: At enrollment (before letrozole associated COS) and at oocyte retrieval (48 hours after last administration of letrozole, following COS protocol)
measure: Comparison of breast cancer recurrence rate in patients who underwent letrozole associated COS with an oncological control group
timeFrame: 2 and 5 years after letrozole associated COS
measure: Ovarian reserve
timeFrame: At enrollment, 2 and 5 years after letrozole associated COS for fertility preservation
measure: Obstetrical outcome: malformation rate
timeFrame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
measure: Neonatal outcomes: gestational age at birth
timeFrame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
measure: Neonatal outcomes: delivery procedure
timeFrame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
measure: Neonatal outcomes: birth weight
timeFrame: Through study completion: data collection at 2 and 5 years after letrozole associated COS
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Erasme-CUB
Study officials:
affiliation: Erasme-CUB
name: Isabelle Demeestere
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goldrat O, De Cooman M, Mailliez A, Delbaere A, D'Orazio E, Demeestere I, Decanter C. Efficacy and safety of controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: A multicenter retrospective study. Eur J Cancer. 2022 Oct;174:134-141. doi: 10.1016/j.ejca.2022.07.017. Epub 2022 Aug 20.
citation: Goldrat O, Delbaere A, Demeestere I. Impact of letrozole-associated controlled ovarian hyperstimulation on ART outcomes and endocrinological parameters. Hum Reprod. 2022 Oct 31;37(11):2722-2723. doi: 10.1093/humrep/deac206. No abstract available.
citation: Goldrat O, Gervy C, Englert Y, Delbaere A, Demeestere I. Progesterone levels in letrozole associated controlled ovarian stimulation for fertility preservation in breast cancer patients. Hum Reprod. 2015 Sep;30(9):2184-9. doi: 10.1093/humrep/dev155. Epub 2015 Jun 24.
citation: Goldrat O, Van Den Steen G, Gonzalez-Merino E, Dechene J, Gervy C, Delbaere A, Devreker F, De Maertelaer V, Demeestere I. Letrozole-associated controlled ovarian hyperstimulation in breast cancer patients versus conventional controlled ovarian hyperstimulation in infertile patients: assessment of oocyte quality related biomarkers. Reprod Biol Endocrinol. 2019 Jan 3;17(1):3. doi: 10.1186/s12958-018-0443-x.