<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/NCT03018249</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-00058</org_study_id>
    <secondary_id>NCI-2017-00058</secondary_id>
    <secondary_id>NRG-GY011</secondary_id>
    <secondary_id>NRG-GY011</secondary_id>
    <secondary_id>NRG-GY011</secondary_id>
    <secondary_id>U10CA180868</secondary_id>
    <nct_id>NCT03018249</nct_id>
  </id_info>
  <brief_title>Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer</brief_title>
  <official_title>A Randomized Surgical Window Pilot Investigation of the Relationship of Short Term Medroxyprogesterone Acetate (NSC #26386) Compared to Medroxyprogesterone Acetate Plus Entinostat (NSC #706995) on the Morphologic, Biochemical, and Molecular Changes in Primary Endometrioid Adenocarcinoma of the Uterine Corpus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NRG Oncology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</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 randomized surgical window trial evaluates the effect of adding entinostat to&#xD;
      medroxyprogesterone acetate before surgery works on progesterone receptors on endometrioid&#xD;
      endometrial tumors. Medroxyprogesterone acetate is a progesterone, a hormone produced by body&#xD;
      normally. Entinostat may stop the growth of tumor cells by blocking some of the enzymes&#xD;
      needed for cell growth. Giving medroxyprogesterone acetate with or without entinostat may&#xD;
      effect tumors from endometrioid endometrial cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine whether the addition of the histone deacetylase inhibitor, entinostat, in&#xD;
      combination with medroxyprogesterone acetate in the pre-operative setting results in&#xD;
      up-regulation of activated progesterone receptors (PR) compared to medroxyprogesterone&#xD;
      acetate alone.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the response rate (as measured by cellular morphology and proliferation) and&#xD;
      change in activated receptor levels with the addition of entinostat at the time of&#xD;
      hysterectomy.&#xD;
&#xD;
      OUTLINE: Two arms were randomly allocated to eligible patients with equal probability.&#xD;
&#xD;
      ARM I: Patients receive medroxyprogesterone acetate intramuscularly (IM) on day 1 and undergo&#xD;
      hysterectomy between days 21-24.&#xD;
&#xD;
      ARM II: Patients receive medroxyprogesterone acetate IM on day 1 and entinostat orally (PO)&#xD;
      on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 11, 2017</start_date>
  <completion_date type="Actual">March 12, 2021</completion_date>
  <primary_completion_date type="Actual">April 18, 2018</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)</measure>
    <time_frame>Specimens were collected at hysterectomy on day 21-24 and analyzed in batch.</time_frame>
    <description>The H-score is defined as the percent cells staining positive (0-100) multiplied by the staining intensity (0, 1, 2 or 3) measured in the tumor by immunohistochemistry and averaged over 3 reviewers. This score can range from 0 to 300. In general, PRs are expected to decrease in response to medroxyprogesterone acetate. It was hypothesized that entinostat would mitigate the decrease in PR relative to the medroxyprogesterone acetate only arm post treatment. Higher PR H-scores post treatment in the arm with entinostat relative to the medroxyprogesterone alone arm would be consistent with this hypothesis. Arm II was thought to result in higher scores which was expected to have a more favorable outcome when treated with MPA therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Histologic Response</measure>
    <time_frame>Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.</time_frame>
    <description>Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. A histologic response was defined as either the absence of identifiable adenocarcinoma in the hysterectomy specimen section (complete) or, subjectively, as the presence of a complex proliferation of glands that retain the architectural characteristics of adenocarcinoma, but with features of secretion, decreased nuclear stratification, or the presence of eosinophilic, squamous or mucinous metaplasia, when this was absent in the initial sample (partial).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Participants With a Ki67 Response</measure>
    <time_frame>Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.</time_frame>
    <description>A response was defined as a decrease in Ki-67 protein expression in tumor from pre- to post-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE)</measure>
    <time_frame>Up to 45 days after surgery</time_frame>
    <description>Maximum grade of physician assessed adverse events reported during treatment and up to 45 days after surgery. Grades start with 1 which is considered mild through grade 5 which is death. Participants on this study had adverse event grades up to grade 3 which is considered moderately severe.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mean Post-treatment Tumor Estrogen Receptor Score</measure>
    <time_frame>Up to 3 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Co-expression of PR, Ki67, and p21</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Will be compared between the arms.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma</condition>
  <condition>FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma</condition>
  <condition>FIGO Grade 3 Endometrial Endometrioid Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (medroxyprogesterone acetate, hysterectomy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entinostat</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)</arm_group_label>
    <other_name>HDAC inhibitor SNDX-275</other_name>
    <other_name>MS 27-275</other_name>
    <other_name>MS-275</other_name>
    <other_name>SNDX-275</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hysterectomy</intervention_name>
    <description>Undergo hysterectomy</description>
    <arm_group_label>Arm I (medroxyprogesterone acetate, hysterectomy)</arm_group_label>
