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Evaluation of Individual Sensitivity to the Gonadotoxicity of Chemotherapy in Young Patients With Breast Cancer (ESIGON)

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ClinicalTrials.gov Identifier: NCT03731845
Recruitment Status : Recruiting
First Posted : November 6, 2018
Last Update Posted : October 2, 2019
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Over the past decade, advances in diagnosis and treatments have dramatically increased the rates of cure for young patients with cancer. As a consequence, a new population of cancer survivors has emerged whose fertility is compromised after cancer therapy. Indeed, gonadotoxicity is a well-known long-term side effect of cancer treatment in young patients having survived malignant diseases. More than 80% of women of childbearing age, treated for breast cancer with standard protocol of neoadjuvant (4 cycles of 5-fluorouracile - epirubicin- cyclophosphamide (FEC) and 4 cycles of docetaxel) or adjuvant chemotherapy (3 FEC and 3 docetaxel), show an alteration of their ovarian reserve 2 years after completion of the treatment, as a result of chemotherapy-related follicular loss. Therefore, according to the extent of the follicular damages, the gonadal function may vary from moderate to severe diminished ovarian reserve (DOR) and possibly to the ultimate stage of premature ovarian insufficiency (POI).

Investigators propose a multicentric and prospective study of a cohort of young women with breast cancer to evaluate whether genetic polymorphisms, previously identified as being correlated with age at menopause in the healthy population, are associated with the intensity of the follicular decline following chemotherapy in young breast cancer survivors.


Condition or disease Intervention/treatment Phase
Breast Cancer Genetic: Blood sample for genetic test Biological: Blood sample for hormonal measurement Other: Ovarian ultrasound scan Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Evaluation of Individual Sensitivity to the Gonadotoxicity of Chemotherapy in Young Patients With Breast Cancer
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : October 2026
Estimated Study Completion Date : January 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: patient Genetic: Blood sample for genetic test
Patients will be genotyped for single nucleotide polymorphism previously found to be associated with age at natural menopause

Biological: Blood sample for hormonal measurement
at each visit : 2x7ml. At the end of the study hormonal measurements (AMH, P4, LH, FSH, E25)

Other: Ovarian ultrasound scan
Ovarian ultrasound scan at follow up visits (Y1,Y1.5, Y2.5 Y3.5 Y4.5 Y5.5)




Primary Outcome Measures :
  1. Assessment of ovarian reserve [ Time Frame: 5 years after completion of chemotherapy ]

    is an aggregated measure of FSH, AMH serum level, Antral Follicle Count and menstrual profile :

    • Normal ovarian reserve: persistence of menstrual cycle, FSH<40 IU/L and AMH>1.1 ng/mL or AFC>7 follicles
    • Moderate diminished ovarian reserve : persistence of menstrual cycle, FSH<40 IU/L and 0.5≤AMH≤1.1 ng/mL or 5≤AFC≤7 follicles
    • Severe diminished ovarian reserve : persistence of menstrual cycle and AMH<0.5 ng/mL or AFC<5 follicles
    • Premature ovarian insufficiency is defined by amenorrhea above four months and FSH level ≥40 IU/L in women before 40 years.

    AMH serum levels and ultrasonographic evaluation of AFC will be evaluated FIVEyears after the end of chemotherapy.



Secondary Outcome Measures :
  1. Menstrual profile: amenorrhea, spaniomenorrhea, normal cycle length (28-35 days) [ Time Frame: 5 years ]
    To evaluate the association between genetic polymorphisms and other parameters related to female fertility after chemotherapy such as the menstrual cycle profile. These data will be obtained from clinical interrogatory performed by medical doctors.

  2. Pregnancy rates [ Time Frame: 5 years ]
    These data will be obtained from clinical interrogatory performed by medical doctors.

  3. AMH level [ Time Frame: 6, 12, 24, 36, 48, 60 months following the end of chemotherapy. ]
    To assess the evolution of ovarian reserve tests at the end of chemotherapy AMH level will be performed before the initiation of chemotherapy and 6, 12, 24, 36, 48, 60 months following the end of chemotherapy.

  4. Antral Follicle Count (Ultrasound evaluation) [ Time Frame: 6, 12, 24, 36, 48, 60 months following the end of chemotherapy. ]
    To assess the evolution of ovarian reserve tests at the end of chemotherapy Measurements of ultrasonographic AFC will be performed before the initiation of chemotherapy and 6, 12, 24, 36, 48, 60 months following the end of chemotherapy.

  5. Follicular decline (definition below) [ Time Frame: 2 years after the completion of chemotherapy ]
    A follicular decline will be defined as a moderate/severe DOR or a POI



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Ages Eligible for Study:   18 Years to 36 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: 18 - 36 years
  • Diagnosis of breast cancer
  • BMI≤30 Kg/m2
  • Baseline antral Follicular count (before initiation of chemotherapy): 10-40 follicles measuring 2 - 9 mm in diameter
  • Regular and ovulatory menstrual cycles
  • Indication of neoadjuvant (4 FEC and 4 docetaxel) or adjuvant (3 FEC and 3 docetaxel) chemotherapy
  • Free informed and written consent, dated and signed by the patient and the investigator
  • Patient affiliated to the French National Social Security System

Non inclusion criteria

  • Previous history of chemotherapy
  • History of ovarian surgery or endometrioma
  • Ovarian Polycystic Syndrome
  • DOR or POI before chemotherapy
  • Virgin patients

Exclusion Criteria:

- Intensification of chemotherapy


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03731845


Contacts
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Contact: Charlotte SONIGO, MD 01 45 37 40 53 charlotte.sonigo@aphp.fr
Contact: Marie GODARD 00 33 1 58 41 34 78 marie.godard@aphp.fr

Locations
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France
Antoine Béclère Hospital Recruiting
Clamart, France, 92140
Contact: Charlotte SONIGO, MD       charlotte.sonigo@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
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Principal Investigator: Charlotte SONIGO, MD Assistance Publique - Hôpitaux de Paris
Study Chair: Michael Grynberg, MD, PhD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03731845     History of Changes
Other Study ID Numbers: K160913J
2017-A02111-52 ( Other Identifier: ID-RCB )
First Posted: November 6, 2018    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Breast Cancer
ovarian reserve
primary ovarian insufficiency
chemotherapy
single nucleotide polymorphism
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases