Efficiency of Gonadotropin-releasing Hormone (GnRH) Agonist in Preventing Chemotherapy Induced Ovarian Failure (Erasme-POF)
This study is ongoing, but not recruiting participants.
Sponsor:
Erasme University Hospital
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
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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:
Genetics Home Reference related topics:
Turner syndrome
Drug Information available for:
Norethindrone acetate
Norethindrone
Gonadorelin
Gonadorelin hydrochloride
Deslorelin
Triptorelin pamoate
U.S. FDA Resources
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
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 | |
| Bordet | |
| Brussels, Belgium, 1000 | |
| Erasme Hospital | |
| Brussels, Belgium, 1070 | |
| St Luc University | |
| Brussels, Belgium, 1200 | |
| AZ-VUB | |
| Brussels, Belgium, 1090 | |
| CHRU Lille | |
| Lille, Belgium, 59037 | |
| France | |
| CHU Dijon | |
| Dijon, France, 21034 | |
| CHU Nancy | |
| Nancy, France, 54511 | |
| St Louis Hospital | |
| Paris, France, 75475 | |
| Hôpital Hotel Dieu | |
| Paris, France, 75004 | |
| CHU St Antoine | |
| Paris, France, 75571 | |
| 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 Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Ovarian Diseases Adnexal Diseases Genital Diseases, Female Gonadal Disorders Endocrine System Diseases Norethindrone |
Norethindrone acetate Triptorelin Deslorelin Contraceptives, Oral, Synthetic Contraceptives, Oral Contraceptive Agents, Female Contraceptive Agents Reproductive Control Agents Physiological Effects of Drugs Pharmacologic Actions Therapeutic Uses Luteolytic Agents Antineoplastic Agents, Hormonal Antineoplastic Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013