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

Breast Cancer Female Clinical Trial

— Depo-Trigger  

Official title:

DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation in Breast Cancer Patients Undergoing Fertility Preservation: a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04616729
• Other study ID #: 2019DEPO-TRIGGER001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2023
• Source: Universitair Ziekenhuis Brussel
• Contact: Michel De Vos, MD PhD
• Phone: 024776660
• Email: mdv[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms

Intervention

Drug:
• Triptorelin 3.75 MG Injection
Depot Group (Group A) will receive Triptorelin 3.75mg Depot form for final oocyte maturation.

Procedure:
• Transvaginal oocyte retrieval
Patients in both groups will undergo a transvaginal oocyte retrieval after ovarian stimulation.

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

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Boortmeerbeek	Brussels
Belgium	Universitaire Ziekenhuizen Leuven	Leuven	Vlaams-Brabant

Sponsors (2)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel	Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

References & 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Number of cumulus-oocyte complexes	Evaluation of the number of cumulus-oocyte complexes between the Depot Group and Daily Group	During the procedure of the transvaginal oocyte retrieval
Secondary	Number of Metaphase II oocytes	Evaluation of the number of Metaphase II oocytes between the Depot group and Daily group	Immediately after the procedure of the transvaginal oocyte retrieval
Secondary	Evaluation of climacteric symptoms	Assessment of MENQOL (The Menopause-Specific Quality of Life) Questionnaire	One week after the transvaginal oocyte retrieval (on day 7)