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Combining Interventions of Fertility Preservation to Mitigate Fertility Loss After Breast Cancer (Coimbra)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04586686
Recruitment Status : Not yet recruiting
First Posted : October 14, 2020
Last Update Posted : October 14, 2020
Sponsor:
Collaborator:
Hopital Antoine Beclere
Information provided by (Responsible Party):
Universitair Ziekenhuis Brussel

Brief Summary:
This clinical prospective randomised controlled trial will evaluate the impact of an ovarian biopsy on the oocyte yield after controlled ovarian stimulation before chemotherapy in view of breast cancer. The purpose of this trial is to learn about the possibility to combine these two fertility preservation procedures without decreasing the number of oocytes collected after an ovarian stimulation.

Condition or disease Intervention/treatment Phase
Breast Cancer Female Procedure: Ovarian biopsy via laparoscopy Procedure: Transvaginal oocyte retrieval Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: All patients will undergo a laparoscopy for an ovarian biopsy (about 20% of the ovarian volume). The side of the ovarian biopsy will be randomized on the day of the laparoscopy either from the right side (group 1) or from the left side (group 2). All patients will then continue with a controlled ovarian stimulation, using corifollitropin alpha and follitropin beta in a GnRH antagonist protocol using ganirelix. The metaphase II oocyte yield will be evaluated between the biopsied versus non-biopsied ovary to proof a non-inferiority (assuming that a difference of 1 metaphase II oocyte yielded from the biopsied ovary compared to the non-biopsied ovary is not clinically relevant).
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Combining Interventions of Fertility Preservation to Mitigate Fertility Loss After
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : November 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Group 1: right ovarian biopsy
Patients in group 1 will undergo a laparoscopy for an ovarian biopsy from the right ovary. They will then continue with a controlled ovarian stimulation, using a GnRH antagonist protocol. This will be started with Corifollitropin alfa 0.15 mg in the evening. On day six the antagonist, Ganirelix, will be added in the morning. If needed stimulation can be continued after seven days using follitropin beta daily in the evening (dosage ranging from 200-300 IE depending on AMH levels). Agonist trigger Triptorelin 0.2 mg will be administered for ovulation induction. In case of LH levels <2 IU/L at the start of ovarian stimulation, a dual ovulation strategy will be adapted: Triptorelin 0.2mg and choriongonadotropin 2500 IU (or choriongonadotropin alfa 250 µg) will be given. A transvaginal oocyte retrieval will be planned 36 hours after triggering.
Procedure: Ovarian biopsy via laparoscopy
A laparoscopy will be performed to achieve an ovarian cortical biopsy of one of both ovaries. Approximately twenty % of the ovarian volume as initially measured on the baseline ultrasound at the first visit will be removed to be processed in the lab for cortex freezing. The laparoscopic procedure in order to take the ovarian cortex biopsy will be standardised as much as possible. The technique developed by ProFam will be followed and adapted if needed by the surgeon's discretion. A three to four port laparoscopy will be used. The ovarian cortex biopsy will be taken using a curved scissor. Bipolar or unipolar cauterisation will be avoided as much as possible. If necessary for approximation or for hemostatic reasons, the ovarian edges can be stitched or Surgicel ® Absorbable Hemostat can be used.

Procedure: Transvaginal oocyte retrieval
After ovarian stimulation, a transvaginal oocyte retrieval will be performed either under local or general anaesthetics (patient's choice). The oocyte yield between the biopsied and non-biopsied ovary will be evaluated.

Group 2: left ovarian biopsy
Patients in group 2 will undergo a laparoscopy for an ovarian biopsy from the left ovary. They will then continue with a controlled ovarian stimulation, using a GnRH antagonist protocol. This will be started with Corifollitropin alfa 0.15 mg in the evening. On day six the antagonist, Ganirelix, will be added in the morning. If needed stimulation can be continued after seven days using follitropin beta daily in the evening (dosage ranging from 200-300 IE depending on AMH levels). Agonist trigger Triptorelin 0.2 mg will be administered for ovulation induction. In case of LH levels <2 IU/L at the start of ovarian stimulation, a dual ovulation strategy will be adapted: Triptorelin 0.2mg and choriongonadotropin 2500 IU (or choriongonadotropin alfa 250 µg) will be given. A transvaginal oocyte retrieval will be planned 36 hours after triggering.
Procedure: Ovarian biopsy via laparoscopy
A laparoscopy will be performed to achieve an ovarian cortical biopsy of one of both ovaries. Approximately twenty % of the ovarian volume as initially measured on the baseline ultrasound at the first visit will be removed to be processed in the lab for cortex freezing. The laparoscopic procedure in order to take the ovarian cortex biopsy will be standardised as much as possible. The technique developed by ProFam will be followed and adapted if needed by the surgeon's discretion. A three to four port laparoscopy will be used. The ovarian cortex biopsy will be taken using a curved scissor. Bipolar or unipolar cauterisation will be avoided as much as possible. If necessary for approximation or for hemostatic reasons, the ovarian edges can be stitched or Surgicel ® Absorbable Hemostat can be used.

