<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/NCT02238808</url>
  </required_header>
  <id_info>
    <org_study_id>EER001</org_study_id>
    <nct_id>NCT02238808</nct_id>
  </id_info>
  <brief_title>A Study to See Whether Estrogen Can Slow the Growth of Some ER Positive Breast Cancers</brief_title>
  <acronym>PRESTO</acronym>
  <official_title>PRe-operative ESTradiOl Window of Opportunity Study in Post-Menopausal Women With Newly Diagnosed ER Positive Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AHS Cancer Control Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AHS Cancer Control Alberta</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Some breast cancers have estrogen receptors (ER+). The investigators know that some ER+&#xD;
      tumours can be cured by hormone therapy alone while other ER+ breast cancers cannot.&#xD;
      Currently, there is no perfect way to tell these groups apart nor do the investigators know&#xD;
      why some respond when others do not.&#xD;
&#xD;
      Research findings suggest that the two types of ER+ breast cancers differ in their response&#xD;
      to estrogen with estrogen being toxic to one type and not the other. For those tumours that&#xD;
      find estrogen toxic, this may explain why tumours only start to grow when estrogen levels&#xD;
      decrease after menopause.&#xD;
&#xD;
      The purpose of this study is to see whether a two-week treatment of estrogen equal to&#xD;
      pre-menopausal estrogen levels will decrease the rate at which patients' ER+ tumours grow.&#xD;
      This will be done by comparing the growth rate in the tissue removed during standard of care&#xD;
      surgery after patients have been treated with 7-14 days of estrogen prior to that surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Breast cancer is a heterogeneous disease that includes two ER+ genetic subtypes (luminal A&#xD;
      and luminal B) that differ in their response to treatment.&#xD;
&#xD;
      Results from the Women's Health Initiative Trial showed that estrogen treated hysterectomized&#xD;
      women with no prior history of breast cancer had a significant and persistent decrease in&#xD;
      breast cancer incidence when compared to placebo treated participants. This implies that some&#xD;
      ER+ breast cancers are in fact growth inhibited by estrogens and are not growth promoted.&#xD;
&#xD;
      The hypothesis of this study is that some ER+ breast cancers (luminal A) are actually&#xD;
      sensitive (growth inhibited) by estrogen.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in&#xD;
           newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior&#xD;
           to surgery.&#xD;
&#xD;
        2. Exploratory analysis of biologic correlates with comparison to available genotyping&#xD;
           tests.&#xD;
&#xD;
      This is an open-label single group assignment pilot study for safety/efficacy and exploratory&#xD;
      biologic correlates&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>August 2015</start_date>
  <completion_date type="Anticipated">January 2027</completion_date>
  <primary_completion_date type="Actual">July 30, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior to surgery.</measure>
    <time_frame>end of 7-14 day treatment with estradiol</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exploratory analysis of biologic correlates with comparison to available genotyping tests</measure>
    <time_frame>end of 7-14 day treatment with estradiol</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of recurrence/survival data based on initial Ki67 response to 7-14 day trial of estradiol.</measure>
    <time_frame>10 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Estrogen Receptor Positive Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Estradiol treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Estradiol 6 mg daily for 7-14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Estradiol</intervention_name>
    <description>Eligible participants will take 2 mg Estradiol 3 times daily for 7-14 days pre-surgery.</description>
    <arm_group_label>Estradiol treatment</arm_group_label>
    <other_name>estrogen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female gender&#xD;
&#xD;
          -  Estrogen receptor positive (ER+) breast cancer&#xD;
&#xD;
          -  HER2 negative breast cancer&#xD;
&#xD;
          -  Post-menopausal by greater than 5 years&#xD;
&#xD;
          -  No previous hormonal replacement therapy&#xD;
&#xD;
          -  Low to intermediate histologic grade&#xD;
&#xD;
          -  ECOG Performance status of 0 of 1&#xD;
&#xD;
          -  Adequate hematological, renal and hepatic function is required&#xD;
&#xD;
          -  Ability to take oral medication&#xD;
&#xD;
          -  Patient must have adequate tissue for diagnosis, biomarkers and Ki67 assays&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-menopausal women&#xD;
&#xD;
          -  Locally advanced or metastatic breast cancer&#xD;
&#xD;
          -  Current, previous or planning for pre-operative treatment with chemotherapy, hormone&#xD;
             therapy including corticosteroids, radiation therapy for malignancy or other condition&#xD;
&#xD;
          -  Known hypersensitivity or intolerance to estradiol&#xD;
&#xD;
          -  Ischemic changes on baseline electrocardiogram&#xD;
&#xD;
          -  Symptomatic but untreated cholelithiasis&#xD;
&#xD;
          -  History of deep vein thrombosis, pulmonary embolism, stroke, acute myocardial&#xD;
             infarction, congestive cardiac failure, untreated hypertension or known inherited&#xD;
             hypercoagulable disorder&#xD;
&#xD;
          -  Undiagnosed abnormal vaginal bleeding or prior history of endometrial cancer&#xD;
&#xD;
          -  Untreated metabolic disturbances (glucose &gt; 15.0 mmol/L and triglycerides &gt; 400 mg/dL)&#xD;
&#xD;
          -  Current treatment with drugs known to be moderate or strong inhibitors of inducers of&#xD;
             isoenzyme CYP3A4&#xD;
&#xD;
          -  The time between study enrolment and definitive breast surgery is not sufficient for&#xD;
             administration of at least 7 days of estradiol&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Judith Hugh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alberta</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cross Cancer Institute</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>February 1, 2023</last_update_submitted>
  <last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ER+ breast cancer</keyword>
  <keyword>Luminal A</keyword>
  <keyword>Estradiol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Estrogens</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/NCT02238808
org study id: EER001
nct id: NCT02238808
lead sponsor: 
has dmc: No
Some breast cancers have estrogen receptors (ER+). The investigators know that some ER+
      tumours can be cured by hormone therapy alone while other ER+ breast cancers cannot.
      Currently, there is no perfect way to tell these groups apart nor do the investigators know
      why some respond when others do not.

