DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation

NCT04616729 | Unknown Phase 1

• 1 other identifier: 2019DEPO-TRIGGER001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

For breast cancer patients who are candidates to receive chemotherapy, concurrent use of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) can be offered as ovarian protection. Because ovarian stimulation for oocyte cryopreservation is usually performed using a GnRH antagonist protocol and typically involves final oocyte maturation triggering with a GnRH agonist, the investigators designed this study to explore the feasibility of combining the final oocyte maturation trigger and the start of ovarian suppression. Short-term cotreatment with GnRH antagonists is needed to induce rapid luteolysis (in view of prevention of ovarian hyperstimulation). To demonstrate the safety of GnRH agonist depot triggering followed by daily GnRH antagonist luteolysis, this pilot study is set out to analyse the endocrine profile and ovarian morphology of this novel protocol.

Conditions

Breast Cancer Female

Keywords

Fertility preservation; Reproductive Techniques, assisted; Ovulation Induction; Oocyte Retrieval; Cryopreservation

Outcome Measures

Primary Outcomes (13)

• Safety profile with regard to the risk of OHSS: assessment of change in ovarian volume

  A transvaginal ultrasound will be performed to measure the ovarian volume according to the formula 'length x width x height x 0.523' mm³. In the assumption of safety ovarian volume should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in hematocrit

  A blood sample will be taken to evaluate hematocrit (%). In the assumption of safety hematocrit levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in hemoglobine

  A blood sample will be taken to evaluate hemoglobine (g/dL). In the assumption of safety hemoglobine levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in White Blood cell Count

  A blood sample will be taken to evaluate White Blood cell Count (X10³/mm³). In the assumption of safety White Blood cell Count should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in Platelet Count

  A blood sample will be taken to evaluate Platelet Count (X10³/mm³). In the assumption of safety Platelet Count should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in estimated glomerular filtration rate (eGFR)

  A blood sample will be taken to evaluate eGFR (mL/min/1.73m²). In the assumption of safety eGFR levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in Creatinine

  A blood sample will be taken to evaluate Creatinine (mg/dL). In the assumption of safety creatinine levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in Albumin

  A blood sample will be taken to evaluate Albumin (g/L). In the assumption of safety Albumin levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in liver function (AST, ALT, Gamma-GT, bilirubine, LDH)

  A blood sample will be taken to evaluate liver function (AST U/L, ALT U/L, Gamma-GT U/L, bilirubine mg/dL, LDH U/L). In the assumption of safety liver function levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in Oestradiol (E2)

  A blood sample will be taken to evaluate Oestradiol (ng/L). In the assumption of safety Oestradiol levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in Progesteron

  A blood sample will be taken to evaluate Progesteron (mcg/L). In the assumption of safety Progesteron levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in Follicle Stimulating Hormone (FSH)

  A blood sample will be taken to evaluate FSH (IU/L). In the assumption of safety FSH levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

• Safety profile with regard to the risk of OHSS: assessment of change in Luteinizing Hormone (LH)

  A blood sample will be taken to evaluate LH (IU/L). In the assumption of safety LH levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome.

  During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)

Secondary Outcomes (3)

• Number of cumulus-oocyte complexes

  During the procedure of the transvaginal oocyte retrieval

• Number of Metaphase II oocytes

  Immediately after the procedure of the transvaginal oocyte retrieval

• Evaluation of climacteric symptoms

  One week after the transvaginal oocyte retrieval (on day 7)

Study Arms (2)

GnRH agonist Depot form

EXPERIMENTAL

Ovarian stimulation will be performed using a fixed antagonist protocol with Follitropin Alfa (daily in the evening) and Ganirelix or Cetrorelix (daily in the morning). Selection of the daily gonadotropin dose will be based on ovarian reserve parameters (AMH and AFC) and BMI. Co-administration of 5 mg of letrozole daily (in the morning) commencing on the first day of gonadotropin administration and continuing throughout the ovarian stimulation will be performed as this reduces oestradiol concentrations. GnRH agonist Triptorelin 3.75 mg Depot form will be used for final oocyte maturation. Ganirelix/Cetrorelix 0.25mg daily (in the morning) will resume for 7 days from the evening of the day of oocyte retrieval onwards. Hormone analysis, analysis of haematology and biochemistry and a pelvic ultrasound scan will be done on days 3, 5 and 7 after oocyte retrieval.

