Efficiency of Gonadotropin-releasing Hormone (GnRH) Agonist in Preventing Chemotherapy Induced Ovarian Failure (Erasme-POF)
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|ClinicalTrials.gov Identifier: NCT01160315|
Recruitment Status : Completed
First Posted : July 12, 2010
Last Update Posted : October 30, 2015
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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||118 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Primary Completion Date :||June 2010|
|Study Completion Date :||October 2015|
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
Triptorelin: intramusculAR injection every 3 months
Other Name: DecapeptylDrug: 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
- 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.
- 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.
- 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.
- 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.
- 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.
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): NCT01160315
|Algemeen Ziekenhuis Stuivenberg|
|Antwerpen, Belgium, 2060|
|AZ St Jan|
|Brugges, Belgium, 8000|
|Brussels, Belgium, 1000|
|Brussels, Belgium, 1070|
|Brussels, Belgium, 1090|
|St Luc University|
|Brussels, Belgium, 1200|
|Lille, Belgium, 59037|
|Dijon, France, 21034|
|Nancy, France, 54511|
|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|
|Study Director:||Yvon Englert, MD, PhD||Erasme Hospital|