Risk of Infertility Related to Adjuvant Chemotherapy in Young Breast Cancer Patients: Oocyte/Embryo Cryopreservation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Oscar Lambret

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Dec 2016 → ongoing

Decision date (initial)

2024-06-26

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513078-23-00

EudraCT number

2016-000808-28

ClinicalTrials.gov

NCT02871167

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate efficiency of oocyte or embryo cryopreservation after controlled ovarian stimulation in young breast cancer patients who will receive adjuvant chemotherapy, in particular in terms of numbers of Meta II oocytes that can be vitrified

Secondary objectives 9

1. To evaluate among young breast cancer patients who will receive adjuvant chemotherapy the proportion of those with sufficient ovarian reserve eligible for the controlled ovarian hyperstimulation
2. To evaluate the toxicity of controlled ovarian hyperstimulation, in particular the risk of ovarian hyperstimulation syndrome (OHSS) requiring an additional medical visit or a hospitalization, and the risk of vascular complication (thrombosis)
3. To evaluate the impact of the fertility preservation program on the schedule of anti cancer treatment
4. To evaluate the gonadotoxicty of chemotherapy in terms of: - AMH level and AFC over time, - incidence and duration of chemotherapy-induced amenorrhea, premature ovarian failure and chemotherapy-induced definitive menopause
5. To evaluate the fertility and fecundity, in terms the cumulative incidence of pregnancy and live birth and estimate the cumulative number of pregnancies and live births among all patients who started the controlled ovarian hyperstimulation, and to describe the type of pregnancy (spontaneous versus assisted pregnancy without or with frozen gametes) and the pregnancy outcome (miscarriage or live birth, single or multiple)
6. To measure the degree of project completion of subsequent pregnancy(ies) in terms of cumulative incidence of pregnancy and live birth, and cumulative number of pregnancies and live births in patients who started the controlled ovarian hyperstimulation and who expressed the wish to be pregnant
7. To assess the number of patients wishing for re-utilization of their frozen gametes
8. To evaluate the long-term safety of the procedure in terms of the risk of relapse compared to historical controls
9. EXPLORATORY OBJECTIVES (TRANSLATIONAL RESEARCH) : To identify new non-invasive biomarkers of follicle/oocyte quality based on miRNA and cfDNA in patients undergoing controlled ovarian hyperstimulation.

Conditions and MedDRA coding

breast cancer in young women

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Women with newly diagnosed histological proven breast cancer (whatever the grade, size, nodal status, histological type, HR and HER2 status)
2. Aged from 18 to 38 years old
3. Planned adjuvant chemotherapy Standard sequential anthracycline and taxane based chemotherapy (according to local practices) +/- Trastuzumab +/- Hormonotherapy
4. No prior chemotherapy
5. Affiliated to a public health insurance program
6. Signed informed consent form
7. ADDITIONAL ELIGIBILITY CRITERIA FOR COH : Sufficient ovarian reserve (i-e AMH≥ 6 pmol/l or AFC ≥ 6 follicles)

Exclusion criteria 8

1. Metastatic breast cancer
2. Planned neo-adjuvant chemotherapy
3. Hysterectomy
4. Exclusive adjuvant hormonotherapy
5. Positive serology for syphilis, hepatitis B or C, or VIH
6. Contraindication related to use of r-FSH: primary gonadal failure (primary amenorrhea), ovarian tumor, tumor of the uterus , pituitary or hypothalamus , vaginal bleeding cause undetermined , ovarian cysts or enlarged ovaries, not related to polycystic ovary syndrome, malformation of genitalia incompatible with pregnancy, uterine myomas incompatible with pregnancy
7. Pregnant or breastfeeding patients
8. Unable for medical follow-up (geographic, social or mental reasons)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Quality of the oocyte retrieval will be evaluated in terms of numbers of Meta II oocytes that can be vitrified

Secondary endpoints 8

1. Quality of oocyte and embryo retrieval will also be evaluated in terms of: • Total number of embryos and oocytes preserved • Rate of top quality embryos • Number of mature, immature and atretic oocytes
2. The ovarian reserve at study entry will be described in terms of AMH level and Antral Follicle Count (AFC). A patient will be classified as eligible for the controlled ovarian stimulation (second part of the study) if the ovarian reserve is sufficient, defined as AMH≥ 6 pmol/l or AFC ≥ 6 follicles.
3. Safety of the study procedures shall be evaluated over the month following the egg retrieval and judged on the NCI-CTCAE scale, version 4.0, and in terms of suggestive clinical, ultrasound and/or biological signs requiring at least an additional visit to the reproductive medicine center.Hyperstimulation syndrome (OHSS) will be graded according to Delvigne criteria. after the end of standard chemotherapy adverse events related to the study procedures will be reported.
4. The impact of the fertility preservation program on the schedule of anti-cancer treatment will be evaluated in terms of the time interval between surgery and the start of chemotherapy. A delayed start of chemotherapy is defined as a time interval greater than 60 days from the date of surgery. If chemotherapy is started more than 74 days after surgery, this will be considered as protocol deviation.
5. Gonadotoxicity of chemotherapy will be evaluated AMH level and AFC, and in terms of chemotherapy-induced amenorrhea defined as a time interval from last periods greater than 90 days. Premature ovarian failure and chemotherapy-induced definitive menopause are defined as a time interval from last periods greater than 1 year and 2 years, respectively.
6. All pregnancies will be reported with the type of pregnancy (spontaneous versus assisted pregnancy without or with frozen gametes) and the pregnancy outcome (miscarriage or live birth, single or multiple) over a 10–year period after the end of chemotherapy or until 43 years old
7. Disease-free survival is defined as the time interval from the date of surgery until the date of the first relapse (locoregional or metastasic recurrence) or death from any cause. Data will be censored at last follow-up visit for patients alive free of disease
8. OPTIONAL TRANSLATIONAL RESEARCH (ONLY IN LILLE AND MONTPELLIER) Circulating nucleic acids quantification: - Circulating miRNAs will be extracted from serum samples and then they will be quantified by quantitative real-time RT-PCR. - Quantification of cell-free DNA in serum samples will be performed by quantitative real-time PCR.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Oscar Lambret

Sponsor organisation

Centre Oscar Lambret

Address

3 Rue Frederic Combemale

City

Lille

Postcode

59000

Country

France

Scientific contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Public contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Locations

1 EU/EEA country · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications