Ovarian FunctionPhase 4NCT00507780
Effect of Cetrorelex Acetate on Ovarian Function in Women Undergoing Chemotherapy
A Phase 4 study testing GnRH antagonist in people with Ovarian Function and Preservation of Ovarian Function, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
This study will examine whether the drug cetrorelex acetate (Cetrotide[Registed Trademark]) can protect ovarian function in women undergoing chemotherapy. Some cancer treatments are known to cause a change in women's periods or to cause menstruation to stop completely, so that they cannot become pregnant. Read more about this study
- Who is it for?
- Ages 10 to 21 years, women only
- Conditions the study is for
- Ovarian Function, Preservation of Ovarian Function
- What is being tested?
- GnRH antagonist
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jul 2007to 22 Jul 2010
- Phase
- Phase 4
- 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 10 to 21 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- All reproductive age women menarche - age 21, undergoing chemotherapy with agents known to affect ovarian function that have a follicle stimulating hormone level (FSH) less than 20 mIU/L will be offered enrollment. We define premature ovarian failure as the development before age 40 years of greater than 4 months of amenorrhea or menstrual irregularity, associated with two serum FSH levels in the menopausal range (sampled at least 1 mo apart).
Who cannot join
- FSH greater than 20 mIU/L
- Sensitivity or allergy to oral contraceptives (lo ovral) or cetrorelix acetate
- Patients who have had surgical removal of their ovaries
- Patients who are currently pregnant or attempting conception
- Severe renal impairment
- Premenarchal patients
Show all 9Show fewer
- Patients greater than 21
- Patients who have undergone radiation therapy or who are scheduled to undergo radiation therapy during the study period.
- Patients with a family history of premature ovarian failure
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Use of the GnRH Agonist Leuprolide Acetate (Lupron(Registered Trademark)) to Preserve Ovarian Function in Women Undergoing Chemotherapy
This study will examine whether the drug cetrorelex acetate (Cetrotide[Registed Trademark]) can protect ovarian function in women undergoing chemotherapy. Some cancer treatments are known to cause a change in women's periods or to cause menstruation to stop completely, so that they cannot become pregnant. Cetrorelex acetate has been used for many years to lower hormone levels and stop periods in patients undergoing in vitro fertilization treatments. This study will see if making the ovaries inactive may protect them from being affected by certain cancer drugs, and thus preserve fertility.
Women up to age 21who have begun menstruating, who have their uterus and at least one functioning ovary, and who are undergoing chemotherapy with cyclophosphamide, busulfan, nitrogen mustard or L-phenalanin mustard may be eligible for this study.
Read more
Participants undergo the following procedures during this 24-month study:
Baseline evaluation
- Medical history, physical examination and blood and urine tests
- Questionnaire about quality of life, menstrual periods, vaginal bleeding and desire for future fertility
- 3D ultrasound of abdomen
- DEXA scan to evaluate bone density
Assignment to treatment with:
- Lo ovral (contraceptive pill to prevent pregnancy and control menstrual periods) alone, or
- Lo ovral and the study drug cetrorelex acetate, given as an injection under the skin once a day for six menstrual cycles
Evaluations
- Transvaginal 3D ultrasound to monitor changes in the ovary - after 6 months of cetrorelex acetate injections
- DEXA scan - after 6 months of cetrorelex acetate injections
- Blood tests for safety monitoring, pregnancy testing, endocrine tests and research uses - every 3 months during first year, every 6 months during second year
- Questionnaire to monitor changes and quality of life - every 3 months during first year, every 6 months during second year.
Read the detailed description
As a result of the inability of female germ cells to regenerate after injury, a number of chemotherapeutic agents induce premature ovarian failure in the majority of reproductive age women who receive them. The long-term survival for these women has increased with more effective chemotherapies, making iatrogenic ovarian failure and infertility an increasingly significant issue. Currently the choices for maintaining fertility include in vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and the use of GnRH agonist and antagonist to preserve ovarian function.
Much of the evidence for the use of GnRH agonist to prevent premature ovarian failure is found in the systemic lupus erythematosus literature. Blumenfeld and colleagues have published a report that demonstrates preservation of ovarian function in 100% of patients treated with leuprolide acetate prior to cyclophosphamide therapy, compared to a 50% ovarian failure rate in patients not receiving leuprolide acetate. Although the results of animal studies and human studies are encouraging, adequately controlled trials are needed. Future trials will need to have sufficient numbers of patients, receiving multiple types of chemotherapeutic agents to adequately document the utility of medical prophylaxis. The experience with ovulation induction suggests GnRH antagonists may have similar efficacy to GnRH agonists. GnRH antagonists compete directly with GnRH in receptor binding, and as a result antagonists rapidly inhibit secretion of gonadotropin and sex steroids. Unlike GnRH agonists, GnRH antagonists have an immediate effect and antagonists can be given independent of menstrual cycle day. These differences represent several practical benefits offered by an antagonist. In a recent case series by Sauer et al, cetrorelix acetate, a GnRH antagonist, was given in doses of 3mg at four day intervals to four patients ages 21-30. Menses was preserved in all four patients and there was one spontaneous conception. Because of the potential advantages of the use of a GnRH antagonist when compared to an agonist, cetrorelix acetate will be studied against placebo in this investigation.
Our specific aim is to compare the rates of ovarian preservation in reproductive age women receiving chemotherapeutic agents known to affect ovarian function who receive Cetrorelix acetate co treatment with women who receive these agents and do not receive Cetrorelix acetate. A second aim is to evaluate the ability of the Cetrorelix acetate co treatment to induce therapeutic amenorrhea in a study population at risk for thrombocytopenia and associated heavy vaginal bleeding.
- Conditions
- Ovarian Function, Preservation of Ovarian Function
- Being tested
- GnRH antagonist
- Keywords
- GnRH Antagonist, Premature Ovarian Failure, Fertility, Chemotherapy, POF
- Medical subject headings
- Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRH antagonistDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Antimullerian hormone, ovarian follicle count
Measured: 2-years
Secondary outcomes (1)
Menstrual history
Measured: 2-years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2007 (estimated)
- Study start18 Jul 2007
- Primary completion22 Jul 2010
- Study completion22 Jul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ovarian FunctionStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00507780
- Sponsor's protocol ID
- 070193
- Other IDs
- 07-CH-0193
- Status last verified
- 22 Jul 2010
- First submitted
- 26 Jul 2007
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Oktay KH, Yih M. Preliminary experience with orthotopic and heterotopic transplantation of ovarian cortical strips. Semin Reprod Med. 2002 Feb;20(1):63-74. doi: 10.1055/s-2002-23520.
PubMed 11941536Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, Martinez-Madrid B, van Langendonckt A. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004 Oct 16-22;364(9443):1405-10. doi: 10.1016/S0140-6736(04)17222-X.
PubMed 15488215Teinturier C, Hartmann O, Valteau-Couanet D, Benhamou E, Bougneres PF. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure. Bone Marrow Transplant. 1998 Nov;22(10):989-94. doi: 10.1038/sj.bmt.1701483.
PubMed 9849696
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of the GnRH Agonist Leuprolide Acetate (Lupron(Registered Trademark)) to Preserve Ovarian Function in Women Undergoing Chemotherapy
- ClinicalTrials.gov ID
- NCT00507780
- Acronym / sponsor ID
- 070193
- Conditions
- Ovarian Function, Preservation of Ovarian Function
- Keywords
- GnRH Antagonist, Premature Ovarian Failure, Fertility, Chemotherapy, POF
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 18 Jul 2007
- Primary completion
- 22 Jul 2010 (actual)
- Study completion
- 22 Jul 2010 (actual)
- First posted
- 27 Jul 2007 (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.
This study will examine whether the drug cetrorelex acetate (Cetrotide[Registed Trademark]) can protect ovarian function in women undergoing chemotherapy. Some cancer treatments are known to cause a change in women's periods or to cause menstruation to stop completely, so that they cannot become pregnant. Cetrorelex acetate has been used for many years to lower hormone levels and stop periods in patients undergoing in vitro fertilization treatments. This study will see if making the ovaries inactive may protect them from being affected by certain cancer drugs, and thus preserve fertility.
Women up to age 21who have begun menstruating, who have their uterus and at least one functioning ovary, and who are undergoing chemotherapy with cyclophosphamide, busulfan, nitrogen mustard or L-phenalanin mustard may be eligible for this study.
Participants undergo the following procedures during this 24-month study:
Baseline evaluation
- Medical history, physical examination and blood and urine tests
- Questionnaire about quality of life, menstrual periods, vaginal bleeding and desire for future fertility
- 3D ultrasound of abdomen
- DEXA scan to evaluate bone density
Assignment to treatment with:
- Lo ovral (contraceptive pill to prevent pregnancy and control menstrual periods) alone, or
- Lo ovral and the study drug cetrorelex acetate, given as an injection under the skin once a day for six menstrual cycles
Evaluations
- Transvaginal 3D ultrasound to monitor changes in the ovary - after 6 months of cetrorelex acetate injections
- DEXA scan - after 6 months of cetrorelex acetate injections
- Blood tests for safety monitoring, pregnancy testing, endocrine tests and research uses - every 3 months during first year, every 6 months during second year
- Questionnaire to monitor changes and quality of life - every 3 months during first year, every 6 months during second year.
