NCT01160315

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
118

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jul 2002

Longer than P75 for phase_2

Geographic Reach
3 countries

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2002

Completed
7.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2010

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

July 7, 2010

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 12, 2010

Completed
5.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
Last Updated

October 30, 2015

Status Verified

October 1, 2015

Enrollment Period

7.9 years

First QC Date

July 7, 2010

Last Update Submit

October 29, 2015

Conditions

Fertility PreservationAlkylating AgentsLymphoma

Keywords

ovarian failure, chemotherapy, lymphoma, GnRH agonist

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (4)

  • Impact of the flare-up effect of Triptorelin

    2 years

  • Ovarian function during the treatment

    1 year

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    1 year

  • Add back therapy effect

    1 year

Study Arms (2)

Arm A (GnRha arm)

EXPERIMENTAL

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

Drug: TriptorelinDrug: Norethisterone acetate

Arm B (control Arm)

ACTIVE COMPARATOR

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

Drug: Norethisterone acetate

Interventions

TriptorelinDRUG

Triptorelin: intramusculAR injection every 3 months

Also known as: Decapeptyl
Arm A (GnRha arm)
Norethisterone acetateDRUG

5 mg/day per os until during chemotherapy

Also known as: Primolut
Arm A (GnRha arm)Arm B (control Arm)

Eligibility Criteria

Age18 Years - 45 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • Hormonal-sensible malignancy
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Algemeen Ziekenhuis Stuivenberg

Antwerp, 2060, Belgium

Location

AZ St Jan

Brugges, 8000, Belgium

Location

Bordet

Brussels, 1000, Belgium

Location

Erasme Hospital

Brussels, 1070, Belgium

Location

AZ-VUB

Brussels, 1090, Belgium

Location

St Luc University

Brussels, 1200, Belgium

Location

CHRU Lille

Lille, 59037, Belgium

Location

CHU Dijon

Dijon, 21034, France

Location

CHU Nancy

Nancy, 54511, France

Location

Hôpital Hotel Dieu

Paris, 75004, France

Location

St Louis Hospital

Paris, 75475, France

Location

CHU St Antoine

Paris, 75571, France

Location

Henry-Mondor Hospital

Paris-Creteil, 94010, France

Location

Centre Henri Beckerel

Rouen, 76038, France

Location

Instituto Europeo di oncologia

Milan, 1-20141, Italy

Location

Related Publications (1)

  • Demeestere I, Brice P, Peccatori FA, Kentos A, Gaillard I, Zachee P, Casasnovas RO, Van Den Neste E, Dechene J, De Maertelaer V, Bron D, Englert Y. Gonadotropin-releasing hormone agonist for the prevention of chemotherapy-induced ovarian failure in patients with lymphoma: 1-year follow-up of a prospective randomized trial. J Clin Oncol. 2013 Mar 1;31(7):903-9. doi: 10.1200/JCO.2012.42.8185. Epub 2012 Nov 5.

    PMID: 23129737DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

Triptorelin PamoateNorethindrone Acetate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing HormonePituitary Hormone-Releasing HormonesHypothalamic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNeuropeptidesPeptidesAmino Acids, Peptides, and ProteinsOligopeptidesNerve Tissue ProteinsProteinsNorethindroneNorpregnenesNorpregnanesNorsteroidsSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Yvon Englert, MD, PhD

    Erasme University Hospital

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 7, 2010

First Posted

July 12, 2010

Study Start

July 1, 2002

Primary Completion

June 1, 2010

Study Completion

October 1, 2015

Last Updated

October 30, 2015

Record last verified: 2015-10

Locations

FR(7)BE(7)IT(1)