<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03011684</url>
  </required_header>
  <id_info>
    <org_study_id>TALES Trial</org_study_id>
    <secondary_id>NCI-2017-01809</secondary_id>
    <secondary_id>16751</secondary_id>
    <nct_id>NCT03011684</nct_id>
  </id_info>
  <brief_title>Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial</brief_title>
  <acronym>TALES</acronym>
  <official_title>Fertility Preservation Using Tamoxifen and Letrozole in Estrogen Sensitive Tumors Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Latrogenic infertility as a result of cancer treatment has a profound effect on long-term&#xD;
      quality of life in survivors of reproductive-age cancers. Oocyte cryopreservation prior to&#xD;
      cancer treatment has been associated with improved quality of life, with a potential ability&#xD;
      to reduce long-term decision-related regret in cancer survivors. Though letrozole plus&#xD;
      gonadotropin and and tamoxifen plus gonadotropin are currently routinely used worldwide in&#xD;
      ovarian stimulation cycles for fertility preservation in patients with&#xD;
      estrogen-receptor-positive breast cancer, it is not clear which of the two might lead to&#xD;
      improved oocyte yield. Improved knowledge about the efficacy of these medications, with&#xD;
      regard to oocyte yield, has the potential to significantly improve quality of life in&#xD;
      reproductive-age breast cancer survivors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose:&#xD;
&#xD;
      Our primary objective is to determine whether concomitant administration of tamoxifen 20 mg&#xD;
      oral with gonadotropins (tamoxifen-gonadotropin) versus a starting dose of letrozole 5 mg&#xD;
      oral with gonadotropins (letrozole-gonadotropin) will result in a difference in mature oocyte&#xD;
      yield during our routine ovarian stimulation protocol for fertility preservation for&#xD;
      Estrogen-Receptor-Positive (ER+) breast cancer.&#xD;
&#xD;
      Specific Aims: Each of the following aims will include a primary comparison and secondary&#xD;
      comparisons.&#xD;
&#xD;
      Primary aim: The primary aim will be to compare patients with ER+ breast cancer who are&#xD;
      treated with letrozole-gonadotropin versus patients with ER+ breast cancer who are treated&#xD;
      tamoxifen-gonadotropin with regard to ovarian stimulation outcomes.&#xD;
&#xD;
        -  Primary comparison:&#xD;
&#xD;
           1) To determine if the assigned stimulation regimen will result in a difference in&#xD;
           mature (meiosis II) oocyte yield in patients with breast cancer who undergo ovarian&#xD;
           stimulation for fertility preservation.&#xD;
&#xD;
        -  Secondary comparison:&#xD;
&#xD;
             1. To compare estrogen, progesterone, and androgen levels during the ovarian&#xD;
                stimulation cycle.&#xD;
&#xD;
             2. To compare estrogen, letrozole, and tamoxifen levels in follicular fluid.&#xD;
&#xD;
             3. To compare duration of stimulation (days) and total gonadotropin dose&#xD;
                (international units of FSH).&#xD;
&#xD;
             4. To assess embryo quality, if applicable, on day 3 and day 5 of embryo culture, a&#xD;
                measure of the developmental competence of the oocytes.&#xD;
&#xD;
        -  Experimental comparison:&#xD;
&#xD;
             1. To compare clinical pregnancy rates when cryopreserved tissue is eventually&#xD;
                utilized among patients from the assigned stimulation regimens. This comparison is&#xD;
                labeled experimental because of the remoteness of such an outcome from our present&#xD;
                study.&#xD;
&#xD;
      Secondary Aim: We will repeat the above comparisons among patients with ER+ breast cancer who&#xD;
      are treated with tamoxifen-gonadotropin versus a prospectively-obtained reference group of&#xD;
      patients with Estrogen-Receptor-Negative (ER-) breast cancer who are treated gonadotropin&#xD;
      alone. We will then again repeat the above comparisons among patients with ER+ breast cancer&#xD;
      who are treated letrozole-gonadotropin versus patients with ER- breast cancer who are treated&#xD;
      gonadotropin alone.&#xD;
&#xD;
      Experimental Design and Methods:&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      The target population is reproductive-age women who have been recently diagnosed with ER+&#xD;
      breast cancer and choose to undergo oocyte or embryo cryopreservation prior to chemotherapy&#xD;
      treatment. All eligible women will be asked to join the study at their initial University of&#xD;
      California, San Francisco (UCSF) fertility preservation consult. Study participants will be&#xD;
      recruited from the Reproductive Endocrinology Clinic at University of California, San&#xD;
      Francisco Center for Reproductive Health. A consecutive sample with ER- disease will also be&#xD;
      recruited at the same type of visit. They will be asked to take part in the gonadotropin only&#xD;
      stimulation group, which will be used for a secondary aim.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 21, 2016</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mature Oocyte Yield</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare change in estrogen levels during the ovarian stimulation cycle</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Estrogen level data will be collected at baseline and after completion of the stimulation cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare change in progesterone levels during the ovarian stimulation cycle</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Progesterone level data will be collected at baseline and after completion of the stimulation cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare change in androgen levels during the ovarian stimulation cycle</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Androgen level data will be collected at baseline and after completion of the stimulation cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare change in estrogen in follicular fluid</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Estrogen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare change in letrozole in follicular fluid</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Letrozole levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare change in tamoxifen in follicular fluid</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Tamoxifen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare duration of stimulation (days) and total gonadotropin dose</measure>
