Efficiency of Gonadotropin-releasing Hormone (GnRH) Agonist in Preventing Chemotherapy Induced Ovarian Failure (Erasme-POF)

October 29, 2015 updated by: Erasme University Hospital

A Prospective Open Randomized Trial on the Efficacy of Gonadotropin-releasing Hormone Agonist Depot-Triptorelin- to Prevent Chemotherapy Induced Premature Ovarian Failure in Lymphoma Patients.

Chemotherapy drugs like alkylating agents are frequently used in various combined regimens to treat neoplastic and benign diseases. These drugs are definitely associated with premature ovarian failure (POF), resulting in an important decrease of the long-term quality of life and an increase of morbidity. A recent study showed that the patients treated by alkylating agents had a 4.52 fold higher risk to lose their ovarian function compared with those who were treated by other agents. The rate of POF after treatment ranged from 40 to 80%, according to the age of the patients and the total doses administered.

Young women who experience POF have to face with the prospects of infertility and to consider years of hormonal replacement therapy. The possibility of minimizing gonadal damage by administering of protective therapy during chemotherapy represents an attractive option for these patients.

The aim of this study is to evaluate the protective effect on the ovarian function of the gonadotropin-releasing hormone agonist (GnRha) administered concomitantly to alkylating agents. Preliminary data in the literature on animals (rat and monkeys) are promising. Data in human are, however, highly controversial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

118

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium, 2060
        • Algemeen Ziekenhuis Stuivenberg
      • Brugges, Belgium, 8000
        • AZ St Jan
      • Brussels, Belgium, 1070
        • Erasme hospital
      • Brussels, Belgium, 1090
        • AZ-VUB
      • Brussels, Belgium, 1000
        • Bordet
      • Brussels, Belgium, 1200
        • St Luc University
      • Lille, Belgium, 59037
        • CHRU Lille
  • France
      • Dijon, France, 21034
        • CHU Dijon
      • Nancy, France, 54511
        • CHU Nancy
      • Paris, France, 75004
        • Hôpital Hotel Dieu
      • Paris, France, 75475
        • St Louis Hospital
      • Paris, France, 75571
        • CHU St Antoine
      • Paris-Creteil, France, 94010
        • Henry-Mondor Hospital
      • Rouen, France, 76038
        • Centre Henri Beckerel
  • Italy
      • Milano, Italy, 1-20141
        • Instituto Europeo di Oncologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women between 18 and 45 years old with lymphoma.
  • Menarche >2year
  • Subject treated by chemotherapy-induced ovarian failure including alkylant agents (except less than 8 ABVD)
  • Presence of both ovaries (ovarian biopsy or hemiovariectomy for cryopreservation before treatment is accepted).
  • Ability to give written informed consent

Exclusion Criteria:

  • Hormonal-sensible malignancy
  • Chemotherapy or radiotherapy before the inclusion in the study
  • Pelvic irradiation including the ovaries or TBI
  • Pregnancy
  • Patient weight above 110 kg
  • Anamnesis of thrombo-embolic processes
  • Severe hepatic or renal insufficiency
  • Systolic blood pressure >15mmHg or diastolic blood pressure > 90mmHg
  • Contraindication of IM injection
  • Relevant ovarian abnormalities (Functional follicular cyst are tolerated)
  • Anamnesis of premature ovarian failure or irregular cycle (repeated amenorrhoea >2 months)
  • Dubin-Johnson and Rotor Syndrome

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (GnRha arm)
IM injection of Triptorelin -Decapeptyl PR 11.25mg- (every 3 months) and Norethisterone acetate- Primolut-Nor 5 mg- per os continuously until the end of the chemotherapy
Drug: Triptorelin
Triptorelin: intramusculAR injection every 3 months
Other Names:
  • Decapeptyl
Drug: Norethisterone acetate
5 mg/day per os until during chemotherapy
Other Names:
  • Primolut
Active Comparator: Arm B (control Arm)
Norethisterone acetate alone, 5mg par day, (ARM B) until the end of the chemotherapy.
Drug: Norethisterone acetate
5 mg/day per os until during chemotherapy
Other Names:
  • Primolut

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Premature ovarian failure rate
Time Frame: 5 years
Primary endpoint is to evaluate the short and long-term efficacy of triptorelin depot plus progestin versus progestin alone to prevent POF induced by chemotherapy treatment. The ovarian function (FSH, E2, Progesterone, and AMH, presence of spontaneous menstrual cycle and pregnancies) will be evaluated every 3 months during the first 6 months after the end of chemotherapy, every 6 months during the next 18 months and once a year during an additional 5 years. All hormonal treatment has to be interrupted 10 days before the blood test.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of the flare-up effect of Triptorelin
Time Frame: 2 years
The Triptorelin/Norethisterone treatment has to start if possible 10 days before the beginning of the chemotherapy (time necessary to obtain the inhibitory effect of the Gn-Rha on the ovarian function)and at least the same day. The impact of the interval between the triptorelin/noresthisterone treatment and the start of the chemotherapy on the efficacy to protect ovarian function (FSH level at 2 years of follow-up) will be evaluated.
2 years
Ovarian function during the treatment
Time Frame: 1 year
Evaluation of the inhibitory action of the treatment on ovarian function during the chemotherapy: the hormonal profile (FSH and estradiol levels) will be evaluated 10 days after the triptorelin/Norethisterone treatment start, before the second injection (3 months) and at the end of the chemotherapy. Adverse effects due to the injection are evaluated 7-10 days after each injection.
1 year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 1 year
Anamnesis including the compliance of the treatment (possible treatment interruption or dosage modification) and the adverse events are performed at each visit. All events expected and directly related to the chemotherapy or the initial pathology will be documented in the Case Report Form adverse events. Specific anamnesis concerning the possible adverse events due to treatment must be completed for each follow-up visit.
1 year
Add back therapy effect
Time Frame: 1 year
Evaluation of the efficacy of concomitant administration of progestin alone as "Add Back Therapy" during the treatment: specific anamnesis including estrogen-deficiency symptoms (hot flushes, vaginal dryness...) is reported at each visit during the treatment. Osteodensitometry is performed after 1 year follow-up.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Erasme University Hospital

Collaborators

Ipsen
Fonds National de la Recherche Scientifique

Investigators

  • Study Director: Yvon Englert, MD, PhD, Erasme hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2002

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

July 7, 2010

First Submitted That Met QC Criteria

July 9, 2010

First Posted (Estimate)

July 12, 2010

Study Record Updates

Last Update Posted (Estimate)

October 30, 2015

Last Update Submitted That Met QC Criteria

October 29, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ErasmeUH

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on Triptorelin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Albania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe