<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/NCT01669343</url>
  </required_header>
  <id_info>
    <org_study_id>AI Host Factors</org_study_id>
    <nct_id>NCT01669343</nct_id>
  </id_info>
  <brief_title>Aromatase Inhibitor Host Factors Study</brief_title>
  <official_title>Patient-related Predictors of Estrogen Suppression in Postmenopausal Women Using Adjuvant Letrozole</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine how key patient factors, including body size affect&#xD;
      how well letrozole suppresses circulating estrogen levels.&#xD;
&#xD;
      This study has two components: (1) Part A - an observational phase to evaluate the impact of&#xD;
      vitamin D and obesity on estrogen suppression in post-menopausal women already receiving&#xD;
      letrozole treatment, and (2) Part B - an interventional phase for women with body mass index&#xD;
      (BMI) &gt; 25 kg/m2 to assess the effect of double AI dose on estrogen levels.&#xD;
&#xD;
      If BMI or other patient factors reduce the effectiveness of letrozole, modifications to&#xD;
      treatment recommendations and studies to test higher dosing of letrozole may be needed to&#xD;
      maximize the benefit of this treatment and minimize the risk of the breast cancer coming&#xD;
      back.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The available evidence suggests that circulating estradiol levels play a critical role in&#xD;
      determining effectiveness of aromatase inhibitor therapy, and that maximal suppression of&#xD;
      aromatase activity and estrogen production is essential for optimal disease control. Host&#xD;
      factors such as high 25-Hydroxy Vitamin D (25-OH D) levels and obesity, which might increase&#xD;
      residual estrogen levels, could adversely impact outcome and lead to an increased risk of&#xD;
      recurrence or death. The primary objective of Part A (which includes women regardless of BMI)&#xD;
      is to directly evaluate the relationship between (i) 25-OH D levels and serum estrogen levels&#xD;
      and (ii) BMI and serum estrogen levels in a cohort of postmenopausal women on standard dose&#xD;
      letrozole therapy (2.5 mg/day). Part B (which includes only women with BMI &gt; 25 kg/m2) will&#xD;
      determine whether an increased dose of letrozole (5 mg/day), which had no dose limiting side&#xD;
      effects in a Phase I study improves suppression of estrogen in overweight/obese women.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <phase>N/A</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>Part A Correlation of Day 29 Estradiol With BMI</measure>
    <time_frame>Day 29</time_frame>
    <description>Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A Correlation of Day 29 Estrone With BMI</measure>
    <time_frame>Day 29</time_frame>
    <description>Determine if estrone levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed BMI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A Correlation of Day 29 Estradiol With Vitamin D</measure>
    <time_frame>Day 29</time_frame>
    <description>Determine if estradiol levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed Vitamin D level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A Correlation of Day 29 Estrone With Vitamin D</measure>
    <time_frame>Day 29</time_frame>
    <description>Determine if estrone levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed Vitamin D level</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B Change in Estradiol Level After Double Dose of Letrozole</measure>
    <time_frame>Day 29 to Day 58</time_frame>
    <description>In overweight/obese patients enrolled in part B, determine if blood levels of estradiol levels changed from before to after the double dose of letrozole</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma Letrozole</measure>
    <time_frame>Day 29 and day 58</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endocrine Symptoms During Part A of Study</measure>
    <time_frame>baseline, day 29 (end of part A)</time_frame>
    <description>Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endocrine Symptoms During Part B of the Study</measure>
    <time_frame>day 29 (end of part A) and day 58 (end of part B)</time_frame>
    <description>Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Musculoskeletal Symptoms</measure>
    <time_frame>baseline (day 1), day 29 (end of part A) and day 58 (end of part B)</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">121</enrollment>
  <condition>Breast Neoplasms</condition>
  <arm_group>
    <arm_group_label>Post-menopausal Women Using Adjuvant Letrozole</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.</description>
    <arm_group_label>Post-menopausal Women Using Adjuvant Letrozole</arm_group_label>
    <other_name>Femara</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenopausal female patients&#xD;
&#xD;
          -  histological confirmed diagnosis of estrogen receptor and/or progesterone receptor&#xD;
             positive breast cancer (Stage I-III) who have completed local therapy&#xD;
&#xD;
          -  Currently prescribed and taking letrozole 2.5 mg daily for a minimum of 3 months&#xD;
&#xD;
          -  Willing to provide written informed consent to participate&#xD;
&#xD;
          -  for the experimental arm: all of the above and body mass index (BMI) &gt; 25 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known abnormal liver or renal function defined by:&#xD;
&#xD;
               1. Serum Creatinine &gt; 1.25 times institutional upper limit of normal (ULN) or&#xD;
                  Calculated Creatinine Clearance &lt; 40 mL/min&#xD;
&#xD;
               2. Serum Bilirubin, Aspartate transaminase (AST) or alanine transaminase (ALT) &gt; 1.5&#xD;
                  times ULN&#xD;
&#xD;
          -  Presence of persistent local or known metastatic cancer&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Srikala Sridhar, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Margaret Hospital, Canada</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's College Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5S 1B1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2012</study_first_posted>
