<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/NCT03300557</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-01782</org_study_id>
    <secondary_id>NCI-2017-01782</secondary_id>
    <secondary_id>UW17010</secondary_id>
    <secondary_id>N01-CN-2012-00033</secondary_id>
    <secondary_id>2016LS183 / UWI17010/UAB1788</secondary_id>
    <secondary_id>UWI2016-08-01</secondary_id>
    <secondary_id>N01CN00033</secondary_id>
    <secondary_id>P30CA014520</secondary_id>
    <nct_id>NCT03300557</nct_id>
  </id_info>
  <brief_title>Exemestane in Treating Patients With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer</brief_title>
  <official_title>Pilot Study of Daily Exemestane in Women With Complex Atypical Hyperplasia of the Endometrium/Endometrial Intraepithelial Neoplasia or Low Grade Endometrial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot phase IIa trial studies how well exemestane works in treating patients with&#xD;
      complex atypical hyperplasia of the endometrium/endometrial intraepithelial neoplasia or low&#xD;
      grade endometrial cancer. Exemestane may stop the growth of tumor cells by blocking some of&#xD;
      the enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine if there is a decrease in proliferation index, measured by Ki-67 expression,&#xD;
      in complex atypical hyperplasia (CAH)/endometrial intraepithelial neoplasia (EIN) or low&#xD;
      grade (grade 1 and grade 2) endometrial cancer cells from baseline to post-exemestane&#xD;
      treatment.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Circulating serum estradiol and progesterone. II. Pathological response (regression of&#xD;
      CAH/EIN or low grade [grade 1 and grade 2] endometrial carcinoma).&#xD;
&#xD;
      III. Tissue biomarkers. IV. Deoxyribonucleic acid (DNA) mutational analysis through next&#xD;
      generation sequencing and methylation status of endometrial tumor.&#xD;
&#xD;
      V. Protein markers via tampon recovery before and after treatment. VI. DNA markers via tampon&#xD;
      recovery. VII. Safety and adverse effects of treatment. VIII. Comparison of Ki-67 expression&#xD;
      changes between study subjects and a historical cohort.&#xD;
&#xD;
      IX. Evaluation of the levels of exemestane in the plasma samples pre and post treatment.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive exemestane orally (PO) once daily (QD) over 21-42 days in the absence of&#xD;
      disease progression or unaccepted toxicity. Patients undergo standard of care surgery between&#xD;
      days 22-43.&#xD;
&#xD;
      After completion of study treatment, patients with unresolved adverse events on day of&#xD;
      surgery are followed up periodically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 15, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in tumor proliferation</measure>
    <time_frame>Baseline up to 7 months</time_frame>
    <description>Will be measured by change in Ki-67 expression. Will evaluate the change from baseline to post-exposure in absolute change in percent Ki-67 using one-sample Student's t-test or Wilcoxon signed-rank test, as appropriate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in circulating serum estradiol</measure>
    <time_frame>Baseline up to 7 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in circulating serum progesterone</measure>
    <time_frame>Baseline up to 7 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathological response to exemestane</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Will assess regression of complex atypical hyperplasia/endometrial intraepithelial neoplasia and low grade (grade 1 and grade 2) endometrial carcinoma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tissue marker analysis</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Will assess apoptosis (cleaved caspase 3), proliferation (cyclin D1), insulin pathway (pAKT, IGF-1R), and endocrine regulation (estrogen receptor/progesterone receptor/androgen receptor).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Deoxyribonucleic acid (DNA) mutational analysis</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Will be analyzed by next generation sequencing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Methylation status of endometrial tumor</measure>
    <time_frame>Up to 7 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein and DNA markers</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Will be assessed via tampon recovery pre and post exemestane treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ki-67 expression</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Will compare Ki-67 expression between participants samples and historically matched samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma levels of exemestane</measure>
    <time_frame>Up to 7 months</time_frame>
    <description>Will evaluate plasma levels of exemestane pre and post treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Atypical Hyperplasia</condition>
  <condition>Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia</condition>
  <condition>FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma</condition>
  <condition>FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (exemestane)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exemestane</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (exemestane)</arm_group_label>
    <other_name>Aromasin</other_name>
    <other_name>FCE-24304</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (exemestane)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacokinetic Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (exemestane)</arm_group_label>
    <other_name>PHARMACOKINETIC</other_name>
    <other_name>PK Study</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (exemestane)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females with a histologically proven CAH/ EIN or low grade (grade 1 or grade 2)&#xD;
             endometrial carcinoma (EC) for which surgery is planned; the pathologic report from&#xD;
             the referring facility will be used to determine pathologic eligibility; this report&#xD;
             must be within 45 days of their baseline (pre-surgical) clinic visit&#xD;
&#xD;
          -  No prior treatment for CAH/EIN/EC&#xD;
&#xD;
          -  Post-menopausal confirmed with one the following criteria:&#xD;
&#xD;
               -  &gt;= 60 years of age&#xD;
&#xD;
               -  Age 56 to 59 years of age with &gt;= 2 years of amenorrhea&#xD;
&#xD;
               -  Age 56 to 59 years of age with &lt; 2 years of amenorrhea and follicle stimulating&#xD;
                  hormone (FSH) within institutional post-menopausal range.&#xD;
&#xD;
               -  Age 45 to 55 years of age with FSH within institutional post-menopausal range.&#xD;
                  The Ki-67 expression changes based on menopausal status and specifically varies&#xD;
                  based on what phase of the menstrual cycle the sample is collected. Therefore, in&#xD;
                  order to eliminate this source of variability, only postmenopausal women will be&#xD;
                  included in this trial. In addition, exemestane is currently approved for use in&#xD;
                  post-menopausal women only.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 1&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x upper limit of normal or calculated creatinine clearance &gt;=&#xD;
             60 mL/min using Cockcroft-Gault equation for patients with creatinine levels &gt; 1.5 x&#xD;
             institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x ULN OR direct bilirubin =&lt; 1 x ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =&lt; 2.5 x ULN&#xD;
&#xD;
          -  White blood cell (WBC) &gt;= 3000/mcl&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcl&#xD;
&#xD;
          -  Able and willing to take oral medications&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Body mass index (BMI) &gt; 20&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who had curatively treated invasive malignancies for which all treatments&#xD;
             ended within 1 year prior to the study (with the exception of basal cell or squamous&#xD;
             cell carcinoma of the skin)&#xD;
&#xD;
          -  Not a surgical candidate or surgery is not scheduled within 43 days from starting the&#xD;
             study drug&#xD;
&#xD;
          -  Receiving any other investigational agents&#xD;
&#xD;
          -  Any gastrointestinal condition causing malabsorption or obstruction (e.g. celiac&#xD;
             sprue, gastric bypass surgery, strictures, adhesions, history of small bowel&#xD;
             resection, blind loop syndrome)&#xD;
&#xD;
          -  Has been on any hormonal treatment (including progestin-containing intrauterine device&#xD;
             [IUD]) for CAH/EIN or low grade (grade 1 or grade 2) endometrial carcinoma in last 3&#xD;
             months&#xD;
&#xD;
          -  Use hormone replacement therapy (including systemic or topical estrogen, progesterone,&#xD;
             or testosterone based medication) or/and phytoestrogen supplements (i.e. black cohosh)&#xD;
             or has been on progestin (including progestin containing IUD), tamoxifen or aromatase&#xD;
             inhibitor within the prior 3 months&#xD;
&#xD;
          -  Concomitant use of strong CYP3A4 inducers such as rifampicin, phenytoin,&#xD;
             carbamazepine, phenobarbital or St. John's wort as these may significantly reduce the&#xD;
             availability of exemestane&#xD;
&#xD;
          -  Known hypersensitivity to exemestane or its excipients&#xD;
&#xD;
          -  Known intercurrent illness or psychiatric illness/social situations that will limit&#xD;
             compliance with study requirements&#xD;
&#xD;
          -  Evidence or high suspicion of metastatic disease at enrollment&#xD;
&#xD;
          -  Women with severe bone density issues/osteoporosis (defined as any medical treatment&#xD;
             for osteoporosis, and/or a T-score of -2.5 or lower, and/or history of fracture of the&#xD;
             hip or spine)&#xD;
&#xD;
          -  Unwilling or unable to undergo research biopsy during the baseline (pre-surgical)&#xD;
             clinic visit, or inadequate research biopsy obtained during the baseline&#xD;
             (pre-surgical) clinic visit (determined by the gynecologic oncologist at the time of&#xD;
             the subject's pelvic exam)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Britt K Erickson</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota/Masonic Cancer Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Italy</country>
  </removed_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>April 15, 2023</last_update_submitted>
  <last_update_submitted_qc>April 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Carcinoma in Situ</mesh_term>
    <mesh_term>Carcinoma, Endometrioid</mesh_term>
    <mesh_term>Endometrial Hyperplasia</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exemestane</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>November 8, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03300557/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03300557
org study id: NCI-2017-01782
secondary id: NCI-2017-01782
secondary id: UW17010
secondary id: N01-CN-2012-00033
secondary id: 2016LS183 / UWI17010/UAB1788
secondary id: UWI2016-08-01
secondary id: N01CN00033
secondary id: P30CA014520
nct id: NCT03300557
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This pilot phase IIa trial studies how well exemestane works in treating patients with
      complex atypical hyperplasia of the endometrium/endometrial intraepithelial neoplasia or low
      grade endometrial cancer. Exemestane may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth.
PRIMARY OBJECTIVE:

