<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/NCT02236572</url>
  </required_header>
  <id_info>
    <org_study_id>1405013982</org_study_id>
    <nct_id>NCT02236572</nct_id>
  </id_info>
  <brief_title>Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score</brief_title>
  <official_title>A Neoadjuvant Phase II Trial of Aromatase Inhibitors in Combination With Everolimus in Postmenopausal Women With Hormone Receptor Positive/HER2 Negative Breast Cancers With Low and Intermediate Risk (&lt; 25) Oncotype Dx Recurrence Scores</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see whether adding everolimus to hormone treatment before&#xD;
      breast surgery will increase the chances of shrinking the breast cancer in those patients&#xD;
      with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or&#xD;
      less), compared to prior experience with hormone therapy alone. Everolimus is a drug&#xD;
      currently approved for use by the United States Food and Drug administration (FDA) for the&#xD;
      treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is&#xD;
      considered investigational for non-metastatic breast cancer patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single arm open-labeled neoadjuvant phase II clinical trial evaluating everolimus&#xD;
      in combination with an aromatase inhibitor in postmenopausal women with hormone receptor&#xD;
      positive/HER2 negative breast cancers with low and intermediate risk (&lt; 25) Recurrence Scores&#xD;
      by Oncotype Dx.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Phase 2 of recruitment was contingent on 5 of 15 patients responding, which did not occur.&#xD;
  </why_stopped>
  <start_date type="Actual">November 29, 2014</start_date>
  <completion_date type="Actual">March 1, 2021</completion_date>
  <primary_completion_date type="Actual">March 1, 2021</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>Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor</measure>
    <time_frame>up to 26 weeks</time_frame>
    <description>(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PEPI Score</measure>
    <time_frame>up to 26 weeks</time_frame>
    <description>To obtain the PEPI score, risk points for relapse-free survival (RFS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Ability to Tolerate Study Treatment With Minimal Side Effects</measure>
    <time_frame>Up to 26 weeks</time_frame>
    <description>Adverse events (using CTCAE (4.0)) that begin or worsen after informed consent were recorded. Adverse events are itemized in the adverse events module (in terms of total events and total participants experiencing events). Presented are the total number of participants that experience adverse events. For clarification, counts of participants that experienced serious adverse events and counts of participants that experienced 'other' (not serious) adverse events are presented separately.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Aromatase Inhibitor plus Everolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:&#xD;
Anastrozole 1 mg&#xD;
Letrozole 2.5 mg&#xD;
Exemestane 25 mg</description>
    <arm_group_label>Aromatase Inhibitor plus Everolimus</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have a histologically confirmed diagnosis of hormone receptor positive,&#xD;
             HER2 negative invasive breast carcinoma.&#xD;
&#xD;
          -  Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP&#xD;
             2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by&#xD;
             immunohistochemistry. Estrogen and/or progesterone receptor results by Oncotype Dx&#xD;
             will not be accepted.&#xD;
&#xD;
          -  Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by&#xD;
             IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and&#xD;
             must not be positive (must be a ratio of &lt; 2), but otherwise FISH/CISH is not required&#xD;
             if IHC is 0 or 1+ by institutional standards.&#xD;
&#xD;
          -  Patients must not have had prior ipsilateral breast-conserving surgery or total&#xD;
             mastectomy and be eligible for neoadjuvant treatment.&#xD;
&#xD;
          -  Clinical Stage II-IIIC (T2-4 N0-3 M0) by mammogram, ultrasound or MRI&#xD;
&#xD;
          -  Baseline Oncotpye Dx recurrence score &lt; 25.&#xD;
&#xD;
          -  Staging studies with a CT scan of the chest and abdomen and bone scan, or a PET/CT is&#xD;
             required for clinical stage III, and are considered optional for stage II breast&#xD;
             cancers.&#xD;
&#xD;
          -  Patients with multifocal, multicentric and synchronous bilateral breast cancers are&#xD;
             allowed:&#xD;
&#xD;
               -  Multifocal disease is defined as more than one invasive cancer &lt; 2 cm from the&#xD;
                  largest lesion within the same breast quadrant.&#xD;
&#xD;
               -  Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the&#xD;
                  largest lesion within the same breast quadrant or more than one lesion in&#xD;
                  different quadrants.&#xD;
&#xD;
               -  Synchronous bilateral disease is defined as invasive breast cancer in both&#xD;
                  breasts, diagnosed within 30 days of each other.&#xD;
&#xD;
               -  In patients with multicentric or bilateral invasive breast cancers, all sampled&#xD;
                  lesions must be hormone receptor-positive and HER2-negative. Any lesion measuring&#xD;
                  &gt; 1 cm must have an Oncotype Dx and the score must be &lt; 25. Lesions less than 1&#xD;
                  cm in size are not required to have an Oncotype Dx. One lesion (typically the&#xD;
                  largest) should be designated as the target lesion for which clinical and&#xD;
                  radiographic response to the neoadjuvant therapy will be judged.&#xD;
&#xD;
               -  Patients with a hormone receptor-positive, HER2-negative invasive cancer that&#xD;
                  meets study criteria may have ductal carcinoma in situ in another quadrant of the&#xD;
                  same breast or in the contralateral breast even if the DCIS is hormone&#xD;
                  receptor-negative.&#xD;
&#xD;
          -  Patients must have adequate bone marrow function, as defined by peripheral granulocyte&#xD;
             count of ≥ 1,500/mL, hemoglobin ≥ 9 g/dL and a platelet count ≥ 100,000/ mL within 28&#xD;
             days prior to registration.&#xD;
&#xD;
          -  Patients must have adequate hepatic function obtained within 28 days prior to&#xD;
             registration and documented by all of the following:&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 mg/dL (or ≤ 3.0 mg/dL if due to Gilbert's Syndrome)&#xD;
&#xD;
               -  ALT and AST ≤ 1.5 x Institutional Upper Limit of Normal (IULN)&#xD;
&#xD;
               -  Alkaline phosphatase ≤ 1.5 x IULN&#xD;
&#xD;
          -  Patients must have adequate renal function with serum creatinine level ≤ IULN within&#xD;
             28 days prior to registration.&#xD;
&#xD;
          -  Patients must have a fasting cholesterol ≤ 300 mg/dl OR ≤7.75 mmol/L and triglycerides&#xD;
             ≤ 2.5 x IULN obtained within 28 days prior to registration. Patients may be on lipid&#xD;
             lowering agents to reach these values.&#xD;
&#xD;
          -  Patients must have a ECOG performance status of 0-2.&#xD;
&#xD;
          -  Patients must be able to take oral medications.&#xD;
&#xD;
          -  Postmenopausal women (women are considered post-menopausal and not of child-bearing&#xD;
             potential if they are &gt; 18 years of age and have had 12 months of natural&#xD;
             (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate,&#xD;
             history of vasomotor symptoms or biochemically postmenopausal by estradiol and FSH&#xD;
             levels) prior to enrollment, or have had surgical bilateral oophorectomy (with or&#xD;
             without hysterectomy) prior to registration. Medical ovarian suppression with LHRH&#xD;
             agonists to render a patient postmenopausal will not be acceptable.&#xD;
&#xD;
             16. Patients or their legally authorized representative must be informed of the&#xD;
             investigational nature of this study and must sign and give written informed consent&#xD;
             prior to any screening procedures in accordance with institutional and federal&#xD;
             guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must not have inflammatory breast cancer (T4d) and must not have metastatic&#xD;
             breast cancer (Stage IV disease).&#xD;
&#xD;
          -  Patients must not have prior exposure to mTOR inhibitors (e.g. rapamycin, everolimus,&#xD;
             sirolimus, temsirolimus, deforolimus).&#xD;
&#xD;
          -  Patients must not have prior treatment with any investigational drug within the&#xD;
             preceding 28 days and must not be planning to receive any other investigational drug&#xD;
             for the duration of the study.&#xD;
&#xD;
          -  Patient may not have any impairment of gastrointestinal function or gastrointestinal&#xD;
             disease that may significantly alter the absorption of the drug (e.g. ulcerative&#xD;
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small&#xD;
             bowel resection).&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus as defined by HbA1c &gt;8% within 28 days prior to&#xD;
             registration despite adequate therapy.&#xD;
&#xD;
          -  Patients who have any severe and/or uncontrolled cardiac disease within ≤ 6 months&#xD;
             prior to start of everolimus, including: unstable angina pectoris, Symptomatic&#xD;
             congestive heart failure of New York heart Association Class III or IV, myocardial&#xD;
             infarction, serious uncontrolled cardiac arrhythmia, or any other clinically&#xD;
             significant cardiac disease&#xD;
&#xD;
          -  Patients must not have an organ allograft or other history of immune compromise.&#xD;
&#xD;
          -  Patients must not be receiving chronic, systemic treatment with corticosteroids or&#xD;
             other immunosuppressive agent. Topical or inhaled corticosteroids are allowed.&#xD;
&#xD;
          -  Patients must not have a known history of HIV seropositivity&#xD;
&#xD;
          -  Patients must not have a known diagnosis of hepatitis B or C. Patients with the&#xD;
             following risk factors must have hepatitis screening pre-treatment:&#xD;
&#xD;
               -  Blood transfusions prior to 1990&#xD;
&#xD;
               -  Current or prior IV drug users&#xD;
&#xD;
               -  Current or prior dialysis&#xD;
&#xD;
               -  Household contact with a hepatitis B or C patient&#xD;
&#xD;
               -  Current or prior high-risk sexual activity&#xD;
&#xD;
               -  History of jaundice.&#xD;
&#xD;
          -  Patients must not have any known uncontrolled underlying pulmonary disease or severely&#xD;
             impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation&#xD;
             88% or less at rest on room air),&#xD;
&#xD;
          -  Active (acute or chronic) or uncontrolled severe infection.&#xD;
&#xD;
          -  Patients who have received live attenuated vaccines within 1 week of start of&#xD;
             Everolimus, or have plans to receive such vaccination while on protocol treatment.&#xD;
             Patient should also avoid close contact with others who have received live attenuated&#xD;
             vaccines. Examples of live attenuated vaccines include intranasal influenza, measles,&#xD;
             mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines;&#xD;
&#xD;
          -  Patients who are currently part of or have participated in any clinical investigation&#xD;
             with an investigational drug within 1 month prior to dosing;&#xD;
&#xD;
          -  Patients must not have taken within 14 days prior to registration , be taking, nor&#xD;
             plan to take while on protocol treatment, strong CYP3A4 inhibitors, and/or CYP3A4&#xD;
             inducers.&#xD;
&#xD;
          -  Patients with active bleeding diathesis.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lajos Pusztai, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <results_first_submitted>October 22, 2021</results_first_submitted>
  <results_first_submitted_qc>January 12, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">February 1, 2022</results_first_posted>
  <last_update_submitted>January 12, 2022</last_update_submitted>
  <last_update_submitted_qc>January 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Postmenopausal</keyword>
  <keyword>ER-positive, PR-positive, HER2-negative</keyword>
  <keyword>Low and intermediate risk</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>Everolimus</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 16, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT02236572/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Aromatase Inhibitor Plus Everolimus</title>
          <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks&#xD;
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:&#xD;
Anastrozole 1 mg&#xD;
Letrozole 2.5 mg&#xD;
Exemestane 25 mg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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>Aromatase Inhibitor Plus Everolimus</title>
          <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks&#xD;
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:&#xD;
Anastrozole 1 mg&#xD;
Letrozole 2.5 mg&#xD;
Exemestane 25 mg</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="17"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66" lower_limit="54" upper_limit="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </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>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple or unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Clinical Tumor Size at Presentation - pt no.</title>
          <description>Clinical size was defined as the largest diameter on contrast-enhanced computed tomography. The higher the number (e.g. T1 compared to T3), the greater the progression.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>T1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>T2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>T3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Nodal Status at Presentation</title>
          <description>Nodal Status at Presentation: Lymph node status shows whether or not the lymph nodes in the underarm area (axillary lymph nodes) contain cancer:&#xD;
Lymph node-negative means none of the axillary lymph nodes contain cancer.&#xD;
Lymph node-positive means at least one axillary lymph node contains cancer.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Positive (biopsy proven)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tumor Histology</title>
          <description>A description of a tumor based on how abnormal the cancer cells and tissue look. Examples include; Ductal carcinoma in situ (DCIS), Lobular carcinoma in situ, Invasive ductal carcinoma (ductal breast cancer)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ductal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lobular</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor</title>
        <description>(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.</description>
        <time_frame>up to 26 weeks</time_frame>
        <population>15 patients had surgery.</population>
        <group_list>
          <group group_id="O1">
            <title>Aromatase Inhibitor Plus Everolimus</title>
            <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks&#xD;
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:&#xD;
Anastrozole 1 mg&#xD;
Letrozole 2.5 mg&#xD;
Exemestane 25 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor</title>
          <description>(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.</description>
          <population>15 patients had surgery.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>PEPI Score = 0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PEPI Score &gt; 0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PEPI Score</title>
        <description>To obtain the PEPI score, risk points for relapse-free survival (RFS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).</description>
        <time_frame>up to 26 weeks</time_frame>
        <population>Those that completed surgery</population>
        <group_list>
          <group group_id="O1">
            <title>Aromatase Inhibitor Plus Everolimus</title>
            <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks&#xD;
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:&#xD;
Anastrozole 1 mg&#xD;
Letrozole 2.5 mg&#xD;
Exemestane 25 mg</description>
          </group>
        </group_list>
        <measure>
          <title>PEPI Score</title>
          <description>To obtain the PEPI score, risk points for relapse-free survival (RFS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).</description>
          <population>Those that completed surgery</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="0" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participant Ability to Tolerate Study Treatment With Minimal Side Effects</title>
        <description>Adverse events (using CTCAE (4.0)) that begin or worsen after informed consent were recorded. Adverse events are itemized in the adverse events module (in terms of total events and total participants experiencing events). Presented are the total number of participants that experience adverse events. For clarification, counts of participants that experienced serious adverse events and counts of participants that experienced 'other' (not serious) adverse events are presented separately.</description>
        <time_frame>Up to 26 weeks</time_frame>
        <population>All participants that were enrolled in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Aromatase Inhibitor Plus Everolimus</title>
            <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks&#xD;
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:&#xD;
Anastrozole 1 mg&#xD;
Letrozole 2.5 mg&#xD;
Exemestane 25 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Participant Ability to Tolerate Study Treatment With Minimal Side Effects</title>
          <description>Adverse events (using CTCAE (4.0)) that begin or worsen after informed consent were recorded. Adverse events are itemized in the adverse events module (in terms of total events and total participants experiencing events). Presented are the total number of participants that experience adverse events. For clarification, counts of participants that experienced serious adverse events and counts of participants that experienced 'other' (not serious) adverse events are presented separately.</description>
          <population>All participants that were enrolled in the study.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with Serious Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with Other (Not Including Serious) Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 26 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Aromatase Inhibitor Plus Everolimus</title>
          <description>Aromatase inhibitor plus everolimus by mouth daily for 26 weeks&#xD;
Everolimus: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:&#xD;
Anastrozole 1 mg&#xD;
Letrozole 2.5 mg&#xD;
Exemestane 25 mg</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-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="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial Flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-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="17" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="9" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Lymph node pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Cardiac disorders - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vestibular disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="22" subjects_affected="12" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Oral dysesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="16" subjects_affected="10" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="8" subjects_affected="7" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatobiliary disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="7" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" events="11" subjects_affected="7" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Investigations - Other</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="20" subjects_affected="9" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </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="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="12" subjects_affected="7" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="10" subjects_affected="6" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="4" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Laryngeal inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="13" subjects_affected="10" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="26" subjects_affected="5" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Lajos Pusztai, MD, DPhil</name_or_title>
      <organization>Yale Cancer Center</organization>
      <phone>(203) 200-2328</phone>
      <email>lajos.pusztai@yale.edu</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/NCT02236572
org study id: 1405013982
nct id: NCT02236572
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to see whether adding everolimus to hormone treatment before
      breast surgery will increase the chances of shrinking the breast cancer in those patients
      with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or
      less), compared to prior experience with hormone therapy alone. Everolimus is a drug
      currently approved for use by the United States Food and Drug administration (FDA) for the
      treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is
      considered investigational for non-metastatic breast cancer patients.
This is a single arm open-labeled neoadjuvant phase II clinical trial evaluating everolimus
      in combination with an aromatase inhibitor in postmenopausal women with hormone receptor
      positive/HER2 negative breast cancers with low and intermediate risk (< 25) Recurrence Scores
      by Oncotype Dx.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor
time frame: up to 26 weeks
description: (PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.
measure: PEPI Score
time frame: up to 26 weeks
description: To obtain the PEPI score, risk points for relapse-free survival (RFS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).
measure: Participant Ability to Tolerate Study Treatment With Minimal Side Effects
time frame: Up to 26 weeks
description: Adverse events (using CTCAE (4.0)) that begin or worsen after informed consent were recorded. Adverse events are itemized in the adverse events module (in terms of total events and total participants experiencing events). Presented are the total number of participants that experience adverse events. For clarification, counts of participants that experienced serious adverse events and counts of participants that experienced 'other' (not serious) adverse events are presented separately.
arm group label: Aromatase Inhibitor plus Everolimus
arm group type: Experimental
description: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks
intervention type: Drug
intervention name: Everolimus
description: Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
Anastrozole 1 mg
Letrozole 2.5 mg
Exemestane 25 mg
arm group label: Aromatase Inhibitor plus Everolimus
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lajos Pusztai, MD
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Everolimus
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 