  <results_first_submitted>February 12, 2021</results_first_submitted>
  <results_first_submitted_qc>May 12, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 13, 2021</results_first_posted>
  <last_update_submitted>May 12, 2021</last_update_submitted>
  <last_update_submitted_qc>May 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aromatase Inhibitors</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>Letrozole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data supporting the related manuscript are kept in institutional file storage on an internal server at Lunenfeld-Tanenbaum Research Institute. There are de-identification concerns in small, regionally restricted, clinical datasets which prevent these data being openly available, but data will be made available at reasonable request from the corresponding author for up to and including 5 years from publication of the related manuscript.&#xD;
For all data requests please contact:&#xD;
Dr David Cescon, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Dave.Cescon@uhn.ca</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Up to and including 5 years from publication of the related manuscript (Elliott, Mitchell J et al. &quot;Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study.&quot; NPJ breast cancer vol. 6 22. 12 Jun. 2020)</ipd_time_frame>
    <ipd_access_criteria>Reasonable request</ipd_access_criteria>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Post-menopausal Women Using Adjuvant Letrozole</title>
          <description>Part A: All patients enrolled, on standard of care letrozole; Part B: All patients with BMI&gt;=25 who completed Part A, on a double dose of letrozole</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part A: All Patients</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="121"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="112"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligibility discovered after enrollment</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part B: Patients With BMI&gt;=25</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Recruited during interim analysis</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligibility discovered after enrollment</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Post-menopausal Women Using Adjuvant Letrozole</title>
          <description>Part A: All patients enrolled, on standard of care letrozole; Part B: All patients with BMI&gt;=25 who completed Part A, on a double dose of letrozole</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="112"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Only overweight/obese participant who completed Part A were enrolled in Part B</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Part A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.7" spread="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.0" spread="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Only overweight/obese participant who completed Part A were enrolled in Part B</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Part A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="112"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age at menopause</title>
          <population>Only overweight/obese participant who completed Part A were enrolled in Part B</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Part A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.2" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.4" spread="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Vitamin D supplementation</title>
          <population>Only overweight/obese participant who completed Part A were enrolled in Part B</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Part A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Letrozole use prior to study</title>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18.1" spread="17.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part A Correlation of Day 29 Estradiol With BMI</title>
        <description>Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI</description>
        <time_frame>Day 29</time_frame>
        <population>Part A</population>
        <group_list>
          <group group_id="O1">
            <title>Post-menopausal Women Using Adjuvant Letrozole</title>
            <description>Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants&#xD;
Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A Correlation of Day 29 Estradiol With BMI</title>
          <description>Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI</description>
          <population>Part A</population>
          <units>correlation coefficient</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" lower_limit="-0.13" upper_limit="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part A Correlation of Day 29 Estrone With BMI</title>
        <description>Determine if estrone levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed BMI</description>
        <time_frame>Day 29</time_frame>
        <population>Part A</population>
        <group_list>
          <group group_id="O1">
            <title>Post-menopausal Women Using Adjuvant Letrozole</title>
            <description>Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants&#xD;
Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A Correlation of Day 29 Estrone With BMI</title>
          <description>Determine if estrone levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed BMI</description>
          <population>Part A</population>
          <units>correlation coefficient</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07" lower_limit="-0.12" upper_limit="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part A Correlation of Day 29 Estradiol With Vitamin D</title>
        <description>Determine if estradiol levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed Vitamin D level</description>
        <time_frame>Day 29</time_frame>
        <population>Part A</population>
        <group_list>
          <group group_id="O1">
            <title>Post-menopausal Women Using Adjuvant Letrozole</title>
            <description>Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants&#xD;
Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A Correlation of Day 29 Estradiol With Vitamin D</title>
          <description>Determine if estradiol levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed Vitamin D level</description>
          <population>Part A</population>
          <units>correlation coefficient</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" lower_limit="-0.22" upper_limit="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part A Correlation of Day 29 Estrone With Vitamin D</title>
        <description>Determine if estrone levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed Vitamin D level</description>
        <time_frame>Day 29</time_frame>
        <population>Part A</population>
        <group_list>
          <group group_id="O1">
            <title>Post-menopausal Women Using Adjuvant Letrozole</title>
            <description>Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants&#xD;
Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A Correlation of Day 29 Estrone With Vitamin D</title>
          <description>Determine if estrone levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed Vitamin D level</description>
          <population>Part A</population>
          <units>correlation coefficient</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" lower_limit="-0.14" upper_limit="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B Change in Estradiol Level After Double Dose of Letrozole</title>
        <description>In overweight/obese patients enrolled in part B, determine if blood levels of estradiol levels changed from before to after the double dose of letrozole</description>
        <time_frame>Day 29 to Day 58</time_frame>
        <population>Part B participants</population>
        <group_list>
          <group group_id="O1">
            <title>Post-menopausal Women Using Adjuvant Letrozole</title>
            <description>Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants&#xD;
Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B Change in Estradiol Level After Double Dose of Letrozole</title>
          <description>In overweight/obese patients enrolled in part B, determine if blood levels of estradiol levels changed from before to after the double dose of letrozole</description>
          <population>Part B participants</population>
          <units>pmol/L</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" lower_limit="-0.56" upper_limit="0.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Letrozole</title>
        <time_frame>Day 29 and day 58</time_frame>
        <population>Data were not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Post-menopausal Women Using Adjuvant Letrozole</title>
            <description>Part B Double Dose Letrozole in overweight/obese participants&#xD;
Part B: In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Letrozole</title>
          <population>Data were not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Endocrine Symptoms During Part A of Study</title>
        <description>Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life</description>
        <time_frame>baseline, day 29 (end of part A)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Post-menopausal Women Using Adjuvant Letrozole</title>
            <description>Part A: All patients enrolled, on standard of care letrozole</description>
          </group>
        </group_list>
        <measure>
          <title>Endocrine Symptoms During Part A of Study</title>
          <description>Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.4" spread="9.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.9" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Musculoskeletal Symptoms</title>
        <time_frame>baseline (day 1), day 29 (end of part A) and day 58 (end of part B)</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Endocrine Symptoms During Part B of the Study</title>
        <description>Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life</description>
        <time_frame>day 29 (end of part A) and day 58 (end of part B)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Part B</title>
            <description>Part B: Patients With BMI&gt;=25, on double dose of letrozole</description>
          </group>
        </group_list>
        <measure>
          <title>Endocrine Symptoms During Part B of the Study</title>
          <description>Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.7" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 58</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.2" spread="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected over the duration of the study: 29 days for patients taking part in Part A only, 58 days for patients that took part in Parts A and B</time_frame>
      <desc>National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.01</desc>
      <group_list>
        <group group_id="E1">
          <title>Full Study</title>
          <description>Adverse events collected during part A, 29 days of monitored adherence to standard of care letrozole and Part B .</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE Version 4.01</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal Colic/Constipation</sub_title>
                <description>Hospitalized for grade 3 Renal Colic/Constipation</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Stroke</sub_title>
                <description>Hospitalized for stroke, grade 2</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE Version 4.01</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. David Cescon</name_or_title>
      <organization>Princess Margaret Hospital</organization>
      <phone>416-946-2000</phone>
      <email>dave.cescon@uhn.on.ca</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01669343
org study id: AI Host Factors
nct id: NCT01669343
lead sponsor: 
has dmc: No
The purpose of this study is to examine how key patient factors, including body size affect
      how well letrozole suppresses circulating estrogen levels.

