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AzTrials

Breast NeoplasmsPhase 4BrovaleNCT02661932

Fertility Preservation in Breast Cancer Patients

A Phase 4 study testing Letrozole in people with Breast Neoplasms and Fertility, run by Erasme University Hospital at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 40 years, women only
Conditions the study is for
Breast Neoplasms, Fertility
What is being tested?
Letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
1 siteBelgium
Study dates
Nov 2012to Dec 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Erasme-CUB

    Brussels, 1070

Other trials in Belgium

About this study

Official title: 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.

Read the 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.

  1. 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.

  1. Secondary objectives of the study aim to evaluate safety of the protocol:
  2. Estradiol and progesterone levels at ovulation triggering, ovulation and during luteal phase after oocyte retrieval (days 3 and 8)
  3. 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.
  4. Finally obstetrical outcomes will also be recorded.
Being tested
Letrozole
Keywords
Fertility preservation, letrozole, Ovarian stimulation
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LetrozoleDrug

    Also called Femara

    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.

Study groups in NCT02661932
Study groupRoleWhat they receive
Letrozole associated COSExperimentalBreast 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.
Receives: Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Oocyte maturation rate

    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.

    Measured: At oocyte collection (48 hours after last administration of letrozole, following COS protocol).

Secondary outcomes (8)

  1. Hormonal levels

    Estradiol and Progesterone levels are measured on serum samples to confirm the effect of COS associated with letrozole on hormonal levels

    Measured: during stimulation at ovulation trigger and oocyte retrieval and during luteal phase (days 3 and 8)

  2. Circulating tumoral DNA

    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.

    Measured: At enrollment (before letrozole associated COS) and at oocyte retrieval (48 hours after last administration of letrozole, following COS protocol)

  3. Comparison of breast cancer recurrence rate in patients who underwent letrozole associated COS with an oncological control group

    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.

    Measured: 2 and 5 years after letrozole associated COS

  4. Ovarian reserve

    AMH (anti-mullerian hormone) and FSH (follicle stimulating hormone) are assessed on blood samples to evaluate the gonadotoxicity of chemotherapy.

    Measured: At enrollment, 2 and 5 years after letrozole associated COS for fertility preservation

  5. Obstetrical outcome: malformation rate

    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

    Measured: Through study completion: data collection at 2 and 5 years after letrozole associated COS

  6. Neonatal outcomes: gestational age at birth

    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.

    Measured: Through study completion: data collection at 2 and 5 years after letrozole associated COS

  7. Neonatal outcomes: delivery procedure

    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

    Measured: Through study completion: data collection at 2 and 5 years after letrozole associated COS

  8. Neonatal outcomes: birth weight

    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.

    Measured: Through study completion: data collection at 2 and 5 years after letrozole associated COS

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2016 (estimated)
  2. Study startNov 2012
  3. Primary completionMar 2018
  4. Study completionDec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02661932
Sponsor's protocol ID
BC-POF 2012
Acronym
Brovale
Status last verified
Dec 2024
First submitted
23 Dec 2015
Last updated
31 Jan 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35998549

  • 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.

    PubMed 36124889

  • 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.

    PubMed 26109617

  • 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.

    PubMed 30606204

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Letrozole in people with Breast Neoplasms and Fertility, run by Erasme University Hospital at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Oocyte maturation rate (time frame: At oocyte collection (48 hours after last administration of letrozole, following COS protocol).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02661932, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.

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