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The study had to be terminated due to the new European legislation on drug studies. This legislation requires all studies aimed at evaluating treatments to be registered as such, even in the context of Standard of Care.
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| Name | Class |
|---|---|
| University Hospital, Lille | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| standard-stimulated cohort | Active Comparator | 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. |
|
| letrozole-stimulated cohort | Experimental | 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. |
|
| non-stimulated cohort | No Intervention | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Letrozole | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Characteristics of Ovarian stimulation: total gonadotropin doses |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Isabelle Demeestere, MD, PhD | CUB-Hôpital Erasme | Study Director |
| Matteo Lambertini, MD, PhD | ULB | Study Chair |
| Christine Decanter, MD | CHRU LILLE | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CUB-Hôpital Erasme | Brussels | 1070 | Belgium | |||
| CHIREC- Hospital Delta |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 10, 2018 | Feb 25, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000077289 | Letrozole |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 |
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3 groups:
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|
| standard-stimulated cohort | Other | 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. |
|
|
Total gonadotropin doses (International Unit- IU) |
| An average of 2 weeks after inclusion |
| Characteristics of Ovarian stimulation: duration of the COS | duration of the COS (days) | An average of 2 weeks after inclusion |
| Characteristics of Ovarian stimulation: type of stimulation | type of stimulation (standard or random-start). | An average of 2 weeks after inclusion |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Anticancer therapies effect on ovarian function | Amenorrhea rate (6months without spontaneous menstruation) | An average 18 months, 30 months, 60 months after inclusion |
| Oncological outcomes 1 | Invasive disease-free survival (iDFS) | 5 years |
| Oncological outcomes 2 | breast cancer-free interval (BCFI) | 5 years |
| Oncological outcomes 3 | overall survival (OS) | 5 years |
| Circulating breast cancer cells level before stimulation | circulating tumor DNA (ctDNA) | Inclusion |
| Circulating breast cancer cells level after stimulation | circulating tumor DNA (ctDNA) | average of 2weeks after inclusion |
| Number of patient with adverse events due to egg collection | bleeding | An average of 2 weeks after inclusion |
| Number of patient with adverse events due to egg collection | pelvic infection | An average of 2 weeks after inclusion |
| Efficacy of the in vitro fertilization procedure: Fertilization rate | Fertilization rate (number of oocyte fertilized/number of embryo obtained) | Through study completion, 5 years |
| Brussels |
| 1160 |
| Belgium |
| CHC-Saint Vincent | Liège | 4000 | Belgium |
| Centre Oscar Lambret | Lille | 59000 | France |
| CHRU Lille | Lille | 59037 | France |
| Ospedale San Martino | Genova | 16132 | Italy |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |