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

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ClinicalTrials.gov Identifier: NCT02856048
Recruitment Status : Active, not recruiting
First Posted : August 4, 2016
Last Update Posted : February 27, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Cancer Toxicity Due to Chemotherapy Sarcoma Osteosarcoma Lymphoma Ewing Sarcoma Drug: Triptorelin (GnRHa) + Chemotherapy Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2016
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021


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 Name: GnRH Agonist injections

No Intervention: Chemotherapy alone
Patient having a chemotherapy without drug injection for fertility preservation



Primary Outcome Measures :
  1. Variation in AMH serum levels between both groups [ Time Frame: at 24 months ]
    Centralised hormonal dosages


Secondary Outcome Measures :
  1. Number of patients with AMH serum levels < 5th percentile in each group [ Time Frame: at 24 months ]
  2. Intra-patient variation in AMH serum levels between groups [ Time Frame: 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)

  3. Antral Follicular Count (AFC) on ultrasound between the 2 groups [ Time Frame: at month 24 ]
    centralised blind evaluation by an independent reader on compact disc (CD) registration of AFC

  4. Delay of resumption of menses between the 2 groups [ Time Frame: up to the end of the follow up (an average of 3 years) ]
    Comparison of delay of resumption of menses between the 2 groups

  5. Levels of markers of ovarian reserve: AMH, Follicle-stimulating hormone (FSH), Estradiol between groups [ Time Frame: at months 12, 24 and 36 ]
    Centralised hormon dosage

  6. Pregnancy rate in the 2 groups [ Time Frame: up to the end of the follow up (an average of 3 years) ]
  7. Adverse events related to Triptorelin co-treatment [ Time Frame: up to the end of the follow up (an average of 3 years) ]
  8. Relative change in Bone Mass Density (BMD) of the lumbar spine, left femoral neck and whole body in the 2 groups [ Time Frame: 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



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Ages Eligible for Study:   12 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02856048


Locations
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France
AP-HP, Bicêtre Hospital
Le Kremlin Bicêtre, France, 94270
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Cecile THOMAS-TEINTURIER, MD AP-HP, Bicêtre Hospital

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02856048     History of Changes
Other Study ID Numbers: P140932
2015-001121-17 ( EudraCT Number )
First Posted: August 4, 2016    Key Record Dates
Last Update Posted: February 27, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
GnRH agonist
Ovarian reserve
Fertility Preservation
Alkylating Agents
Additional relevant MeSH terms:
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Sarcoma
Osteosarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Triptorelin Pamoate
Deslorelin
Alkylating Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents