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

Study Overview
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Brief Summary
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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
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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: 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. 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. 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.

Official Title
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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

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

Intervention / Treatment
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* Drug: Triptorelin (GnRHa) + Chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triptorelin (GnRHa) + Chemotherapy<br>Triptorelin LP 3 mg (DECAPEPTYL LP 3 mg, IPSEN) 3 mg every 28±3 days, intramuscular during chemotherapy | Drug: Triptorelin (GnRHa) + Chemotherapy<br>* 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<br>* Other names: GnRH Agonist injections;|
| No Intervention: Chemotherapy alone<br>Patient having a chemotherapy without drug injection for fertility preservation | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GnRH agonist, Ovarian reserve, Fertility Preservation, Alkylating Agents