      I. To determine if there is a decrease in proliferation index, measured by Ki-67 expression,
      in complex atypical hyperplasia (CAH)/endometrial intraepithelial neoplasia (EIN) or low
      grade (grade 1 and grade 2) endometrial cancer cells from baseline to post-exemestane
      treatment.

      SECONDARY OBJECTIVES:

      I. Circulating serum estradiol and progesterone. II. Pathological response (regression of
      CAH/EIN or low grade [grade 1 and grade 2] endometrial carcinoma).

      III. Tissue biomarkers. IV. Deoxyribonucleic acid (DNA) mutational analysis through next
      generation sequencing and methylation status of endometrial tumor.

      V. Protein markers via tampon recovery before and after treatment. VI. DNA markers via tampon
      recovery. VII. Safety and adverse effects of treatment. VIII. Comparison of Ki-67 expression
      changes between study subjects and a historical cohort.

      IX. Evaluation of the levels of exemestane in the plasma samples pre and post treatment.

      OUTLINE:

      Patients receive exemestane orally (PO) once daily (QD) over 21-42 days in the absence of
      disease progression or unaccepted toxicity. Patients undergo standard of care surgery between
      days 22-43.

      After completion of study treatment, patients with unresolved adverse events on day of
      surgery are followed up periodically.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Change in tumor proliferation
time frame: Baseline up to 7 months
description: Will be measured by change in Ki-67 expression. Will evaluate the change from baseline to post-exposure in absolute change in percent Ki-67 using one-sample Student's t-test or Wilcoxon signed-rank test, as appropriate.
measure: Changes in circulating serum estradiol
time frame: Baseline up to 7 months
measure: Changes in circulating serum progesterone
time frame: Baseline up to 7 months
measure: Pathological response to exemestane
time frame: Up to 7 months
description: Will assess regression of complex atypical hyperplasia/endometrial intraepithelial neoplasia and low grade (grade 1 and grade 2) endometrial carcinoma.
measure: Tissue marker analysis
time frame: Up to 7 months
description: Will assess apoptosis (cleaved caspase 3), proliferation (cyclin D1), insulin pathway (pAKT, IGF-1R), and endocrine regulation (estrogen receptor/progesterone receptor/androgen receptor).
measure: Deoxyribonucleic acid (DNA) mutational analysis
time frame: Up to 7 months
description: Will be analyzed by next generation sequencing.
measure: Methylation status of endometrial tumor
time frame: Up to 7 months
measure: Protein and DNA markers
time frame: Up to 7 months
description: Will be assessed via tampon recovery pre and post exemestane treatment.
measure: Ki-67 expression
time frame: Up to 7 months
description: Will compare Ki-67 expression between participants samples and historically matched samples.
measure: Plasma levels of exemestane
time frame: Up to 7 months
description: Will evaluate plasma levels of exemestane pre and post treatment.
arm group label: Treatment (exemestane)
arm group type: Experimental
description: Patients receive exemestane PO QD over 21-42 days in the absence of disease progression or unaccepted toxicity. Patients undergo standard of care surgery between days 22-43.
intervention type: Drug
intervention name: Exemestane
description: Given PO
arm group label: Treatment (exemestane)
other name: Aromasin
other name: FCE-24304
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (exemestane)
intervention type: Other
intervention name: Pharmacokinetic Study
description: Correlative studies
arm group label: Treatment (exemestane)
other name: PHARMACOKINETIC
other name: PK Study
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Treatment (exemestane)
criteria: 
gender: Female
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Britt K Erickson
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
facility: 
facility: 
country: United States
country: Italy
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Endometrial Neoplasms
mesh term: Neoplasms
mesh term: Carcinoma in Situ
mesh term: Carcinoma, Endometrioid
mesh term: Endometrial Hyperplasia
mesh term: Hyperplasia
mesh term: Exemestane
provided document: 