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

Free University of Brussels (ULB)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Lymphoma; Fertility Preservation; Alkylating Agents

Treatments: Drug: Norethisterone acetate; Drug: Triptorelin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01160315

ErasmeUH

Details and patient eligibility

About

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.

Enrollment: 118 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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118 participants in 2 patient groups

Arm A (GnRha arm)

Experimental group

Description:

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

Treatment:

Drug: Triptorelin

Drug: Norethisterone acetate

Arm B (control Arm)

Active Comparator group

Description:

Norethisterone acetate alone, 5mg par day, (ARM B) until the end of the chemotherapy.

Treatment:

Drug: Norethisterone acetate