Procedure: Transvaginal oocyte retrieval
After ovarian stimulation, a transvaginal oocyte retrieval will be performed either under local or general anaesthetics (patient's choice). The oocyte yield between the biopsied and non-biopsied ovary will be evaluated.




Primary Outcome Measures :
  1. Mature oocyte yield from biopsied versus non-biopsied ovary [ Time Frame: Immediately after the procedure of the transvaginal oocyte retrieval ]
    Evaluation of metaphase II oocyte yield between biopsied and non-biopsied ovary


Secondary Outcome Measures :
  1. Follicle Output Rate (FORT) [ Time Frame: From ovarian stimulation until the day of oocyte retrieval (2-3 weeks, depending on patient's response) ]
    Evaluation of the proportion of follicles that were responsive to FSH and is calculated by dividing the number of preovulatory follicles (16-20 mm) × 100 by the antral follicle count (3-8 mm)

  2. COC yield [ Time Frame: During the procedure of the transvaginal oocyte retrieval ]
    Evaluation of cumulus oophorus complex yield between biopsied and non-biopsied ovary

  3. Maturation Rate [ Time Frame: Immediately after the procedure of the transvaginal oocyte retrieval ]
    Evaluation of proportion of metaphase II oocytes within the COC yield between biopsies and non-biopsied ovary



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 and ≤ 35 years
  • BMI ≥ 18 and ≤ 35 kg/m²
  • Diagnosis of breast cancer
  • Presence of 2 ovaries
  • Signed informed consent form
  • Medically fit for general anesthesia (ASA score 1-3)
  • Permission of oncology team (with agreement to postpone chemo/radiotherapy for at least 2 weeks)
  • Random start controlled ovarian stimulation
  • AFC minimum (ie antral follicles measuring between 2-9 mm): 8 antral follicles

Exclusion Criteria:

  • Age <18 or >35 years
  • BMI <18 or >35 kg/m²
  • Difference in AFC between the ovaries of more than 7 antral follicles
  • Diagnosis of PCOS
  • Previous radiotherapy and/or chemotherapy (neo-adjuvant chemotherapy included)
  • Endometriose rAFS 3-4
  • Allergy or reaction to the use of Elonva®, Puregon®, Orgalutran®, Pregnyl® Gonapeptyl®, Decapeptyl® or letrozole in the past

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): NCT04586686


Contacts
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Contact: Sien Delattre, MD (0)473272422 ext 0032 sien.delattre@uzbrussel.be
Contact: Elsie Nulens (0)24776648 ext 0032 Elsie.Nulens@uzbrussel.be

Locations
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Belgium
Universitair Ziekenhuis Brussel
Brussels, Belgium, 1090
Contact: Sien Delattre, MD    (0)473272422 ext 0032    sien.delattre@uzbrussel.be   
Principal Investigator: Michel De Vos, MD PhD         
France
Service de Médecine de la Reproduction et Préservation de la Fertilité, Hôpital Antoine Béclère
Paris, France, 92140
Contact: Michaël Grynberg, MD PhD    (0)145374053 ext 0033    michael.grynberg@aphp.fr   
Principal Investigator: Michaël Grynberg, MD PhD         
Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Hopital Antoine Beclere
Investigators
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Principal Investigator: Michel De Vos, MD PhD Universitair Ziekenhuis Brussel
Publications of Results:
Other Publications:

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Responsible Party: Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT04586686    
Other Study ID Numbers: 2019COIMBRA001
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: As this is a multicenter study, we plan to share IPD between the study sites. An electronical case report form (eCRF) will be set up and completed in all sites. Data will be handled in accordance with the general data protection regulation (GDPR).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: The data will become available over the course of the study until 6 months after ending this study. This will give us the time to analyse the data of the different sites.
Access Criteria: eCRF

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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 Universitair Ziekenhuis Brussel:
Fertility Preservation
Reproductive Techniques, assisted
Ovulation Induction
Oocyte Retrieval
Cryopreservation
Ovary
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases