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

Phase 4
Terminated
Conditions
Breast Neoplasm Malignant Female
Interventions
Other: standard-stimulated cohort
Registration Number
NCT04289805
Lead Sponsor
Erasme University Hospital
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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
96
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
standard-stimulated cohortstandard-stimulated cohortthis 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.
letrozole-stimulated cohortLetrozolethis 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.
Primary Outcome Measures
NameTimeMethod
Efficacy of the ovarian stimulation and oocyte collection procedure: Number of mature oocytes collectedan average of 2 weeks after inclusion

Number of mature oocytes collected

Secondary Outcome Measures
NameTimeMethod
Efficacy of the ovarian stimulation and oocyte collection: Maturation rateAn average of 2 weeks after inclusion

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

Anticancer therapies effect on ovarian function: FSHInclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months

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

Characteristics of Ovarian stimulation: duration of the COSAn average of 2 weeks after inclusion

duration of the COS (days)

Characteristics of Ovarian stimulation: type of stimulationAn average of 2 weeks after inclusion

type of stimulation (standard or random-start).

Number of patient with adverse events due to COS: OHSSThrough treatment procedure, an average of 2 weeks after inclusion

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

Circulating breast cancer cells level after stimulationaverage of 2weeks after inclusion

circulating tumor DNA (ctDNA)

Number of patient with adverse events due to egg collectionAn average of 2 weeks after inclusion

pelvic infection

Anticancer therapies effect on ovarian function: AMHInclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months

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

Oncological outcomes 15 years

Invasive disease-free survival (iDFS)

Efficacy of the in vitro fertilization procedure: Fertilization rateThrough study completion, 5 years

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

Characteristics of Ovarian stimulation: total gonadotropin dosesAn average of 2 weeks after inclusion

Total gonadotropin doses (International Unit- IU)

Anticancer therapies effect on ovarian functionAn average 18 months, 30 months, 60 months after inclusion

Amenorrhea rate (6months without spontaneous menstruation)

Oncological outcomes 25 years

breast cancer-free interval (BCFI)

Outcomes of assisted reproductive technology proceduresThrough study completion, 5 years

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

Anticancer therapies effect on ovarian function: progesteroneInclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months

Hormonal measurements Progesterone ng/ml

Anticancer therapies effect on ovarian function: E2Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months

Hormonal measurements E2 pg/ml

Oncological outcomes 35 years

overall survival (OS)

Circulating breast cancer cells level before stimulationInclusion

circulating tumor DNA (ctDNA)

Trial Locations

Locations (6)

CUB-Hôpital Erasme

🇧🇪

Brussel, Belgium

CHIREC- Hospital Delta

🇧🇪

Brussel, Belgium

CHC-Saint Vincent

🇧🇪

Liège, Belgium

Centre Oscar Lambret

🇫🇷

Lille, France

CHRU Lille

🇫🇷

Lille, France

Ospedale San Martino

🇮🇹

Genova, Italy

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