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

Phase 2

• Conditions: Toxicity Due to Chemotherapy; Sarcoma; Osteosarcoma; Cancer; Lymphoma; Ewing Sarcoma
• Interventions: Drug: Triptorelin (GnRHa) + Chemotherapy

• Registration Number: NCT02856048
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief 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.

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 Timeline

• Study First Submitted: 2016-07-19
• Study First Submitted QC: 2016-07-31
• Study First Posted: 2016-08-04
• Study Start: 2016-11-23
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-16
• Last Update Posted: 2019-12-17
• Primary Completion: 2021-02
• Study Completion: 2021-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 11

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Triptorelin (GnRHa) + Chemotherapy	Triptorelin (GnRHa) + Chemotherapy	Triptorelin LP 3 mg (DECAPEPTYL LP 3 mg, IPSEN) 3 mg every 28±3 days, intramuscular during chemotherapy

Primary Outcome Measures

Name	Time	Method
Variation in AMH serum levels between both groups	at 24 months	Centralised hormonal dosages

Secondary Outcome Measures

Name	Time	Method
Number of patients with AMH serum levels < 5th percentile in each group	at 24 months
Intra-patient variation in AMH serum levels between groups	up to 36 months	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)
Antral Follicular Count (AFC) on ultrasound between the 2 groups	at month 24	centralised blind evaluation by an independent reader on compact disc (CD) registration of AFC
Relative change in Bone Mass Density (BMD) of the lumbar spine, left femoral neck and whole body in the 2 groups	at the baseline and at month 12 and month 36	centralised blind evaluation by an independent reader on CD registration of BMD assessed by dual-energy X-ray absorptiometry
Levels of markers of ovarian reserve: AMH, Follicle-stimulating hormone (FSH), Estradiol between groups	at months 12, 24 and 36	Centralised hormon dosage
Delay of resumption of menses between the 2 groups	up to the end of the follow up (an average of 3 years)	Comparison of delay of resumption of menses between the 2 groups
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)

Trial Locations

Locations (1)

AP-HP, Bicêtre Hospital; 🇫🇷 Le Kremlin Bicêtre, France