Controlled Ovarian Stimulation in Newly Diagnosed Breast Cancer PatiEnts (fAMHOPE) (fAMHOPE)

January 29, 2025 updated by: Erasme University Hospital

A Multicenter Prospective coHort Study of Controlled Ovarian Stimulation in Newly Diagnosed Breast Cancer PatiEnts (fAMHOPE)

This is a multicenter hospital-based prospective cohort study conducted in institutions with known expertise in performing oocytes/embryo freezing for fertility preservation. The study aims at refining the understanding of the efficacy and safety of controlled ovarian stimulation with or without letrozole in young women with newly diagnosed breast cancer who are candidates to receive (neo)adjuvant chemotherapy.

Study Overview

Status

Terminated

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 Gonadotropin Releasing Hormone-GnRH agonist.

After retrieval, oocytes are denuded and matured oocytes are subjected to fertilization before embryo freezing or direct vitrification.

Primary objective is to evaluate the efficacy of performing a controlled ovarian stimulation with or without letrozole in young women with newly diagnosed breast cancer who are candidates to receive (neo)adjuvant chemotherapy in terms of mature oocytes collected.

Study Type

Interventional

Enrollment (Actual)

96

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
      • Brussel, Belgium, 1070
        • CUB-Hôpital Erasme
      • Brussel, Belgium, 1160
        • CHIREC- Hospital Delta
      • Liège, Belgium, 4000
        • CHC-Saint Vincent
  • France
      • Lille, France, 59000
        • Centre Oscar Lambret
      • Lille, France, 59037
        • Chru Lille
  • Italy
      • Genova, Italy, 16132
        • Ospedale San Martino

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:

  • Diagnosis of invasive non-metastatic breast cancer (i.e. stage I to III);
  • Breast cancer diagnosis ≥18 and ≤ 40 years;
  • No prior history of gonadotoxic treatments;
  • Fertility preservation counseling for fertility preservation;
  • Written inform consent;
  • FSH < 20 UI/L and/or antra-follicular count ≥ 6 (follicles of 2-9 mm) and/or AMH ≥ 6 pmol (only applicable for patients who undergo controlled ovarian stimulation for embryo/oocyte cryopreservation).

Exclusion Criteria:

  • Newly diagnosed stage IV breast cancer (i.e. de novo metastatic breast cancer);
  • Prior diagnosis of other malignancies before breast cancer.

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: standard-stimulated cohort
this cohort includes all newly diagnosed breast cancer patients who are candidates to receive (neo)adjuvant chemotherapy and wish to preserve their fertility by undergoing oocyte/embryo cryopreservation at the French participating centres.
Other: standard-stimulated cohort

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": Gonadotrophins started from cycle day 2-3 throughout the ovarian stimulation until ovulation triggering.

"Random start" protocol: Gonadotrophins started at any time of the cycle and throughout the stimulation.

GnRH antagonist is administered at cycle day 7 or as soon as at least one follicle reaches 12-14 mm.

Oocytes are collected 36h after ovulation triggering with GnRH agonist.

Other Names:
  • COS
Experimental: letrozole-stimulated cohort
this cohort includes all newly diagnosed breast cancer patients who are candidates to receive (neo)adjuvant chemotherapy and wish to preserve their fertility by undergoing oocyte/embryo cryopreservation at the Belgian participating centres.
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 (5mg/d) from cycle day 2-3 throughout the ovarian stimulation with gonadotropins protocol until ovulation triggering.

"Random start" protocol: letrozole is administered throughout the stimulation together with gonadotropins.

GnRH antagonist is administered at cycle day 7 or as soon as at least one follicle reaches 12-14 mm.

Oocytes are collected 36h after ovulation triggering with GnRH agonist.

