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Triptorelin Pamoate

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Ganirelix

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Contraceptive Agents, Female

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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.

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.

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

Triptorelin 3.75 MG Injection

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

Transvaginal oocyte retrieval

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

Triptorelin Injection

Michel De Vos, MD PhD

Elsie Nulens

Michel De Vos, MD

Michel De Vos

Sharon Lie Fong, MD PhD

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.

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.

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.

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

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

As this is a multicenter study, we plan to share IPD between the study sites. An electronically 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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Evaluation of the number of cumulus-oocyte complexes between the Depot Group and Daily Group

Evaluation of the number of Metaphase II oocytes between the Depot group and Daily group

Assessment of MENQOL (The Menopause-Specific Quality of Life) Questionnaire

Universitaire Ziekenhuizen KU Leuven

Universitair Ziekenhuis Brussel

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Androgens

Hormone Antagonists

Stereotactic body radiotherapy to 27 Gy in 3 fractions to uninvolved regions of the prostate glad and up to 39 Gy in 3 fractions to mpMRI-defined intraprostatic lesions, with concurrent/adjuvant androgen deprivation therapy (6 months for intermediate risk, 24 months for high risk)

Prostate stereotactic body radiotherapy delivered to 27 Gy in 3 fractions on alternating days to uninvolved regions with up to 39 Gy in 3 fractions delivered to mpMRI-defined intraprostatic lesions

Prostate SBRT with Focal Boost

Six months of androgen deprivation therapy for intermediate-risk localized prostate cancer and 24 months for high-risk localized prostate cancer

Scott Grimes

Scott C Morgan, MD, MSc

External beam radiotherapy combined with androgen deprivation therapy is a standard treatment option for localized prostate cancer. The current standard involves delivering radiotherapy uniformly throughout the prostate gland in daily fractions, five days per week, for approximately four weeks. In this study, radiotherapy will be delivered using an ultra-hypofractionated approach in three larger fractions on alternating days over one week Multiparametric magnetic resonance imaging will be used to guide focal dose escalation to parts of the gland harboring tumor, which could potentially reduce the risk of cancer recurrence compared to standard dose of radiotherapy. The aim of this study is to confirm that this approach can be delivered safely, that is, with rates of urinary and bowel side effects at 1 year of follow-up that are not significantly greater than the current standard.

External beam radiotherapy (RT) in combination with androgen deprivation therapy (ADT) is a standard definitive treatment for localized prostate cancer. It confers long-term oncologic outcomes equivalent to those of radical prostatectomy. The current standard approach for prostate RT consists of uniform irradiation of the entire gland. This technique employs computed tomography (CT) images for planning, in which disease is not readily apparent. Multiparametric magnetic resonance imaging (mpMRI) of the prostate allows for accurate visualization of clinically significant tumour foci within the prostate gland. It thereby permits selective escalation of dose to tumours within the gland - a so-called focal boost or "microboost" - with the aim of improving treatment efficacy.

The current standard approach to prostate RT involves delivery of treatment in daily fractions, five days per week, over four weeks. Prostate cancer appears to exhibit an uncommon fractionation sensitivity among solid tumours. A consequence of this is that hypofractionation - that is, delivery of RT with larger fraction sizes - may further improve the therapeutic ratio. A number of large-scale studies have shown promise for an ultra-hypofractionated approach (that is, larger than 5-Gy fractions) in the treatment of localized prostate cancer.

There is an unmet need for innovations in radiotherapy that further reduce the risk of relapse without increasing toxicity or compromising health-related quality of life and that reduce the treatment burden. Both focal intraprostatic boosts - informed by mpMRI findings - and ultra-hypofractionation represent promising approaches to achieve this objective. To date, the optimal regimen that combines these two innovations remains to be explored. In this trial, we will investigate in a single-arm prospective cohort the safety of an mpMRI-defined focal boost technique with a convenient and radiobiologically compelling ultra-hypofractionated radiotherapy regimen (consisting of three fractionas delivered over one week) for localized unfavourable intermediate and high-risk localized prostate cancer.

This is a single-arm prospective trial conducted in patients with unfavourable intermediate-risk or high-risk localized prostate cancer. Treatment consists of ultra-hypofractionated intensity-modulated, image-guided prostate radiotherapy delivered to 27 Gy in 3 fractions (1 fraction per day every other day, over a 5 day period) to uninvolved regions, with up to 39 Gy in 3 fractions delivered to mpMRI-defined intraprostatic lesions, assuming normal tissue dosimetric criteria can be safely met. Radiotherapy will be combined with concurrent/adjuvant androgen deprivation therapy (6 months duration in patients with intermediate-risk disease and 24 months for patients with high-risk disease). There will be follow-up assessments for toxicity, quality of life, and biochemical control. The primary endpoint will be prevalence of grade ≥ 2 genitourinary or gastrointestinal toxicity at 12 months.

Primary Objective The primary objective is to determine whether, in a population of men with unfavourable intermediate-risk or high-risk localized prostate cancer receiving a combination of three-fraction ultra-hypofractionated RT and adjuvant androgen deprivation therapy, an mpMRI-defined focal boost can be delivered with acceptable GU and GI toxicity at 1 year of follow-up.

Secondary Objectives

The secondary objectives are to evaluate, in a population of men with unfavourable intermediate-risk or high-risk localized prostate cancer, the effects of an mpMRI-defined focal boost on:

* Health-related quality of life
* Biochemical disease-free survival

Prostate radiotherapy of 27 Gy in 3 fractions to uninvolved regions, up to 39 Gy in 3 fractions to mpMRI-defined intraprostatic lesions, with concurrent/adjuvant androgen deprivation therapy (6 months intermediate risk, 24 months for high risk)

Dose Escalation For INtraprostatic LEsions

A Phase II Study of the Use of MRI-defined Focal Boosts With Stereotactic Body Radiotherapy for Localized Prostate Cancer

Number of patients with grade 2 or greater genitourinary or gastrointestinal toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE ) version 5.0 and Radiation Therapy Oncology Group radiation toxicity scale

Measured by Expanded Prostate Cancer Index Composite (EPIC)-26 bowel and urinary domains

Number of patients free of biochemical recurrence (defined according to the Phoenix definition as an increase in serum PSA that is ≥ 2 ng/mL above the nadir value observed following radiotherapy) or death from any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation	NCT04616729	Breast Cancer F...	Triptorelin 3.7... Transvaginal oo... Triptorelin Inj...	18 Years - 35 Years	Universitair Ziekenhuis Brussel
DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation	NCT04616729	Breast Cancer F...	Triptorelin 3.7... Transvaginal oo... Triptorelin Inj...	18 Years - 35 Years	Universitair Ziekenhuis Brussel
DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation	NCT04616729	Breast Cancer F...	Triptorelin 3.7... Transvaginal oo... Triptorelin Inj...	18 Years - 35 Years	Universitair Ziekenhuis Brussel
Dose Escalation For INtraprostatic LEsions	NCT05851547	Prostatic Neopl...	Prostate SBRT w... Triptorelin Inj...	18 Years -	Ottawa Hospital Research Institute

Spots Global Cancer Trial Database for triptorelin injection