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

Cancer Clinical Trial

— PRESOV  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02856048
• Other study ID #: P140932
• Secondary ID: 2015-001121-17
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: November 23, 2016
• Est. completion date: February 2021

Study information

• Verified date: December 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 12 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Ewing Sarcoma
• Lymphoma
• Osteosarcoma
• Sarcoma
• Sarcoma, Ewing
• Toxicity Due to Chemotherapy

Intervention

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

Locations

Country	Name	City	State
France	AP-HP, Bicêtre Hospital	Le Kremlin Bicêtre

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Variation in AMH serum levels between both groups	Centralised hormonal dosages	at 24 months
Secondary	Number of patients with AMH serum levels < 5th percentile in each group		at 24 months
Secondary	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
Secondary	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
Secondary	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)
Secondary	Levels of markers of ovarian reserve: AMH, Follicle-stimulating hormone (FSH), Estradiol between groups	Centralised hormon dosage	at months 12, 24 and 36
Secondary	Pregnancy rate in the 2 groups		up to the end of the follow up (an average of 3 years)
Secondary	Adverse events related to Triptorelin co-treatment		up to the end of the follow up (an average of 3 years)
Secondary	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