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

NCT ID: NCT04616729

Last Updated: 2023-05-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2025-12-31

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.

Detailed Description

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. A recent meta-analysis of individual patient data from the largest randomised clinical trials in women with early breast cancer indicated beneficial effects of GnRHa ovarian suppression in reducing POI risk and increasing post-chemotherapy pregnancy rates with no negative effect on patients' outcomes. However, it should not be considered as an alternative to cryopreservation strategies in fertility preservation.

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. Replacement of the 0,2mg triptorelin trigger by a GnRH agonist depot has potential to provide this dual action. However, the protracted action of the GnRH agonist depot will result in prolonged stimulation of multiple corpora lutea, which will lead to enhanced production of steroids (estradiol and progesterone) and growth factors such as vascular endothelial growth factor. Consequently, GnRH agonist-induced stimulation of multiple corpora lutea is potentially unsafe in a patient with breast cancer because of the impact of estradiol and progesterone on breast tumour cells. In addition, VEGF may increase the risk of OHSS, which will lead to postponement of cancer treatment. Therefore, short-term cotreatment with GnRH antagonists is needed to induce rapid luteolysis.

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.

Patients will be randomized before start of 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.

Conditions

Breast Cancer Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GnRH agonist Depot form

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.

Group Type: EXPERIMENTAL

Triptorelin 3.75 MG Injection

Intervention Type: DRUG

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

Transvaginal oocyte retrieval

Intervention Type: PROCEDURE

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

GnRH agonist Daily form

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.

Group Type: ACTIVE_COMPARATOR

Transvaginal oocyte retrieval

Intervention Type: PROCEDURE

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

Triptorelin Injection

Intervention Type: DRUG

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

Interventions

Triptorelin 3.75 MG Injection

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

Intervention Type: DRUG

Transvaginal oocyte retrieval

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

Intervention Type: PROCEDURE

Triptorelin Injection

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

Intervention Type: DRUG

Other Intervention Names

Gonapeptyl; Decapeptyl; Gonapeptyl; Decapeptyl

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: collaborator

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michel De Vos, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuis Brussel

Locations

Universitair Ziekenhuis Brussel

Boortmeerbeek, Brussels Capital, Belgium

Site Status: RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, Belgium

Site Status: NOT_YET_RECRUITING

Countries

Belgium

Central Contacts

Michel De Vos, MD PhD

Role: CONTACT

mdv@uzbrussel.be

024776660 ext. 0032

Elsie Nulens

Role: CONTACT

Elsie.Nulens@uzbrussel.be

024776648 ext. 0032

Facility Contacts

Michel De Vos, MD

Role: primary

mdv@uzbrussel.be

024776660 ext. 0032

Michel De Vos

Role: backup

mdv@uzbrussel.be

024776660

Sharon Lie Fong, MD PhD

Role: primary

016343650 ext. 0032

References

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.

Reference Type: BACKGROUND

PMID: 27940355 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29718793 (View on PubMed)

Other Identifiers

2019DEPO-TRIGGER001

Identifier Type: -

Identifier Source: org_study_id