Other Names:
  • Controlled Ovarian Stimulation (COS)
No Intervention: non-stimulated cohort
this cohort includes all newly diagnosed breast cancer patients who are candidates to receive (neo)adjuvant chemotherapy and who have access to the Fertility Clinics in all the participating centres but are not willing to preserve their fertility by undergoing oocyte/embryo cryopreservation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of the ovarian stimulation and oocyte collection procedure: Number of mature oocytes collected
Time Frame: an average of 2 weeks after inclusion
Number of mature oocytes collected
an average of 2 weeks after inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patient with adverse events due to COS: OHSS
Time Frame: Through treatment procedure, an average of 2 weeks after inclusion
Adverse events reporting during COS (Ovarian Hyperstimulation syndrome-OHSS)
Through treatment procedure, an average of 2 weeks after inclusion
Characteristics of Ovarian stimulation: total gonadotropin doses
Time Frame: An average of 2 weeks after inclusion
Total gonadotropin doses (International Unit- IU)
An average of 2 weeks after inclusion
Characteristics of Ovarian stimulation: duration of the COS
Time Frame: An average of 2 weeks after inclusion
duration of the COS (days)
An average of 2 weeks after inclusion
Characteristics of Ovarian stimulation: type of stimulation
Time Frame: An average of 2 weeks after inclusion
type of stimulation (standard or random-start).
An average of 2 weeks after inclusion
Efficacy of the ovarian stimulation and oocyte collection: Maturation rate
Time Frame: An average of 2 weeks after inclusion
Maturation rate (number of total oocyte collected/number of mature oocytes)
An average of 2 weeks after inclusion
Outcomes of assisted reproductive technology procedures
Time Frame: Through study completion, 5 years
Number of pregnancies and outcomes (premature delivery, miscarriage, abortion, delivery healthy babies, congenital malformation).
Through study completion, 5 years
Anticancer therapies effect on ovarian function: progesterone
Time Frame: Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Hormonal measurements Progesterone ng/ml
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function: AMH
Time Frame: Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anti-Mullerian Hormone (AMH) measurements AMH ng/ml
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function: FSH
Time Frame: Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Follicle-Stimulating Hormone (FSH) measurements FSH IU/L
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function: E2
Time Frame: Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Hormonal measurements E2 pg/ml
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function
Time Frame: An average 18 months, 30 months, 60 months after inclusion
Amenorrhea rate (6months without spontaneous menstruation)
An average 18 months, 30 months, 60 months after inclusion
Oncological outcomes 1
Time Frame: 5 years
Invasive disease-free survival (iDFS)
5 years
Oncological outcomes 2
Time Frame: 5 years
breast cancer-free interval (BCFI)
5 years
Oncological outcomes 3
Time Frame: 5 years
overall survival (OS)
5 years
Circulating breast cancer cells level before stimulation
Time Frame: Inclusion
circulating tumor DNA (ctDNA)
Inclusion
Circulating breast cancer cells level after stimulation
Time Frame: average of 2weeks after inclusion
circulating tumor DNA (ctDNA)
average of 2weeks after inclusion
Number of patient with adverse events due to egg collection
Time Frame: An average of 2 weeks after inclusion
bleeding
An average of 2 weeks after inclusion
Number of patient with adverse events due to egg collection
Time Frame: An average of 2 weeks after inclusion
pelvic infection
An average of 2 weeks after inclusion
Efficacy of the in vitro fertilization procedure: Fertilization rate
Time Frame: Through study completion, 5 years
Fertilization rate (number of oocyte fertilized/number of embryo obtained)
Through study completion, 5 years

Collaborators and Investigators

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

Sponsor

Erasme University Hospital

Collaborators

University Hospital, Lille

Investigators

  • Study Chair: Christine DECANTER, MD, Chru Lille
  • Study Director: Isabelle Demeestere, MD, PhD, CUB-Hôpital Erasme
  • Study Chair: Matteo Lambertini, MD, PhD, ULB

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)

February 25, 2019

Primary Completion (Actual)

January 15, 2025

Study Completion (Actual)

January 15, 2025

Study Registration Dates

First Submitted

July 17, 2019

First Submitted That Met QC Criteria

February 26, 2020

First Posted (Actual)

February 28, 2020

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

  • SRB_201808_163

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

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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