Detailed description
As a result of the inability of female germ cells to regenerate after injury, a number of chemotherapeutic agents induce premature ovarian failure in the majority of reproductive age women who receive them. The long-term survival for these women has increased with more effective chemotherapies, making iatrogenic ovarian failure and infertility an increasingly significant issue. Currently the choices for maintaining fertility include in vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and the use of GnRH agonist and antagonist to preserve ovarian function.
Much of the evidence for the use of GnRH agonist to prevent premature ovarian failure is found in the systemic lupus erythematosus literature. Blumenfeld and colleagues have published a report that demonstrates preservation of ovarian function in 100% of patients treated with leuprolide acetate prior to cyclophosphamide therapy, compared to a 50% ovarian failure rate in patients not receiving leuprolide acetate. Although the results of animal studies and human studies are encouraging, adequately controlled trials are needed. Future trials will need to have sufficient numbers of patients, receiving multiple types of chemotherapeutic agents to adequately document the utility of medical prophylaxis. The experience with ovulation induction suggests GnRH antagonists may have similar efficacy to GnRH agonists. GnRH antagonists compete directly with GnRH in receptor binding, and as a result antagonists rapidly inhibit secretion of gonadotropin and sex steroids. Unlike GnRH agonists, GnRH antagonists have an immediate effect and antagonists can be given independent of menstrual cycle day. These differences represent several practical benefits offered by an antagonist. In a recent case series by Sauer et al, cetrorelix acetate, a GnRH antagonist, was given in doses of 3mg at four day intervals to four patients ages 21-30. Menses was preserved in all four patients and there was one spontaneous conception. Because of the potential advantages of the use of a GnRH antagonist when compared to an agonist, cetrorelix acetate will be studied against placebo in this investigation.
Our specific aim is to compare the rates of ovarian preservation in reproductive age women receiving chemotherapeutic agents known to affect ovarian function who receive Cetrorelix acetate co treatment with women who receive these agents and do not receive Cetrorelix acetate. A second aim is to evaluate the ability of the Cetrorelix acetate co treatment to induce therapeutic amenorrhea in a study population at risk for thrombocytopenia and associated heavy vaginal bleeding.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
Who may qualify
- Ages
- 10 to 21 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- All reproductive age women menarche - age 21, undergoing chemotherapy with agents known to affect ovarian function that have a follicle stimulating hormone level (FSH) less than 20 mIU/L will be offered enrollment. We define premature ovarian failure as the development before age 40 years of greater than 4 months of amenorrhea or menstrual irregularity, associated with two serum FSH levels in the menopausal range (sampled at least 1 mo apart).
Key exclusion criteria (9 listed)
- FSH greater than 20 mIU/L
- Sensitivity or allergy to oral contraceptives (lo ovral) or cetrorelix acetate
- Patients who have had surgical removal of their ovaries
- Patients who are currently pregnant or attempting conception
- Severe renal impairment
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 |
|---|---|---|
| GnRH antagonist | Drug | – |
Primary outcome
Antimullerian hormone, ovarian follicle count
Time frame: 2-years
1 secondary outcome
Menstrual history
Time frame: 2-years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 11941536Oktay KH, Yih M. Preliminary experience with orthotopic and heterotopic transplantation of ovarian cortical strips. Semin Reprod Med. 2002 Feb;20(1):63-74. doi: 10.1055/s-2002-23520.
- Background: PubMed 15488215Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, Martinez-Madrid B, van Langendonckt A. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004 Oct 16-22;364(9443):1405-10. doi: 10.1016/S0140-6736(04)17222-X.
- Background: PubMed 9849696Teinturier C, Hartmann O, Valteau-Couanet D, Benhamou E, Bougneres PF. Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure. Bone Marrow Transplant. 1998 Nov;22(10):989-94. doi: 10.1038/sj.bmt.1701483.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing GnRH antagonist in people with Ovarian Function and Preservation of Ovarian Function, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
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 1 inclusion and 9 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: withdrawn, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Antimullerian hormone, ovarian follicle count (time frame: 2-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 NCT00507780, which also lists 3 linked publications.
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 2 Jul 2017.