Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial (TALES)

• ClinicalTrials.gov Identifier: NCT03011684
• Recruitment Status: Recruiting
• First Posted: January 5, 2017
• Last Update Posted: June 29, 2021
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Infertility	Drug: Tamoxifen; Drug: Letrozole	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial
• Actual Study Start Date: July 21, 2016
• Estimated Primary Completion Date: January 31, 2022
• Estimated Study Completion Date: January 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: ER Positive - Letrozole	Drug: Letrozole; For ER Positive Randomization
Experimental: ER Positive - Tamoxifen	Drug: Tamoxifen; For ER Positive Randomization
No Intervention: ER Negative

Outcome Measures

Primary Outcome Measures :

1. Mature Oocyte Yield [ Time Frame: Up to 2 weeks ]
   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. An Effect Size of 3 mature oocytes, based on clinically significant difference of 2 embryos to transfer. An average of 2 embryos are transferred per freeze-thaw cycle. If ~75% of mature oocytes will become embryos that can be frozen, then 3 mature oocytes should yield ~2 embryos for transfer. This effect size would effectively mean an additional event of embryos transferred.

Secondary Outcome Measures :

1. Compare change in estrogen levels during the ovarian stimulation cycle [ Time Frame: Up to 2 weeks ]
   Estrogen level data will be collected at baseline and after completion of the stimulation cycle
2. Compare change in progesterone levels during the ovarian stimulation cycle [ Time Frame: Up to 2 weeks ]
   Progesterone level data will be collected at baseline and after completion of the stimulation cycle
3. Compare change in androgen levels during the ovarian stimulation cycle [ Time Frame: Up to 2 weeks ]
   Androgen level data will be collected at baseline and after completion of the stimulation cycle
4. Compare change in estrogen in follicular fluid [ Time Frame: Up to 2 weeks ]
   Estrogen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
5. Compare change in letrozole in follicular fluid [ Time Frame: Up to 2 weeks ]
   Letrozole levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
6. Compare change in tamoxifen in follicular fluid [ Time Frame: Up to 2 weeks ]
   Tamoxifen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
7. Compare duration of stimulation (days) and total gonadotropin dose [ Time Frame: Up to 2 weeks ]
8. Number if competent oocytes on day 3 of embryo culture [ Time Frame: Up to 2 weeks ]
   To assess embryo quality, if applicable, on day 3 of embryo culture, a measure of the developmental competence of the oocytes.
9. Number if competent oocytes on day 5 of embryo culture [ Time Frame: Up to 2 weeks ]
   To assess embryo quality, if applicable, on day 5 of embryo culture, a measure of the developmental competence of the oocytes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Ange Wang, MD; 415-353-7475; Ange.Wang@ucsf.edu

Locations

United States, California

University of California at San Francisco; Recruiting

San Francisco, California, United States, 94143

Contact: Ange Wang, M.D. 415-353-7475 Ange.Wang@ucsf.edu

Principal Investigator: Mitchell Rosen, M.D.

Sponsors and Collaborators

University of California, San Francisco

Investigators

• Principal Investigator: Mitchell Rosen, MD; University of California, San Francisco

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT03011684
• Other Study ID Numbers: TALES Trial; NCI-2017-01809 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) ); 16751 ( Other Identifier: University of California, San Francisco )
• First Posted: January 5, 2017
• Last Update Posted: June 29, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of California, San Francisco:

Fertility Preservation; Breast Cancer

Additional relevant MeSH terms:

Infertility; Tamoxifen; Letrozole; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents