Co-treatment With GnRH Analogs on the Ovarian Reserve in Young Women Treated With Alkylating Agents for Cancer (PRESOV)

Assessment of the Effect of a Co-treatment With GnRH Analogs on the Ovarian Reserve in Adolescents and Young Women Treated With Alkylating Agents for Cancer

The purpose of this study is to determine the efficacy of a temporary ovarian suppression obtained by administration of a gonadotropin releasing hormone agonist during alkylating agents containing chemotherapy on ovarian reserve assessed by Anti-Müllerian hormone (AMH) serum levels in adolescents and young women with cancer.

Study Overview

• Status: Unknown
• Conditions: Sarcoma; Lymphoma; Cancer; Osteosarcoma; Ewing Sarcoma; Toxicity Due to Chemotherapy
• Intervention / Treatment: Drug: Triptorelin (GnRHa) + Chemotherapy

Detailed Description

This is a French, Prospective, Multicentre, Open, Randomised study To determine the efficacy of a temporary ovarian suppression obtained by administration of a Gonadotropin Releasing Hormone agonist (GnRHa) on maintaining ovarian reserve, patients will be randomized, half of them receiving Triptorelin extended release (LP) 3 mg intramuscularly every 28±3 days, starting at the inclusion visit and at least 72 days before chemotherapy with alkylating agents until 1 month after end of chemotherapy (mean duration: 12 months).

The primary objective of the study is to determine the effect of a temporary ovarian suppression achieved through administration of a gonadotropin releasing hormone agonist (triptorelin LP 3 mg) during alkylating agents containing chemotherapy on ovarian reserve assessed by AMH serum levels in adolescents and young women with cancer.

Number of centres 19 Research period

• Recruitment duration 2 years
• The duration of participation of each patient is: 3 years
• The duration of the treatment period is: 1 year
• The duration of the follow-up period is: 2 years
• Total duration: 5 years

Statistical analysis:

1. Sample size and design One Hundred and sixty (160) patients will be included in this study in order to ensure at least 128 patients who will complete the study.

   This number of patients should allow us to identify with a power of 80 % a difference of 5 pmol/L in AMH serum levels between the two groups, when accepting a risk alpha of 0.05.

2. Analysis populations The main analysis will be an intention-to-treat (ITT) analysis, which will be performed on all the randomized patients with a value of the main criterion of judgment (AMH level at M24). A per-protocol (PP) analysis will also be performed, as a secondary analysis, excluding patients with major protocol deviation defined a priori.
3. Primary criteria The value of AMH level at month 24will be compared between the two treatment groups using a test t of Student if AMH values are normally distributed and a non-parametric Wilcoxon test if not.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Le Kremlin Bicêtre, France, 94270
    • AP-HP, Bicêtre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female aged 12 to 25 years
• Puberty Tanner 2 or more
• Diagnosis of cancer: Sarcoma, Ewing, Osteosarcoma, Lymphoma
• Chemotherapy protocol with alkylating agents at an intermediate ovarian toxicity risk (Cyclophosphamide 6 g/m2, Ifosfamide 50 g/m2, Procarbazine 4 g/m2, Lomustine 350 mg/m2 or Melphalan 140 mg/m2 or a combination of these drugs).
• All patients with an osteosarcoma, Ewing sarcoma excepted pelvic localisation, Hodgkin lymphoma treatment group III (stages II B, III B and IV), B cell lymphoma group C, rhabdomyosarcoma treated with at least 8 Ifosfamide Vincristin Actinomycin (IVA) courses, synoviosarcoma group II T>5 cm and group III, adult type sarcoma group I and II T>5 cm and group III.
• Before starting any chemotherapy
• Covered by a medical insurance

Exclusion Criteria:

• Prepubertal
• Pregnant
• Planned brain or pelvic radiotherapy
• Planned stem cell transplantation
• Ovariectomy
• Having already received chemotherapy with alkylating agents
• Hypersensitivity to any component of GnRHa

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triptorelin (GnRHa) + Chemotherapy; Triptorelin LP 3 mg (DECAPEPTYL LP 3 mg, IPSEN) 3 mg every 28±3 days, intramuscular during chemotherapy	Drug: Triptorelin (GnRHa) + Chemotherapy; During her chemotherapy, the patient in the experimental arm will have regular injections of Triptorelin (DECAPEPTYL LP 3 mg, IPSEN) in order to preserve her fertility; Other Names: GnRH Agonist injections
No Intervention: Chemotherapy alone; Patient having a chemotherapy without drug injection for fertility preservation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation in AMH serum levels between both groups	Centralised hormonal dosages	at 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with AMH serum levels < 5th percentile in each group		at 24 months
Intra-patient variation in AMH serum levels between groups	Centralised hormonal dosages and study of potential factors associated with the efficacy of GnRHa co-treatment in preventing ovarian reserve loss (if there is one)	up to 36 months
Antral Follicular Count (AFC) on ultrasound between the 2 groups	centralised blind evaluation by an independent reader on compact disc (CD) registration of AFC	at month 24
Delay of resumption of menses between the 2 groups	Comparison of delay of resumption of menses between the 2 groups	up to the end of the follow up (an average of 3 years)
Levels of markers of ovarian reserve: AMH, Follicle-stimulating hormone (FSH), Estradiol between groups	Centralised hormon dosage	at months 12, 24 and 36
Pregnancy rate in the 2 groups		up to the end of the follow up (an average of 3 years)
Adverse events related to Triptorelin co-treatment		up to the end of the follow up (an average of 3 years)
Relative change in Bone Mass Density (BMD) of the lumbar spine, left femoral neck and whole body in the 2 groups	centralised blind evaluation by an independent reader on CD registration of BMD assessed by dual-energy X-ray absorptiometry	at the baseline and at month 12 and month 36

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Cecile THOMAS-TEINTURIER, MD, AP-HP, Bicêtre Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2016
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): February 1, 2021

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: July 31, 2016
• First Posted (Estimate): August 4, 2016

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: GnRH agonist; Ovarian reserve; Alkylating Agents; Fertility Preservation
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Ewing; Osteosarcoma; 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: P140932; 2015-001121-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No