      Research findings suggest that the two types of ER+ breast cancers differ in their response
      to estrogen with estrogen being toxic to one type and not the other. For those tumours that
      find estrogen toxic, this may explain why tumours only start to grow when estrogen levels
      decrease after menopause.

      The purpose of this study is to see whether a two-week treatment of estrogen equal to
      pre-menopausal estrogen levels will decrease the rate at which patients' ER+ tumours grow.
      This will be done by comparing the growth rate in the tissue removed during standard of care
      surgery after patients have been treated with 7-14 days of estrogen prior to that surgery.
Breast cancer is a heterogeneous disease that includes two ER+ genetic subtypes (luminal A
      and luminal B) that differ in their response to treatment.

      Results from the Women's Health Initiative Trial showed that estrogen treated hysterectomized
      women with no prior history of breast cancer had a significant and persistent decrease in
      breast cancer incidence when compared to placebo treated participants. This implies that some
      ER+ breast cancers are in fact growth inhibited by estrogens and are not growth promoted.

      The hypothesis of this study is that some ER+ breast cancers (luminal A) are actually
      sensitive (growth inhibited) by estrogen.

      Objectives:

        1. To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in
           newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior
           to surgery.

        2. Exploratory analysis of biologic correlates with comparison to available genotyping
           tests.

      This is an open-label single group assignment pilot study for safety/efficacy and exploratory
      biologic correlates
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To assess changes in breast cancer proliferation after a 7-14 day trial of estradiol in newly diagnosed estrogen receptor positive post-menopausal breast cancer patients prior to surgery.
time frame: end of 7-14 day treatment with estradiol
measure: Exploratory analysis of biologic correlates with comparison to available genotyping tests
time frame: end of 7-14 day treatment with estradiol
measure: Analysis of recurrence/survival data based on initial Ki67 response to 7-14 day trial of estradiol.
time frame: 10 years
arm group label: Estradiol treatment
arm group type: Experimental
description: Estradiol 6 mg daily for 7-14 days
intervention type: Drug
intervention name: Estradiol
description: Eligible participants will take 2 mg Estradiol 3 times daily for 7-14 days pre-surgery.
arm group label: Estradiol treatment
other name: estrogen
criteria: 
gender: Female
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
last name: Judith Hugh, MD
role: Principal Investigator
affiliation: University of Alberta
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Estradiol
mesh term: Estrogens
sharing ipd: No