- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04616729
DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation (Depo-Trigger)
DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation in Breast Cancer Patients Undergoing Fertility Preservation: a Pilot Study
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Elsie Nulens
- Phone Number: 0032 024776648
- Email: Elsie.Nulens@uzbrussel.be
Study Contact Backup
- Name: Michel De Vos, MD PhD
- Phone Number: 0032 024776660
- Email: mdv@uzbrussel.be
Study Locations
-
-
Brussels
-
Boortmeerbeek, Brussels, Belgium, 3190
- Recruiting
- Universitair Ziekenhuis Brussel
-
Principal Investigator:
- Michel De Vos, MD PhD
-
Contact:
- Michel De Vos, MD
- Phone Number: 0032 024776660
- Email: mdv@uzbrussel.be
-
Contact:
- Michel De Vos
- Phone Number: 024776660
- Email: mdv@uzbrussel.be
-
-
Vlaams-Brabant
-
Leuven, Vlaams-Brabant, Belgium, 3000
- Not yet recruiting
- Universitaire Ziekenhuizen Leuven
-
Contact:
- Sharon Lie Fong, MD PhD
- Phone Number: 0032 016343650
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Depot Group (Group A) will receive Triptorelin 3.75mg Depot form for final oocyte maturation.
Other Names:
Patients in both groups will undergo a transvaginal oocyte retrieval after ovarian stimulation.
|
Active Comparator: 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.
|
Patients in both groups will undergo a transvaginal oocyte retrieval after ovarian stimulation.
Daily Group (Group B) will receive Triptorelin 0.2mg Daily form for final oocyte maturation.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety profile with regard to the risk of OHSS: assessment of change in ovarian volume
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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)
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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)
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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)
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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)
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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)
Time Frame: During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of cumulus-oocyte complexes
Time Frame: During the procedure of the transvaginal oocyte retrieval
|
Evaluation of the number of cumulus-oocyte complexes between the Depot Group and Daily Group
|
During the procedure of the transvaginal oocyte retrieval
|
Number of Metaphase II oocytes
Time Frame: Immediately after the procedure of the transvaginal oocyte retrieval
|
Evaluation of the number of Metaphase II oocytes between the Depot group and Daily group
|
Immediately after the procedure of the transvaginal oocyte retrieval
|
Evaluation of climacteric symptoms
Time Frame: One week after the transvaginal oocyte retrieval (on day 7)
|
Assessment of MENQOL (The Menopause-Specific Quality of Life) Questionnaire
|
One week after the transvaginal oocyte retrieval (on day 7)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michel De Vos, MD PhD, Universitair Ziekenhuis Brussel
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Contraceptive Agents, Hormonal
- Contraceptive Agents
- Reproductive Control Agents
- Contraceptive Agents, Female
- Luteolytic Agents
- Triptorelin Pamoate
Other Study ID Numbers
- 2019DEPO-TRIGGER001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer Female
-
Institut fuer FrauengesundheitNovartis Pharmaceuticals; AGO Breast Study Group e.V.RecruitingBreast Cancer | Breast Neoplasms | Advanced Breast Cancer | Breast Neoplasm Female | Breast Cancer Female | HER2-negative Breast Cancer | Hormone Receptor-positive Breast CancerGermany
-
H. Lee Moffitt Cancer Center and Research InstituteNovartisCompletedBreast Cancer | Breast Cancer - Female | Breast Cancer - MaleUnited States
-
Quanta MedicalLattice MedicalRecruitingBreast Reconstruction | Breast Cancer Female | Breast Cancer PreventGeorgia, France
-
Masaryk UniversityMasaryk Memorial Cancer InstituteRecruitingBreast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Female | Breast Cancer Stage IIICzechia
-
University of ChicagoRecruitingBreast Cancer | HER2-positive Breast Cancer | Breast Cancer Stage II | Breast Cancer Female | Breast Cancer Stage IIINigeria
-
University of Illinois at ChicagoRecruitingBreast Cancer Female | Breast Cancer InvasiveUnited States
-
Ahon Pharmaceutical Co., Ltd.RecruitingAdvanced Breast Cancer | Female Breast CancerChina
-
Ahon Pharmaceutical Co., Ltd.RecruitingAdvanced Breast Cancer | Female Breast CancerChina
-
Institut fuer FrauengesundheitSamsung Bioepis Co., Ltd.RecruitingBreast Cancer | Breast Neoplasms | HER2-positive Breast Cancer | Breast Cancer FemaleGermany
-
Wake Forest University Health SciencesAtrium Health NavicentActive, not recruitingBreast Cancer Female | Early-stage Breast CancerUnited States
Clinical Trials on Triptorelin 3.75 MG Injection
-
Azienda Ospedaliera S. Maria della MisericordiaCompleted
-
AbbottFraktal.com.pl; Med-net.plCompletedLower Urinary Tract Symptoms | Advanced Prostate CancerPoland, Ukraine
-
Aristotle University Of ThessalonikiEugonia IVF Unit, Athens, GreeceUnknown
-
Joseph MccuneEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsTerminatedLupus Erythematosus, Systemic | Systemic Vasculitis | Lung Disease With Systemic Sclerosis | Isolated Angiitis of Central Nervous System | Lung Disease Interstitial DiffuseUnited States
-
Elisha HospitalMerck Sharp & Dohme LLCTerminatedOvarian Hyperstimulation SyndromeIsrael
-
IpsenCompletedDeep Infiltrating Endometriosis (DIE)China
-
Masaryk UniversityMinistry of Health, Czech RepublicCompletedHodgkin Disease | Hodgkin LymphomaCzech Republic
-
Debiopharm International SAQuintiles, Inc.Completed
-
Centre Hospitalier Universitaire Ibn RochdCompleted