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

Lymphoma Clinical Trial

— Erasme-POF  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01160315
• Other study ID #: ErasmeUH
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 7, 2010
• Last updated: October 29, 2015
• Start date: July 2002
• Est. completion date: October 2015

Study information

• Verified date: October 2015
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics CommitteeFrance: Institutional Ethical CommitteeItaly: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: October 2015
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Alkylating Agents
• Fertility Preservation
• Lymphoma

Intervention

Drug:
• Triptorelin
Triptorelin: intramusculAR injection every 3 months
• Norethisterone acetate
5 mg/day per os until during chemotherapy

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Stuivenberg	Antwerpen
Belgium	AZ St Jan	Brugges
Belgium	AZ-VUB	Brussels
Belgium	Bordet	Brussels
Belgium	Erasme Hospital	Brussels
Belgium	St Luc University	Brussels
Belgium	CHRU Lille	Lille
France	CHU Dijon	Dijon
France	CHU Nancy	Nancy
France	CHU St Antoine	Paris
France	Hôpital Hotel Dieu	Paris
France	St Louis Hospital	Paris
France	Henry-Mondor Hospital	Paris-Creteil
France	Centre Henri Beckerel	Rouen
Italy	Instituto Europeo di oncologia	Milano

Sponsors (3)

Lead Sponsor	Collaborator
Erasme University Hospital	Fonds National de la Recherche Scientifique, Ipsen

Countries where clinical trial is conducted

Belgium,  France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Premature ovarian failure rate	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	No
Secondary	Impact of the flare-up effect of Triptorelin	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	No
Secondary	Ovarian function during the treatment	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	No
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	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	Yes
Secondary	Add back therapy effect	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	Yes