Clinical trial NCT02856048: Co-treatment With GnRH Analogs on the Ovarian Reserve in Young Women Treated With Alkylating Agents for Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Cancer
Toxicity Due to Chemotherapy
Sarcoma
Osteosarcoma
Lymphoma
Ewing Sarcoma
Keywords: GnRH agonist
Ovarian reserve
Fertility Preservation
Alkylating Agents
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2016-08-04
Enrollment: 11
Sex: FEMALE
Minimum age (years): 12
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Variation in AMH serum levels between both groups
timeFrame: at 24 months
Secondary outcomes:
measure: Number of patients with AMH serum levels < 5th percentile in each group
timeFrame: at 24 months
measure: Intra-patient variation in AMH serum levels between groups
timeFrame: up to 36 months
measure: Antral Follicular Count (AFC) on ultrasound between the 2 groups
timeFrame: at month 24
measure: Delay of resumption of menses between the 2 groups
timeFrame: up to the end of the follow up (an average of 3 years)
measure: Levels of markers of ovarian reserve: AMH, Follicle-stimulating hormone (FSH), Estradiol between groups
timeFrame: at months 12, 24 and 36
measure: Pregnancy rate in the 2 groups
timeFrame: up to the end of the follow up (an average of 3 years)
measure: Adverse events related to Triptorelin co-treatment
timeFrame: up to the end of the follow up (an average of 3 years)
measure: Relative change in Bone Mass Density (BMD) of the lumbar spine, left femoral neck and whole body in the 2 groups
timeFrame: at the baseline and at month 12 and month 36
Other outcomes:
Locations:
city: Le Kremlin Bicêtre
country: France
facility: AP-HP, Bicêtre Hospital
Study officials:
affiliation: AP-HP, Bicêtre Hospital
name: Cecile THOMAS-TEINTURIER, MD
role: PRINCIPAL_INVESTIGATOR
References: