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

Breast Neoplasm Malignant Female Clinical Trial

— fAMHOPE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04289805
• Other study ID #: SRB_201808_163
• Status: Recruiting
• Phase: Phase 4
• Start date: February 25, 2019
• Est. completion date: January 30, 2029

Study information

• Verified date: August 2022
• Source: Erasme University Hospital
• Contact: Isabelle Demeestere, MD,PhD
• Phone: 003225556592
• Email: isabelle.demeestere[@]ulb.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 565
• Est. completion date: January 30, 2029
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasm Malignant Female
• Breast Neoplasms
• Neoplasms

Intervention

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:
• 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.

Locations

Country	Name	City	State
Belgium	CHIREC- Hospital Delta	Brussel
Belgium	CUB-Hôpital Erasme	Brussel
Belgium	CHC-Saint Vincent	Liège
France	Centre Oscar Lambret	Lille
France	CHRU Lille	Lille
Italy	Ospedale San Martino	Genova

Sponsors (2)

Lead Sponsor	Collaborator
Erasme University Hospital	University Hospital, Lille

Countries where clinical trial is conducted

Belgium,  France,  Italy, 

Outcome

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