Fertility PreservationPhase 2/3Erasme-POFNCT01160315
Efficiency of Gonadotropin-releasing Hormone (GnRH) Agonist in Preventing Chemotherapy Induced Ovarian Failure
A Phase 2/3 study testing Triptorelin and Norethisterone acetate in people with Fertility Preservation and Alkylating Agents, run by Erasme University Hospital at 15 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Fertility Preservation, Alkylating Agents, Lymphoma
- What is being tested?
- Triptorelin and Norethisterone acetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 15 sitesin 3 countries
- Study dates
- Jul 2002to Oct 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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 locations and contacts
15 sites in 3 countries.
15 sites in 3 countries
Belgium7 sites
Algemeen Ziekenhuis Stuivenberg
Antwerp, 2060
AZ St Jan
Brugges, 8000
Bordet
Brussels, 1000
Erasme Hospital
Brussels, 1070
AZ-VUB
Brussels, 1090
St Luc University
Brussels, 1200
CHRU Lille
Lille, 59037
France7 sites
CHU Dijon
Dijon, 21034
CHU Nancy
Nancy, 54511
Hôpital Hotel Dieu
Paris, 75004
St Louis Hospital
Paris, 75475
CHU St Antoine
Paris, 75571
Henry-Mondor Hospital
Paris-Creteil, 94010
Centre Henri Beckerel
Rouen, 76038
About this study
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.
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.
- Conditions
- Fertility Preservation, Alkylating Agents, Lymphoma
- Being tested
- Triptorelin, Norethisterone acetate
- Keywords
- ovarian failure, chemotherapy, lymphoma, GnRH agonist
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriptorelinDrug
Also called Decapeptyl
Triptorelin: intramusculAR injection every 3 months
Norethisterone acetateDrug
Also called Primolut
5 mg/day per os until during chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Triptorelin; Drug: Norethisterone acetate |
| Arm B (control Arm) | Active comparator | Norethisterone acetate alone, 5mg par day, (ARM B) until the end of the chemotherapy. Receives: Drug: Norethisterone acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years
Secondary outcomes (4)
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.
Measured: 2 years
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.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2010 (estimated)
- Study startJul 2002
- Primary completionJun 2010
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fertility PreservationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasme University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fonds National de la Recherche Scientifique, Ipsen
- Responsible party
- Sponsor
- Investigators
- Yvon Englert, MD, PhD, Study director, Erasme University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01160315
- Sponsor's protocol ID
- ErasmeUH
- Acronym
- Erasme-POF
- Status last verified
- Oct 2015
- First submitted
- 7 Jul 2010
- Last updated
- 30 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23129737
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01160315
- Acronym / sponsor ID
- Erasme-POF / ErasmeUH
- Conditions
- Fertility Preservation, Alkylating Agents, Lymphoma
- Keywords
- ovarian failure, chemotherapy, lymphoma, GnRH agonist
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Erasme University HospitalUniversity, hospital or other
- Collaborators
- Fonds National de la Recherche Scientifique, Ipsen
- Study start
- Jul 2002
- Primary completion
- Jun 2010 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 12 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (GnRha arm) | Experimental | Drug: Triptorelin, Drug: Norethisterone acetateIM 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 |
| Arm B (control Arm) | Active comparator | Drug: Norethisterone acetateNorethisterone acetate alone, 5mg par day, (ARM B) until the end of the chemotherapy. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TriptorelinAlso: DecapeptylTriptorelin: intramusculAR injection every 3 months | Drug | Arm A (GnRha arm) |
| Norethisterone acetateAlso: Primolut5 mg/day per os until during chemotherapy | Drug | Arm A (GnRha arm), Arm B (control Arm) |
Primary outcome
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.
4 secondary outcomes
Impact of the flare-up effect of Triptorelin
Time frame: 2 years
Ovarian function during the treatment
Time frame: 1 year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 1 year
Add back therapy effect
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2015.
- Derived from this study: PubMed 23129737Demeestere 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yvon Englert, MD, PhD study director
Erasme University Hospital
15 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Triptorelin and Norethisterone acetate in people with Fertility Preservation and Alkylating Agents, run by Erasme University Hospital at 15 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Belgium, France, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Premature ovarian failure rate (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01160315, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2015.