Drug: Triptorelin 3.75 MG Injection; Procedure: Transvaginal oocyte retrieval

GnRH agonist Daily form

ACTIVE COMPARATOR

Ovarian stimulation will be performed using a fixed antagonist protocol with Follitropin Alfa (daily in the evening) and Ganirelix/Cetrorelix (daily in the morning). Selection of the daily gonadotropin dose will be based on ovarian reserve parameters (AMH and AFC) and BMI. Co-administration of 5 mg of letrozole daily (in the morning) commencing on the first day of gonadotropin administration and continuing throughout the ovarian stimulation will be performed as this reduces oestradiol concentrations. GnRH agonist Triptorelin 0.2 mg Daily form will be used for final oocyte maturation. Hormone analysis, analysis of haematology and biochemistry and a pelvic ultrasound scan will be done on days 3, 5 and 7 after oocyte retrieval. The first administration of Triptorelin 3.75mg depot will be scheduled on the first day of the menstrual cycle after oocyte retrieval. To prevent the flare-up produced by the GnRH agonist, daily doses of 0.25mg of Ganirelix/Cetrorelix will be given for seven days.

Procedure: Transvaginal oocyte retrieval; Drug: Triptorelin Injection

Interventions

Triptorelin 3.75 MG Injection DRUG

Depot Group (Group A) will receive Triptorelin 3.75mg Depot form for final oocyte maturation.

Also known as: Gonapeptyl, Decapeptyl

GnRH agonist Depot form

Transvaginal oocyte retrieval PROCEDURE

Patients in both groups will undergo a transvaginal oocyte retrieval after ovarian stimulation.

GnRH agonist Daily form; GnRH agonist Depot form

Triptorelin Injection DRUG

Daily Group (Group B) will receive Triptorelin 0.2mg Daily form for final oocyte maturation.

Also known as: Gonapeptyl, Decapeptyl

GnRH agonist Daily form

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age \<36y
• BMI ≥ 18 and ≤ 35 kg/m²
• Early stage breast cancer
• Any hormone receptor status
• Any HER status
• Cryopreservation of oocytes and/or embryos
• Oncologist's approval to participate to the DEPO-trigger trial
• Signed informed consent form

You may not qualify if:

• Contra-indications for controlled ovarian stimulation or oocyte retrieval
• Necessity of neo-adjuvant chemotherapy

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (2)

Universitair Ziekenhuis Brussel

Boortmeerbeek, Brussels Capital, 3190, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

NOT YET RECRUITING

Related Publications (2)

• Lambertini M, Cinquini M, Moschetti I, Peccatori FA, Anserini P, Valenzano Menada M, Tomirotti M, Del Mastro L. Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology. Eur J Cancer. 2017 Jan;71:25-33. doi: 10.1016/j.ejca.2016.10.034. Epub 2016 Dec 9.

  PMID: 27940355 BACKGROUND

• Lambertini M, Moore HCF, Leonard RCF, Loibl S, Munster P, Bruzzone M, Boni L, Unger JM, Anderson RA, Mehta K, Minton S, Poggio F, Albain KS, Adamson DJA, Gerber B, Cripps A, Bertelli G, Seiler S, Ceppi M, Partridge AH, Del Mastro L. Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data. J Clin Oncol. 2018 Jul 1;36(19):1981-1990. doi: 10.1200/JCO.2018.78.0858. Epub 2018 May 2.

  PMID: 29718793 BACKGROUND

MeSH Terms

Conditions

Helping Behavior

Interventions

Triptorelin Pamoate; Injections

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Michel De Vos, MD PhD

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michel De Vos, MD PhD

CONTACT

024776660; mdv@uzbrussel.be

Elsie Nulens

CONTACT

024776648; Elsie.Nulens@uzbrussel.be

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized before start of ovarian stimulation to either DEPOT group (group A) or control group (group B), only after patient eligibility has been established and patient consent has been obtained. Group A will receive the GnRH agonist Depot form for final oocyte maturation followed by daily GnRH antagonist injections for 1 week. Group B will receive the GnRH agonist daily form for final oocyte maturation. After one week the Depot form combined with daily GnRH antagonist injections for 7 days, will be administered in view of ovarian protection during chemotherapy. Blood analysis and ultrasounds will be organised on day 3, 5 and 7 after oocyte pick-up in both groups.

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: November 5, 2020
• Study Start: November 1, 2022
• Primary Completion: November 30, 2025
• Study Completion: December 31, 2025
• Last Updated: May 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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

Locations

BE (2)