Clinical trial NCT03011684: Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial
Official title: Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Infertility
Keywords: Fertility Preservation
Breast Cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2017-01-05
Enrollment: 309
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized at the time of enrollment to 1 of 2 experimental arms.
Primary purpose: TREATMENT

Brief summary: Latrogenic infertility as a result of cancer treatment has a profound effect on long-term quality of life in survivors of reproductive-age cancers. Oocyte cryopreservation prior to cancer treatment has been associated with improved quality of life, with a potential ability to reduce long-term decision-related regret in cancer survivors. Though letrozole plus gonadotropin and and tamoxifen plus gonadotropin are currently routinely used worldwide in ovarian stimulation cycles for fertility preservation in patients with estrogen-receptor-positive breast cancer, it is not clear which of the two might lead to improved oocyte yield. Improved knowledge about the efficacy of these medications, with regard to oocyte yield, has the potential to significantly improve quality of life in reproductive-age breast cancer survivors.

Detailed description: Purpose:

Our primary objective is to determine whether concomitant administration of tamoxifen 20 mg oral with gonadotropins (tamoxifen-gonadotropin) versus a starting dose of letrozole 5 mg oral with gonadotropins (letrozole-gonadotropin) will result in a difference in mature oocyte yield during our routine ovarian stimulation protocol for fertility preservation for Estrogen-Receptor-Positive (ER+) breast cancer.

Specific Aims: Each of the following aims will include a primary comparison and secondary comparisons.

Primary aim: The primary aim will be to compare patients with ER+ breast cancer who are treated with letrozole-gonadotropin versus patients with ER+ breast cancer who are treated tamoxifen-gonadotropin with regard to ovarian stimulation outcomes.

* Primary comparison:

  1) To determine if the assigned stimulation regimen will result in a difference in mature (meiosis II) oocyte yield in patients with breast cancer who undergo ovarian stimulation for fertility preservation.
* Secondary comparison:

  1. To compare estrogen, progesterone, and androgen levels during the ovarian stimulation cycle.
  2. To compare estrogen, letrozole, and tamoxifen levels in follicular fluid.
  3. To compare duration of stimulation (days) and total gonadotropin dose (international units of FSH).
  4. To assess embryo quality, if applicable, on day 3 and day 5 of embryo culture, a measure of the developmental competence of the oocytes.
* Experimental comparison:

  1. To compare clinical pregnancy rates when cryopreserved tissue is eventually utilized among patients from the assigned stimulation regimens. This comparison is labeled experimental because of the remoteness of such an outcome from our present study.

Secondary Aim: We will repeat the above comparisons among patients with ER+ breast cancer who are treated with tamoxifen-gonadotropin versus a prospectively-obtained reference group of patients with Estrogen-Receptor-Negative (ER-) breast cancer who are treated gonadotropin alone. We will then again repeat the above comparisons among patients with ER+ breast cancer who are treated letrozole-gonadotropin versus patients with ER- breast cancer who are treated gonadotropin alone.

Experimental Design and Methods:

Study population:

The target population is reproductive-age women who have been recently diagnosed with ER+ breast cancer and choose to undergo oocyte or embryo cryopreservation prior to chemotherapy treatment. All eligible women will be asked to join the study at their initial University of California, San Francisco (UCSF) fertility preservation consult. Study participants will be recruited from the Reproductive Endocrinology Clinic at University of California, San Francisco Center for Reproductive Health. A consecutive sample with ER- disease will also be recruited at the same type of visit. They will be asked to take part in the gonadotropin only stimulation group, which will be used for a secondary aim.

Eligibility criteria: Inclusion Criteria:

* New breast cancer diagnosis
* Has not yet begun chemotherapy
* Desires to undergo ovarian stimulation and oocyte retrieval prior to cancer treatment
* Age 18 years old or greater

Exclusion Criteria:

* Chemotherapy has already commenced or been completed
* History of recurrent breast cancer (with a prior history of chemotherapy)
* Stage IV breast cancer diagnosis (metastases remote from the breast)
* Patient's oncologist advises against the trial - in which case they can choose to receive stimulation with letrozole+gonadotropin
* Does not plan to undergo ovarian stimulation and oocyte retrieval prior to diagnosis
* Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results
* Age less than 18 years old

Primary outcomes:
measure: Mature Oocyte Yield
timeFrame: Up to 2 weeks
Secondary outcomes:
measure: Compare change in estrogen levels during the ovarian stimulation cycle
timeFrame: Up to 2 weeks
measure: Compare change in progesterone levels during the ovarian stimulation cycle
timeFrame: Up to 2 weeks
measure: Compare change in androgen levels during the ovarian stimulation cycle
timeFrame: Up to 2 weeks
measure: Compare change in estrogen in follicular fluid
timeFrame: Up to 2 weeks
measure: Compare change in letrozole in follicular fluid
timeFrame: Up to 2 weeks
measure: Compare change in tamoxifen in follicular fluid
timeFrame: Up to 2 weeks
measure: Compare duration of stimulation (days) and total gonadotropin dose
timeFrame: Up to 2 weeks
measure: Number if competent oocytes on day 3 of embryo culture
timeFrame: Up to 2 weeks
measure: Number if competent oocytes on day 5 of embryo culture
timeFrame: Up to 2 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Mitchell Rosen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Letourneau J, Juarez-Hernandez F, Wald K, Ribeiro S, Wang A, McCulloch CE, Mok-Lin E, Dolezal M, Chien AJ, Cedars MI, Rosen M. Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial. J Assist Reprod Genet. 2021 Sep;38(9):2455-2463. doi: 10.1007/s10815-021-02273-3. Epub 2021 Jul 26.