      This study has two components: (1) Part A - an observational phase to evaluate the impact of
      vitamin D and obesity on estrogen suppression in post-menopausal women already receiving
      letrozole treatment, and (2) Part B - an interventional phase for women with body mass index
      (BMI) > 25 kg/m2 to assess the effect of double AI dose on estrogen levels.

      If BMI or other patient factors reduce the effectiveness of letrozole, modifications to
      treatment recommendations and studies to test higher dosing of letrozole may be needed to
      maximize the benefit of this treatment and minimize the risk of the breast cancer coming
      back.
The available evidence suggests that circulating estradiol levels play a critical role in
      determining effectiveness of aromatase inhibitor therapy, and that maximal suppression of
      aromatase activity and estrogen production is essential for optimal disease control. Host
      factors such as high 25-Hydroxy Vitamin D (25-OH D) levels and obesity, which might increase
      residual estrogen levels, could adversely impact outcome and lead to an increased risk of
      recurrence or death. The primary objective of Part A (which includes women regardless of BMI)
      is to directly evaluate the relationship between (i) 25-OH D levels and serum estrogen levels
      and (ii) BMI and serum estrogen levels in a cohort of postmenopausal women on standard dose
      letrozole therapy (2.5 mg/day). Part B (which includes only women with BMI > 25 kg/m2) will
      determine whether an increased dose of letrozole (5 mg/day), which had no dose limiting side
      effects in a Phase I study improves suppression of estrogen in overweight/obese women.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part A Correlation of Day 29 Estradiol With BMI
time frame: Day 29
description: Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI
measure: Part A Correlation of Day 29 Estrone With BMI
time frame: Day 29
description: Determine if estrone levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed BMI
measure: Part A Correlation of Day 29 Estradiol With Vitamin D
time frame: Day 29
description: Determine if estradiol levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed Vitamin D level
measure: Part A Correlation of Day 29 Estrone With Vitamin D
time frame: Day 29
description: Determine if estrone levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed Vitamin D level
measure: Part B Change in Estradiol Level After Double Dose of Letrozole
time frame: Day 29 to Day 58
description: In overweight/obese patients enrolled in part B, determine if blood levels of estradiol levels changed from before to after the double dose of letrozole
measure: Plasma Letrozole
time frame: Day 29 and day 58
measure: Endocrine Symptoms During Part A of Study
time frame: baseline, day 29 (end of part A)
description: Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life
measure: Endocrine Symptoms During Part B of the Study
time frame: day 29 (end of part A) and day 58 (end of part B)
description: Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life
measure: Musculoskeletal Symptoms
time frame: baseline (day 1), day 29 (end of part A) and day 58 (end of part B)
arm group label: Post-menopausal Women Using Adjuvant Letrozole
arm group type: Other
description: Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants
intervention type: Drug
intervention name: Letrozole
description: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.
arm group label: Post-menopausal Women Using Adjuvant Letrozole
other name: Femara
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Srikala Sridhar, M.D.
role: Principal Investigator
affiliation: Princess Margaret Hospital, Canada
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Letrozole
sharing ipd: Yes
ipd description: The data supporting the related manuscript are kept in institutional file storage on an internal server at Lunenfeld-Tanenbaum Research Institute. There are de-identification concerns in small, regionally restricted, clinical datasets which prevent these data being openly available, but data will be made available at reasonable request from the corresponding author for up to and including 5 years from publication of the related manuscript.
For all data requests please contact:
Dr David Cescon, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Dave.Cescon@uhn.ca
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Up to and including 5 years from publication of the related manuscript (Elliott, Mitchell J et al. "Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study." NPJ breast cancer vol. 6 22. 12 Jun. 2020)
ipd access criteria: Reasonable request
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 