Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03947151 |
| Other study ID # |
P170407J |
| Secondary ID |
2018-000049-38 |
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
November 28, 2019 |
| Est. completion date |
August 30, 2022 |
Study information
| Verified date |
September 2022 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The present investigation aims to evaluate the efficacy of an innovative protocol of
controlled ovarian stimulation for breast cancer patients, who are candidates for fertility
preservation.
Currently, vitrification of oocytes and/or embryos after controlled ovarian stimulation is
the most established method for female fertility preservation. However, this stimulation
induces an increase in serum estrogen levels, which is theoretically problematic in case of
hormone-sensitive tumors such as breast cancer. The majority of oncology teams accept, in
very specific situations (particularly when the tumor has been surgically removed), this
ovarian stimulation, because the expected benefits of fertility preservation far outweigh the
risks. However, everyone agrees that it would be more comfortable to be able to offer
vitrification of oocytes and/or embryos using ovarian stimulation without increasing estrogen
levels.
In this research, investigators will evaluate the efficacy of degarelix (Firmagon®),
currently indicated for the treatment of prostate cancer, as an innovative ovarian
stimulation procedure. Administered at the beginning of ovarian stimulation, they believe it
should maintain serum estradiol levels at physiological values at the end of stimulation.
Description:
Recent improvements in freezing techniques have led to the development of fertility
preservation techniques for young women diagnosed with cancer. Currently, vitrification of
oocytes or embryos after controlled ovarian stimulation (COS) represents the only established
method. This COS is based on the daily administration of exogenous Follicle Stimulating
Hormone (FSH) and an ovulation blockage using Gonadotropin Releasing Hormone (GnRH)
antagonists (0.25 mg/d) initiated after approximately 6 days of stimulation and continued
until ovulation is triggered.
In addition to requiring 15 days, COS induces supraphysiological hyperestradiolaemia (5-10
times normal) which can be problematic in case of hormone-sensitive tumors such as breast
cancer. The majority of oncology teams accept, in very specific situations (particularly when
the tumor has been surgically removed), this ovarian stimulation, because the expected
benefits of fertility preservation far outweigh the risks. However, everyone agrees that it
would be more comfortable to be able to offer vitrification of oocytes and/or embryos using
ovarian stimulation without increasing estrogen levels.
Therefore, the limitation of serum estradiol concentrations during stimulation represents an
important issue. To this end, stimulation protocols combining aromatase inhibitors have been
proposed. Inhibition of the P450 aromatase enzyme in the granulosa cells of stimulated
follicles prevents the conversion of androgens to estrogens. However, the teratogenic risk of
these molecules, although discussed, limits their use in the indication of COS. Recently, a
new "natos" protocol was proposed to stimulate the ovaries while maintaining physiological
estradiolaemia, without using aromatase inhibitors. Thus, the administration of high doses of
Gonadotropin Releasing Hormone (GnRH) antagonists (3 to 6 injections of 0.25 mg/day) from the
beginning of COS, would allow a strong Luteinizing Hormone (LH) deprivation, thus limiting
the production of androgens according to the 2 cells - 2 gonadotropins theory. In the absence
of a precursor, estradiolemia remains at physiological ranges during the total duration of
COS. However, the relative heaviness of a protocol combining up to 8 daily injections limits
its use in young women who are candidates for fertility preservation.
Investigators therefore propose to evaluate the efficacy and tolerance of a new natos-like
COS protocol based on the administration of a long-acting GnRH antagonist, degarelix. This
drug is currently off-label for women.
The expected duration of the research is 14 months and participation will be 2 months.
After signature of the consent, during the first visit (oncofertility counseling), the the
research (consultations and examinations) will be carried out within the Antoine Béclère
hospital. All visits and examinations performed are part of routine care, except for the
injection(s) of degarelix which belongs to the research.
Inclusion visit During the oncofertility consultation, the physician will make sure that the
patient can be included in the research. Once the consent has been signed, the doctor will
schedule the following visits based on the biological results obtained as part of the usual
care.
Research follow-up visits
Stimulation: between the day of oncofertility counseling and the following 7 days, the doctor
will check that patients are in the early follicular phase of the cycle, Degarelix injection:
1 injection, under the skin (possibly renewable after 5-7 days if the serum LH is ≥2 IU / L
and / or the estradiol is ≥400 pg / mL), Concomitant initiation of ovarian stimulation by
administration of recombinant FSH - Follitropin alfa (usual care). The injections will be
given by the patient or a nurse at home, between 7pm and 10pm.
Stimulation follow-up visit #1 :
After 5 days of ovarian stimulation, transvaginal pelvic ultrasound (counting of ovarian
follicles and measurement of their diameters) and blood sampling for serum hormone assays
(estradiol, LH, progesterone) will be performed as part of the usual care.
Stimulation follow-up visits #2 and #3 Visits #2 and #3: transvaginal pelvic ultrasound
(counting of ovarian follicles and measurement of their diameters) and a blood test for serum
hormone assays (estradiol, LH, progesterone) will be required to monitor the response to
stimulation, as part of routine care.
Visits are repeated until 4 follicles 16 to 20 mm in diameter are obtained, which is the
criterion for ovulation trigger using 1 injection of Human Chorionic Gonadotropin (hCG)
(Ovitrelle 250 mcg, SC) (usual care). Thus visits #2 and #3 are systematic. One or two
additional visits with the same examinations may sometimes be necessary if the trigger
criteria are not met.
Thirty-six hours after Human Chorionic Gonadotropin (hCG) , oocyte retrieval will be
performed.
Visit on the day of the oocyte retrieval:
Patients will have a venous blood sample for serum hormone assays (estradiol, LH,
progesterone) as part of the usual care.
Oocyte collection will be scheduled, and those which are mature will then be frozen (by
vitrification) or fertilized in vitro in case of embryo freezing.
Visit following egg retrieval:
A blood test for serum hormone assays (estradiol, LH, progesterone) will be performed 3-4
days after oocyte retrieval.
End of research visit Participants will be contacted by phone 2 months after the injection of
degarelix (Firmagon®) to make sure they are fine.
