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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Fonds National de la Recherche Scientifique
Ipsen
Information provided by:
Erasme University Hospital
ClinicalTrials.gov Identifier:
NCT01160315
First received: July 7, 2010
Last updated: July 30, 2010
Last verified: July 2010
  Purpose

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 Intervention Phase
Ovarian Function Restoration After Chemotherapy for Lymphoma
Drug: GnRH agonist (triptorelin)+ Norethisterone acetate
Drug: Norethisterone acetate
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Erasme University Hospital:

Primary Outcome Measures:
  • Premature ovarian failure rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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:
  • Impact of the flare-up effect of Triptorelin [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The Triptorelin/Noretistherone 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/norestistherone 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.

  • Ovarian function during the treatment [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • Add back therapy effect [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 118
Study Start Date: July 2002
Estimated Study Completion Date: June 2017
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (GnRha arm)
IM injection of Triptorelin -Décapeptyl PR 11.25mg- (every 3 months) and Norethisterone acetate- Primolut-Nor 5 mg- per os continuously until the end of the chemotherapy
Drug: GnRH agonist (triptorelin)+ Norethisterone acetate
Triptorelin:intramusculAR injection every 3 months Noresthistherone acetate 5 mg/day Until the en of the chemotherapy
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

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160315

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

No publications provided by Erasme University Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Englert Yvon, Erasme Hospital
ClinicalTrials.gov Identifier: NCT01160315     History of Changes
Other Study ID Numbers: ErasmeUH
Study First Received: July 7, 2010
Last Updated: July 30, 2010
Health Authority: Belgium: Ethics Committee
France: Institutional Ethical Committee
Italy: Ethics Committee

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

Additional relevant MeSH terms:
Lymphoma
Menopause, Premature
Primary Ovarian Insufficiency
Adnexal Diseases
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Ovarian Diseases
Deslorelin
Norethindrone
Norethindrone acetate
Triptorelin Pamoate
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Enzyme Inhibitors
Luteolytic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents

ClinicalTrials.gov processed this record on November 24, 2014