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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01160315
Recruitment Status : Completed
First Posted : July 12, 2010
Last Update Posted : October 30, 2015
Fonds National de la Recherche Scientifique
Information provided by (Responsible Party):
Erasme University Hospital

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Fertility Preservation Alkylating Agents Lymphoma Drug: Triptorelin Drug: Norethisterone acetate Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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.
Study Start Date : July 2002
Actual Primary Completion Date : June 2010
Actual Study Completion Date : October 2015

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 Name: Decapeptyl

Drug: Norethisterone acetate
5 mg/day per os until during chemotherapy
Other Name: 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 Name: Primolut

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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. 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.

  3. 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.

  4. 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.

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT01160315

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Algemeen Ziekenhuis Stuivenberg
Antwerpen, Belgium, 2060
AZ St Jan
Brugges, Belgium, 8000
Brussels, Belgium, 1000
Erasme Hospital
Brussels, Belgium, 1070
Brussels, Belgium, 1090
St Luc University
Brussels, Belgium, 1200
CHRU Lille
Lille, Belgium, 59037
CHU Dijon
Dijon, France, 21034
CHU Nancy
Nancy, France, 54511
Henry-Mondor Hospital
Paris-Creteil, France, 94010
Hôpital Hotel Dieu
Paris, France, 75004
St Louis Hospital
Paris, France, 75475
CHU St Antoine
Paris, France, 75571
Centre Henri Beckerel
Rouen, France, 76038
Instituto Europeo di oncologia
Milano, Italy, 1-20141
Sponsors and Collaborators
Erasme University Hospital
Fonds National de la Recherche Scientifique
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Study Director: Yvon Englert, MD, PhD Erasme Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Erasme University Hospital Identifier: NCT01160315     History of Changes
Other Study ID Numbers: ErasmeUH
First Posted: July 12, 2010    Key Record Dates
Last Update Posted: October 30, 2015
Last Verified: October 2015

Keywords provided by Erasme University Hospital:
ovarian failure, chemotherapy, lymphoma, GnRH agonist

Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Triptorelin Pamoate
Norethindrone Acetate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral