search
Back to results

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

Primary Purpose

Breast Neoplasm Malignant Female

Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Letrozole
standard-stimulated cohort
Sponsored by
Erasme University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Neoplasm Malignant Female focused on measuring Fertility preservation, Letrozole, Ovarian stimulation

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • CUB-Hôpital ErasmeRecruiting
  • CHIREC- Hospital Delta
  • CHC-Saint VincentRecruiting
  • Centre Oscar LambretRecruiting
  • CHRU LilleRecruiting
  • Ospedale San Martino

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

No Intervention

Arm Label

standard-stimulated cohort

letrozole-stimulated cohort

non-stimulated cohort

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Efficacy of the ovarian stimulation and oocyte collection procedure: Number of mature oocytes collected
Number of mature oocytes collected

Secondary Outcome Measures

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

Full Information

First Posted
July 17, 2019
Last Updated
August 2, 2022
Sponsor
Erasme University Hospital
Collaborators
University Hospital, Lille
search

1. Study Identification

Unique Protocol Identification Number
NCT04289805
Brief Title
Controlled Ovarian Stimulation in Newly Diagnosed Breast Cancer PatiEnts (fAMHOPE)
Acronym
fAMHOPE
Official Title
A Multicenter Prospective coHort Study of Controlled Ovarian Stimulation in Newly Diagnosed Breast Cancer PatiEnts (fAMHOPE)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 25, 2019 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
January 30, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Erasme University Hospital
Collaborators
University Hospital, Lille

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasm Malignant Female
Keywords
Fertility preservation, Letrozole, Ovarian stimulation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
565 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
standard-stimulated cohort
Arm Type
Active Comparator
Arm Description
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.
Arm Title
letrozole-stimulated cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
non-stimulated cohort
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Letrozole
Other Intervention Name(s)
Controlled Ovarian Stimulation (COS)
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
standard-stimulated cohort
Other Intervention Name(s)
COS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Efficacy of the ovarian stimulation and oocyte collection procedure: Number of mature oocytes collected
Description
Number of mature oocytes collected
Time Frame
an average of 2 weeks after inclusion
Secondary Outcome Measure Information:
Title
Number of patient with adverse events due to COS: OHSS
Description
Adverse events reporting during COS (Ovarian Hyperstimulation syndrome-OHSS)
Time Frame
Through treatment procedure, an average of 2 weeks after inclusion
Title
Characteristics of Ovarian stimulation: total gonadotropin doses
Description
Total gonadotropin doses (International Unit- IU)
Time Frame
An average of 2 weeks after inclusion
Title
Characteristics of Ovarian stimulation: duration of the COS
Description
duration of the COS (days)
Time Frame
An average of 2 weeks after inclusion
Title
Characteristics of Ovarian stimulation: type of stimulation
Description
type of stimulation (standard or random-start).
Time Frame
An average of 2 weeks after inclusion
Title
Efficacy of the ovarian stimulation and oocyte collection: Maturation rate
Description
Maturation rate (number of total oocyte collected/number of mature oocytes)
Time Frame
An average of 2 weeks after inclusion
Title
Outcomes of assisted reproductive technology procedures
Description
Number of pregnancies and outcomes (premature delivery, miscarriage, abortion, delivery healthy babies, congenital malformation).
Time Frame
Through study completion, 5 years
Title
Anticancer therapies effect on ovarian function: progesterone
Description
Hormonal measurements Progesterone ng/ml
Time Frame
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Title
Anticancer therapies effect on ovarian function: AMH
Description
Anti-Mullerian Hormone (AMH) measurements AMH ng/ml
Time Frame
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Title
Anticancer therapies effect on ovarian function: FSH
Description
Follicle-Stimulating Hormone (FSH) measurements FSH IU/L
Time Frame
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Title
Anticancer therapies effect on ovarian function: E2
Description
Hormonal measurements E2 pg/ml
Time Frame
Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Title
Anticancer therapies effect on ovarian function
Description
Amenorrhea rate (6months without spontaneous menstruation)
Time Frame
An average 18 months, 30 months, 60 months after inclusion
Title
Oncological outcomes 1
Description
Invasive disease-free survival (iDFS)
Time Frame
5 years
Title
Oncological outcomes 2
Description
breast cancer-free interval (BCFI)
Time Frame
5 years
Title
Oncological outcomes 3
Description
overall survival (OS)
Time Frame
5 years
Title
Circulating breast cancer cells level before stimulation
Description
circulating tumor DNA (ctDNA)
Time Frame
Inclusion
Title
Circulating breast cancer cells level after stimulation
Description
circulating tumor DNA (ctDNA)
Time Frame
average of 2weeks after inclusion
Title
Number of patient with adverse events due to egg collection
Description
bleeding
Time Frame
An average of 2 weeks after inclusion
Title
Number of patient with adverse events due to egg collection
Description
pelvic infection
Time Frame
An average of 2 weeks after inclusion
Title
Efficacy of the in vitro fertilization procedure: Fertilization rate
Description
Fertilization rate (number of oocyte fertilized/number of embryo obtained)
Time Frame
Through study completion, 5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Isabelle Demeestere, MD,PhD
Phone
003225556592
Email
isabelle.demeestere@ulb.be
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Dechene
Phone
003225556779
Email
julie.dechene@ulb.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Isabelle Demeestere, MD, PhD
Organizational Affiliation
CUB-Hôpital Erasme
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Matteo Lambertini, MD, PhD
Organizational Affiliation
ULB
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Christine Decanter, MD
Organizational Affiliation
CHRU Lille
Official's Role
Study Chair
Facility Information:
Facility Name
CUB-Hôpital Erasme
City
Brussel
ZIP/Postal Code
1070
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Dechène
Phone
00 32 2 555 67 79
Email
julie.dechene@ulb.be
First Name & Middle Initial & Last Name & Degree
Lydia Ait Ahcene
Phone
0032 2 555 69 26
Email
lydia.ait.ahcene@erasme.ulb.ac.be
First Name & Middle Initial & Last Name & Degree
Oranite Goldrat, Md, PhD
Facility Name
CHIREC- Hospital Delta
City
Brussel
ZIP/Postal Code
1160
Country
Belgium
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain Imbert, MD
First Name & Middle Initial & Last Name & Degree
Romain Imbert, MD
Facility Name
CHC-Saint Vincent
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chantal Schugens
Phone
0032 4 355 42 73
Email
chantal.schugens@chc.be
First Name & Middle Initial & Last Name & Degree
Carine Garnier
Phone
0032 4 355 42 50
Email
carine.garnier@chc.be
First Name & Middle Initial & Last Name & Degree
Annick Delvigne, MD, PhD
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aline BARBERIO
Phone
0033 3 20 29 56 15
Email
a-barberio@o-lambret.fr
First Name & Middle Initial & Last Name & Degree
audrey Mailliez, MD
Facility Name
CHRU Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Decanter, MD
First Name & Middle Initial & Last Name & Degree
Christine Decanter, MD
Facility Name
Ospedale San Martino
City
Genova
ZIP/Postal Code
16132
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matteo Lambertini, MD, PhD
First Name & Middle Initial & Last Name & Degree
Matteo Lambertini, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs