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

Sponsor
Erasme University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04289805
Collaborator
University Hospital, Lille (Other)
565
Enrollment
6
Locations
3
Arms
119.2
Anticipated Duration (Months)
94.2
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
565 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
3 groups: 113 patients in the standard-stimulated cohort, 113 patients in the letrozole-stimulated cohort, 339 patients in the non-stimulated cohort.3 groups: 113 patients in the standard-stimulated cohort, 113 patients in the letrozole-stimulated cohort, 339 patients in the non-stimulated cohort.
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
A Multicenter Prospective coHort Study of Controlled Ovarian Stimulation in Newly Diagnosed Breast Cancer PatiEnts (fAMHOPE)
Actual Study Start Date :
Feb 25, 2019
Anticipated Primary Completion Date :
Dec 30, 2023
Anticipated Study Completion Date :
Jan 30, 2029

Arms and Interventions

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.

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy of the ovarian stimulation and oocyte collection procedure: Number of mature oocytes collected [an average of 2 weeks after inclusion]

      Number of mature oocytes collected

    Secondary Outcome Measures

    1. Number of patient with adverse events due to COS: OHSS [Through treatment procedure, an average of 2 weeks after inclusion]

      Adverse events reporting during COS (Ovarian Hyperstimulation syndrome-OHSS)

    2. Characteristics of Ovarian stimulation: total gonadotropin doses [An average of 2 weeks after inclusion]

      Total gonadotropin doses (International Unit- IU)

    3. Characteristics of Ovarian stimulation: duration of the COS [An average of 2 weeks after inclusion]

      duration of the COS (days)

    4. Characteristics of Ovarian stimulation: type of stimulation [An average of 2 weeks after inclusion]

      type of stimulation (standard or random-start).

    5. Efficacy of the ovarian stimulation and oocyte collection: Maturation rate [An average of 2 weeks after inclusion]

      Maturation rate (number of total oocyte collected/number of mature oocytes)

    6. Outcomes of assisted reproductive technology procedures [Through study completion, 5 years]

      Number of pregnancies and outcomes (premature delivery, miscarriage, abortion, delivery healthy babies, congenital malformation).

    7. Anticancer therapies effect on ovarian function: progesterone [Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months]

      Hormonal measurements Progesterone ng/ml

    8. Anticancer therapies effect on ovarian function: AMH [Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months]

      Anti-Mullerian Hormone (AMH) measurements AMH ng/ml

    9. Anticancer therapies effect on ovarian function: FSH [Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months]

      Follicle-Stimulating Hormone (FSH) measurements FSH IU/L

    10. Anticancer therapies effect on ovarian function: E2 [Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months]

      Hormonal measurements E2 pg/ml

    11. Anticancer therapies effect on ovarian function [An average 18 months, 30 months, 60 months after inclusion]

      Amenorrhea rate (6months without spontaneous menstruation)

    12. Oncological outcomes 1 [5 years]

      Invasive disease-free survival (iDFS)

    13. Oncological outcomes 2 [5 years]

      breast cancer-free interval (BCFI)

    14. Oncological outcomes 3 [5 years]

      overall survival (OS)

    15. Circulating breast cancer cells level before stimulation [Inclusion]

      circulating tumor DNA (ctDNA)

    16. Circulating breast cancer cells level after stimulation [average of 2weeks after inclusion]

      circulating tumor DNA (ctDNA)

    17. Number of patient with adverse events due to egg collection [An average of 2 weeks after inclusion]

      bleeding

    18. Number of patient with adverse events due to egg collection [An average of 2 weeks after inclusion]

      pelvic infection

    19. Efficacy of the in vitro fertilization procedure: Fertilization rate [Through study completion, 5 years]

      Fertilization rate (number of oocyte fertilized/number of embryo obtained)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 40 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CUB-Hôpital Erasme Brussel Belgium 1070
    2 CHIREC- Hospital Delta Brussel Belgium 1160
    3 CHC-Saint Vincent Liège Belgium 4000
    4 Centre Oscar Lambret Lille France 59000
    5 CHRU Lille Lille France 59037
    6 Ospedale San Martino Genova Italy 16132

    Sponsors and Collaborators

    • Erasme University Hospital
    • University Hospital, Lille

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Erasme University Hospital
    ClinicalTrials.gov Identifier:
    NCT04289805
    Other Study ID Numbers:
    • SRB_201808_163
    First Posted:
    Feb 28, 2020
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Erasme University Hospital
    Fertility preservation
    Letrozole
    Ovarian stimulation
    Additional relevant MeSH terms:
    Breast Neoplasms
    Neoplasms
    Letrozole

    Study Results

    No Results Posted as of Aug 4, 2022