    <time_frame>Up to 2 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number if competent oocytes on day 3 of embryo culture</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>To assess embryo quality, if applicable, on day 3 of embryo culture, a measure of the developmental competence of the oocytes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number if competent oocytes on day 5 of embryo culture</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>To assess embryo quality, if applicable, on day 5 of embryo culture, a measure of the developmental competence of the oocytes.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">144</enrollment>
  <condition>Infertility</condition>
  <arm_group>
    <arm_group_label>ER Positive - Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ER Positive - Tamoxifen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ER Negative</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen</intervention_name>
    <description>For ER Positive Randomization</description>
    <arm_group_label>ER Positive - Tamoxifen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>For ER Positive Randomization</description>
    <arm_group_label>ER Positive - Letrozole</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  New breast cancer diagnosis&#xD;
&#xD;
          -  Has not yet begun chemotherapy&#xD;
&#xD;
          -  Desires to undergo ovarian stimulation and oocyte retrieval prior to cancer treatment&#xD;
&#xD;
          -  Age 18 years old or greater&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chemotherapy has already commenced or been completed&#xD;
&#xD;
          -  History of recurrent breast cancer (with a prior history of chemotherapy)&#xD;
&#xD;
          -  Stage IV breast cancer diagnosis (metastases remote from the breast)&#xD;
&#xD;
          -  Patient's oncologist advises against the trial - in which case they can choose to&#xD;
             receive stimulation with letrozole+gonadotropin&#xD;
&#xD;
          -  Does not plan to undergo ovarian stimulation and oocyte retrieval prior to diagnosis&#xD;
&#xD;
          -  Any significant concurrent disease, illness, or psychiatric disorder that would&#xD;
             compromise patient safety or compliance, interfere with consent, study participation,&#xD;
             follow-up, or interpretation of study results&#xD;
&#xD;
          -  Age less than 18 years old&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mitchell Rosen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ange Wang, MD</last_name>
    <phone>415-353-7475</phone>
    <email>Ange.Wang@ucsf.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California at San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ange Wang, M.D.</last_name>
      <phone>415-353-7475</phone>
      <email>Ange.Wang@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Mitchell Rosen, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fertility Preservation</keyword>
  <keyword>Breast Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tamoxifen</mesh_term>
    <mesh_term>Letrozole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03011684
org study id: TALES Trial
secondary id: NCI-2017-01809
secondary id: 16751
nct id: NCT03011684
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mature Oocyte Yield
time frame: Up to 2 weeks
description: 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.
measure: Compare change in estrogen levels during the ovarian stimulation cycle
time frame: Up to 2 weeks
description: Estrogen level data will be collected at baseline and after completion of the stimulation cycle
measure: Compare change in progesterone levels during the ovarian stimulation cycle
time frame: Up to 2 weeks
description: Progesterone level data will be collected at baseline and after completion of the stimulation cycle
measure: Compare change in androgen levels during the ovarian stimulation cycle
time frame: Up to 2 weeks
description: Androgen level data will be collected at baseline and after completion of the stimulation cycle
measure: Compare change in estrogen in follicular fluid
time frame: Up to 2 weeks
description: Estrogen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
measure: Compare change in letrozole in follicular fluid
time frame: Up to 2 weeks
description: Letrozole levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
measure: Compare change in tamoxifen in follicular fluid
time frame: Up to 2 weeks
description: Tamoxifen levels in follicular fluid will be collected at baseline and after completion of the stimulation cycle
measure: Compare duration of stimulation (days) and total gonadotropin dose
time frame: Up to 2 weeks
measure: Number if competent oocytes on day 3 of embryo culture
time frame: Up to 2 weeks
description: To assess embryo quality, if applicable, on day 3 of embryo culture, a measure of the developmental competence of the oocytes.
measure: Number if competent oocytes on day 5 of embryo culture
time frame: Up to 2 weeks
description: To assess embryo quality, if applicable, on day 5 of embryo culture, a measure of the developmental competence of the oocytes.
arm group label: ER Positive - Letrozole
arm group type: Experimental
arm group label: ER Positive - Tamoxifen
arm group type: Experimental
arm group label: ER Negative
arm group type: No Intervention
intervention type: Drug
intervention name: Tamoxifen
description: For ER Positive Randomization
arm group label: ER Positive - Tamoxifen
intervention type: Drug
intervention name: Letrozole
description: For ER Positive Randomization
arm group label: ER Positive - Letrozole
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Mitchell Rosen, MD
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Ange Wang, MD
phone: 415-353-7475
email: Ange.Wang@ucsf.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Infertility
mesh term: Tamoxifen
mesh term: Letrozole
sharing ipd: No