    <arm_group_label>Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)</arm_group_label>
    <other_name>Hysterectomy NOS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (medroxyprogesterone acetate, hysterectomy)</arm_group_label>
    <arm_group_label>Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Medroxyprogesterone Acetate</intervention_name>
    <description>Given IM</description>
    <arm_group_label>Arm I (medroxyprogesterone acetate, hysterectomy)</arm_group_label>
    <arm_group_label>Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)</arm_group_label>
    <other_name>Amen</other_name>
    <other_name>Aragest</other_name>
    <other_name>Ciclotal</other_name>
    <other_name>Clinofem</other_name>
    <other_name>Clinovir</other_name>
    <other_name>Cycrin</other_name>
    <other_name>Depo-Clinovir</other_name>
    <other_name>Depo-Provera</other_name>
    <other_name>Depot-Medroxyprogestereone Acetate</other_name>
    <other_name>Farlutal</other_name>
    <other_name>G-Farlutal</other_name>
    <other_name>Gestapuran</other_name>
    <other_name>Hysron</other_name>
    <other_name>Lutoral</other_name>
    <other_name>Medroxyprogesterone 17-Acetate</other_name>
    <other_name>Medroxyprogesteroni Acetas</other_name>
    <other_name>Methylacetoxyprogesterone</other_name>
    <other_name>Metipregnone</other_name>
    <other_name>MPA</other_name>
    <other_name>Nadigest</other_name>
    <other_name>Nadigest (vet)</other_name>
    <other_name>Nidaxin</other_name>
    <other_name>Nidaxin (vet)</other_name>
    <other_name>Oragest</other_name>
    <other_name>Perlutex</other_name>
    <other_name>Prodasone</other_name>
    <other_name>Provera</other_name>
    <other_name>Sodelut G</other_name>
    <other_name>Veramix</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have a histologically proven diagnosis of endometrioid endometrial&#xD;
             adenocarcinoma by endometrial curettage or biopsy within 8 weeks prior to&#xD;
             registration; central pathology review will be required as part of the study but not&#xD;
             for registration purposes&#xD;
&#xD;
          -  History/physical examination within 42 +/- 5 days of planned surgical procedure (18-21&#xD;
             days from day 1); further protocol-specific assessments&#xD;
&#xD;
          -  The trial is open only to women with primary endometrioid adenocarcinoma of the&#xD;
             uterine corpus (all histologic grades and stages) who are planned and appropriate for&#xD;
             primary surgical treatment to include removal of the uterine corpus via any surgical&#xD;
             modality; the patient must be considered a suitable surgical candidate&#xD;
&#xD;
          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0, 1, 2, or 3 within 28 days prior to registration&#xD;
&#xD;
          -  Formalin-fixed, paraffin-embedded tumor tissue from the biopsy or curettage must be&#xD;
             submitted along with the corresponding pathology report&#xD;
&#xD;
          -  Platelets &gt;= 100,000/ul&#xD;
&#xD;
          -  Granulocytes (ANC) &gt;= 1,500/ul&#xD;
&#xD;
          -  Creatinine =&lt; 1.6 mg/dl&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =&lt; 3 x&#xD;
             upper limits of normal&#xD;
&#xD;
          -  Bilirubin within institutional normal limits&#xD;
&#xD;
          -  The patient must provide study-specific informed consent and authorization permitting&#xD;
             release of personal health information prior to study entry&#xD;
&#xD;
          -  Any patients of childbearing potential must have a negative pregnancy test&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with any non-endometrioid histology (such as serous, clear cell, or&#xD;
             carcinosarcoma)&#xD;
&#xD;
          -  Patients who have received prior progestin or anti-estrogen therapy during the 3&#xD;
             months before the diagnosis of endometrioid adenocarcinoma of the uterine corpus is&#xD;
             established; estrogen therapy alone is allowed&#xD;
&#xD;
          -  Patients with ECOG performance grade of 4&#xD;
&#xD;
          -  Patients with history of thrombophlebitis within the past 2 years or ongoing&#xD;
             thromboembolic disorders&#xD;
&#xD;
          -  Patients who have previously received systemic, radiation or other treatment for&#xD;
             uterine cancer&#xD;
&#xD;
          -  Patients for whom formalin-fixed, paraffin-embedded tumor tissue from the biopsy or&#xD;
             curettage is unavailable&#xD;
&#xD;
          -  Patients must not have previously received a non Food and Drug Administration (FDA)&#xD;
             approved histone deacetylase (HDAC) inhibitor in a clinical trial setting (entinostat,&#xD;
             belinostat)&#xD;
&#xD;
          -  Patients must not be currently taking or have ever taken vorinostat (Zolinza, Merck),&#xD;
             panobinostat (Farydak, Novartis) or romidepsin (Istodax, Gloucester Pharmaceuticals)&#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>Linda R Duska</last_name>
    <role>Principal Investigator</role>
    <affiliation>NRG Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHI Saint Vincent Cancer Center Hot Springs</name>
      <address>
        <city>Hot Springs</city>
        <state>Arkansas</state>
        <zip>71913</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Muir Medical Center-Concord Campus</name>
      <address>
        <city>Concord</city>
        <state>California</state>
        <zip>94520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Muir Medical Center-Walnut Creek</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Aurora</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boulder Community Hospital</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Boulder</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penrose-Saint Francis Healthcare</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Penrose</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Denver Health Medical Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health-Main Campus</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Women's Imaging Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Porter Adventist Hospital</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Blood Cancer Institute</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presbyterian - Saint Lukes Medical Center - Health One</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Midtown</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCL Health Saint Joseph Hospital</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Rose</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rose Medical Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center</name>
      <address>
        <city>Durango</city>
        <state>Colorado</state>
        <zip>81301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Oncology PC</name>
      <address>
        <city>Durango</city>
        <state>Colorado</state>
        <zip>81301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mountain Blue Cancer Care Center - Swedish</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mountain Blue Cancer Care Center</name>
      <address>
        <city>Golden</city>
        <state>Colorado</state>
        <zip>80401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health-Western Hematology Oncology</name>
      <address>
        <city>Golden</city>
        <state>Colorado</state>
        <zip>80401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Colorado Medical Center</name>
      <address>
        <city>Greeley</city>
        <state>Colorado</state>
        <zip>80631</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Lakewood</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Anthony Hospital</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Littleton</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Littleton Adventist Hospital</name>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Sky Ridge</name>
      <address>
        <city>Lone Tree</city>
        <state>Colorado</state>
        <zip>80124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Longmont United Hospital</name>
      <address>
        <city>Longmont</city>
        <state>Colorado</state>
        <zip>80501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Longmont</name>
      <address>
        <city>Longmont</city>
        <state>Colorado</state>
        <zip>80501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McKee Medical Center</name>
      <address>
        <city>Loveland</city>
        <state>Colorado</state>
        <zip>80539</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parker Adventist Hospital</name>
      <address>
        <city>Parker</city>
        <state>Colorado</state>
        <zip>80138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Parker</name>
      <address>
        <city>Parker</city>
        <state>Colorado</state>
        <zip>80138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Mary Corwin Medical Center</name>
      <address>
        <city>Pueblo</city>
        <state>Colorado</state>
        <zip>81004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers - Pueblo</name>
      <address>
        <city>Pueblo</city>
        <state>Colorado</state>
        <zip>81008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health-Northern Hematology Oncology</name>
      <address>
        <city>Thornton</city>
        <state>Colorado</state>
        <zip>80260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers-Thornton</name>
      <address>
        <city>Thornton</city>
        <state>Colorado</state>
        <zip>80260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCL Health Lutheran Medical Center</name>
      <address>
        <city>Wheat Ridge</city>
        <state>Colorado</state>
        <zip>80033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beebe Medical Center</name>
      <address>
        <city>Lewes</city>
        <state>Delaware</state>
        <zip>19958</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Delaware Clinical and Laboratory Physicians PA</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helen F Graham Cancer Center</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology Hematology Consultants PA</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Health System-Christiana Hospital</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beebe Health Campus</name>
      <address>
        <city>Rehoboth Beach</city>
        <state>Delaware</state>
        <zip>19971</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TidalHealth Nanticoke / Allen Cancer Center</name>
      <address>
        <city>Seaford</city>
        <state>Delaware</state>
        <zip>19973</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Health System-Wilmington Hospital</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sacred Heart Hospital</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kootenai Medical Center</name>
      <address>
        <city>Coeur d'Alene</city>
        <state>Idaho</state>
        <zip>83814</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kootenai Cancer Center</name>
      <address>
        <city>Post Falls</city>
        <state>Idaho</state>
        <zip>83854</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kootenai Cancer Clinic</name>
      <address>
        <city>Sandpoint</city>
        <state>Idaho</state>
        <zip>83864</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medicine Lake Forest Hospital</name>
      <address>
        <city>Lake Forest</city>
        <state>Illinois</state>
        <zip>60045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Good Samaritan Regional Health Center</name>
      <address>
        <city>Mount Vernon</city>
        <state>Illinois</state>
        <zip>62864</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Comprehensive Cancer Center at Silver Cross</name>
      <address>
        <city>New Lenox</city>
        <state>Illinois</state>
        <zip>60451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medicine-Orland Park</name>
      <address>
        <city>Orland Park</city>
        <state>Illinois</state>
        <zip>60462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkview Hospital Randallia</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology and Hematology Associates-West Des Moines</name>
      <address>
        <city>Clive</city>
        <state>Iowa</state>
        <zip>50325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Cancer Center-West Lakes</name>
      <address>
        <city>Clive</city>
        <state>Iowa</state>
        <zip>50325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alegent Health Mercy Hospital</name>
      <address>
        <city>Council Bluffs</city>
        <state>Iowa</state>
        <zip>51503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greater Regional Medical Center</name>
      <address>
        <city>Creston</city>
        <state>Iowa</state>
        <zip>50801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Oncology and Hematology Associates-Laurel</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center - Des Moines</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center-West Lakes</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50266</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital-Westwood Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Flaget Memorial Hospital</name>
      <address>
        <city>Bardstown</city>
        <state>Kentucky</state>
        <zip>40004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Commonwealth Cancer Center-Corbin</name>
      <address>
        <city>Corbin</city>
        <state>Kentucky</state>
        <zip>40701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Radiation Oncology Resource Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Hospital East</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph London</name>
      <address>
        <city>London</city>
        <state>Kentucky</state>
        <zip>40741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saints Mary and Elizabeth Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish Hospital Medical Center Northeast</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40245</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jewish Hospital Medical Center South</name>
      <address>
        <city>Shepherdsville</city>
        <state>Kentucky</state>
        <zip>40165</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana State University Health Science Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center Jefferson</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willis-Knighton Medical and Cancer Center</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greater Baltimore Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Ridges Hospital</name>
      <address>
        <city>Burnsville</city>
        <state>Minnesota</state>
        <zip>55337</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital</name>
      <address>
        <city>Coon Rapids</city>
        <state>Minnesota</state>
        <zip>55433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Southdale Hospital</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unity Hospital</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Clinics and Surgery Center Maple Grove</name>
      <address>
        <city>Maple Grove</city>
        <state>Minnesota</state>
        <zip>55369</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology PA-Maplewood</name>
      <address>
        <city>Maplewood</city>
        <state>Minnesota</state>
        <zip>55109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint John's Hospital - Healtheast</name>
      <address>
        <city>Maplewood</city>
        <state>Minnesota</state>
        <zip>55109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abbott-Northwestern Hospital</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hennepin County Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Partners Inc</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Ulm Medical Center</name>
      <address>
        <city>New Ulm</city>
        <state>Minnesota</state>
        <zip>56073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Memorial Medical Health Center</name>
      <address>
        <city>Robbinsdale</city>
        <state>Minnesota</state>
        <zip>55422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Park Nicollet Clinic - Saint Louis Park</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regions Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>United Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Regional Medical Center</name>
      <address>
        <city>Shakopee</city>
        <state>Minnesota</state>
        <zip>55379</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakeview Hospital</name>
      <address>
        <city>Stillwater</city>
        <state>Minnesota</state>
        <zip>55082</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ridgeview Medical Center</name>
      <address>
        <city>Waconia</city>
        <state>Minnesota</state>
        <zip>55387</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rice Memorial Hospital</name>
      <address>
        <city>Willmar</city>
        <state>Minnesota</state>
        <zip>56201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Hematology PA-Woodbury</name>
      <address>
        <city>Woodbury</city>
        <state>Minnesota</state>
        <zip>55125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Lakes Medical Center</name>
      <address>
        <city>Wyoming</city>
        <state>Minnesota</state>
        <zip>55092</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Louis Cancer and Breast Institute-Ballwin</name>
      <address>
        <city>Ballwin</city>
        <state>Missouri</state>
        <zip>63011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Care Cancer Center - Bolivar</name>
      <address>
        <city>Bolivar</city>
        <state>Missouri</state>
        <zip>65613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cox Cancer Center Branson</name>
      <address>
        <city>Branson</city>
        <state>Missouri</state>
        <zip>65616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Health System</name>
      <address>
        <city>Joplin</city>
        <state>Missouri</state>
        <zip>64804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Joplin</name>
      <address>
        <city>Joplin</city>
        <state>Missouri</state>
        <zip>64804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Delbert Day Cancer Institute at PCRMC</name>
      <address>
        <city>Rolla</city>
        <state>Missouri</state>
        <zip>65401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Clinic-Rolla-Cancer and Hematology</name>
      <address>
        <city>Rolla</city>
        <state>Missouri</state>
        <zip>65401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heartland Regional Medical Center</name>
      <address>
        <city>Saint Joseph</city>
        <state>Missouri</state>
        <zip>64506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Louis Cancer and Breast Institute-South City</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Saint Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Springfield</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CoxHealth South Hospital</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Washington</name>
      <address>
        <city>Washington</city>
        <state>Missouri</state>
        <zip>63090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Hospital of Anaconda</name>
      <address>
        <city>Anaconda</city>
        <state>Montana</state>
        <zip>59711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Billings Clinic Cancer Center</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bozeman Deaconess Hospital</name>
      <address>
        <city>Bozeman</city>
        <state>Montana</state>
        <zip>59715</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Benefis Healthcare- Sletten Cancer Institute</name>
      <address>
        <city>Great Falls</city>
        <state>Montana</state>
        <zip>59405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Great Falls Clinic</name>
      <address>
        <city>Great Falls</city>
        <state>Montana</state>
        <zip>59405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Peter's Community Hospital</name>
      <address>
        <city>Helena</city>
        <state>Montana</state>
        <zip>59601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kalispell Regional Medical Center</name>
      <address>
        <city>Kalispell</city>
        <state>Montana</state>
        <zip>59901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Medical Hospital</name>
      <address>
        <city>Missoula</city>
        <state>Montana</state>
        <zip>59804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Health Saint Francis</name>
      <address>
        <city>Grand Island</city>
        <state>Nebraska</state>
        <zip>68803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heartland Hematology and Oncology</name>
      <address>
        <city>Kearney</city>
        <state>Nebraska</state>
        <zip>68845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Health Good Samaritan</name>
      <address>
        <city>Kearney</city>
        <state>Nebraska</state>
        <zip>68847</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Elizabeth Regional Medical Center</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alegent Health Immanuel Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology and Oncology Consultants PC</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alegent Health Bergan Mercy Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alegent Health Lakeside Hospital</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Creighton University Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midlands Community Hospital</name>
      <address>
        <city>Papillion</city>
        <state>Nebraska</state>
        <zip>68046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Center of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's Cancer Care Associates LLC</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State University of New York Downstate Medical Center</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Strecker Cancer Center-Belpre</name>
      <address>
        <city>Belpre</city>
        <state>Ohio</state>
        <zip>45714</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adena Regional Medical Center</name>
      <address>
        <city>Chillicothe</city>
        <state>Ohio</state>
        <zip>45601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Good Samaritan Hospital - Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bethesda North Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TriHealth Cancer Institute-Westside</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45247</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TriHealth Cancer Institute-Anderson</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45255</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Carmel East Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbus Oncology and Hematology Associates Inc</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riverside Methodist Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grant Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Mark H Zangmeister Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Carmel Health Center West</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43222</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Doctors Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Delaware Health Center-Grady Cancer Center</name>
      <address>
        <city>Delaware</city>
        <state>Ohio</state>
        <zip>43015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Delaware Radiation Oncology</name>
      <address>
        <city>Delaware</city>
        <state>Ohio</state>
        <zip>43015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grady Memorial Hospital</name>
      <address>
        <city>Delaware</city>
        <state>Ohio</state>
        <zip>43015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairfield Medical Center</name>
      <address>
        <city>Lancaster</city>
        <state>Ohio</state>
        <zip>43130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OhioHealth Mansfield Hospital</name>
      <address>
        <city>Mansfield</city>
        <state>Ohio</state>
        <zip>44903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marietta Memorial Hospital</name>
      <address>
        <city>Marietta</city>
        <state>Ohio</state>
        <zip>45750</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OhioHealth Marion General Hospital</name>
      <address>
        <city>Marion</city>
        <state>Ohio</state>
        <zip>43302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Knox Community Hospital</name>
      <address>
        <city>Mount Vernon</city>
        <state>Ohio</state>
        <zip>43050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Licking Memorial Hospital</name>
      <address>
        <city>Newark</city>
        <state>Ohio</state>
        <zip>43055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newark Radiation Oncology</name>
      <address>
        <city>Newark</city>
        <state>Ohio</state>
        <zip>43055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Ohio Medical Center</name>
      <address>
        <city>Portsmouth</city>
        <state>Ohio</state>
        <zip>45662</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Ann's Hospital</name>
      <address>
        <city>Westerville</city>
        <state>Ohio</state>
        <zip>43081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Genesis Healthcare System Cancer Care Center</name>
      <address>
        <city>Zanesville</city>
        <state>Ohio</state>
        <zip>43701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Oklahoma City</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oklahoma Cancer Specialists and Research Institute-Tulsa</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abington Memorial Hospital</name>
      <address>
        <city>Abington</city>
        <state>Pennsylvania</state>
        <zip>19001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Heritage Valley Health System Beaver</name>
      <address>
        <city>Beaver</city>
        <state>Pennsylvania</state>
        <zip>15009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Health System-Concord Health Center</name>
      <address>
        <city>Chadds Ford</city>
        <state>Pennsylvania</state>
        <zip>19317</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Centers - Arnold Palmer Pavilion</name>
      <address>
        <city>Greensburg</city>
        <state>Pennsylvania</state>
        <zip>15601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center-Cancer Center Hazleton</name>
      <address>
        <city>Hazleton</city>
        <state>Pennsylvania</state>
        <zip>18201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Johnstown/John P. Murtha Regional Cancer Center</name>
      <address>
        <city>Johnstown</city>
        <state>Pennsylvania</state>
        <zip>15901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Oncology-Lewisburg</name>
      <address>
        <city>Lewisburg</city>
        <state>Pennsylvania</state>
        <zip>17837</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lewistown Hospital</name>
      <address>
        <city>Lewistown</city>
        <state>Pennsylvania</state>
        <zip>17044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Center at UPMC McKeesport</name>
      <address>
        <city>McKeesport</city>
        <state>Pennsylvania</state>
        <zip>15132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Coraopolis/Heritage Valley Radiation Oncology</name>
      <address>
        <city>Moon</city>
        <state>Pennsylvania</state>
        <zip>15108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Magee Womens Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Presbyterian Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Saint Margaret</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute (UPCI)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Shadyside Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Passavant Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC-Saint Clair Hospital Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15243</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Cancer Services-Pottsville</name>
      <address>
        <city>Pottsville</city>
        <state>Pennsylvania</state>
        <zip>17901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Medical Center</name>
      <address>
        <city>Scranton</city>
        <state>Pennsylvania</state>
        <zip>18510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Oncology-Selinsgrove</name>
      <address>
        <city>Selinsgrove</city>
        <state>Pennsylvania</state>
        <zip>17870</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Center at UPMC Northwest</name>
      <address>
        <city>Seneca</city>
        <state>Pennsylvania</state>
        <zip>16346</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Group</name>
      <address>
        <city>State College</city>
        <state>Pennsylvania</state>
        <zip>16801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Uniontown Hospital Radiation Oncology</name>
      <address>
        <city>Uniontown</city>
        <state>Pennsylvania</state>
        <zip>15401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Washington Hospital Radiation Oncology</name>
      <address>
        <city>Washington</city>
        <state>Pennsylvania</state>
        <zip>15301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geisinger Wyoming Valley/Henry Cancer Center</name>
      <address>
        <city>Wilkes-Barre</city>
        <state>Pennsylvania</state>
        <zip>18711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women and Infants Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Laurens</name>
      <address>
        <city>Clinton</city>
        <state>South Carolina</state>
        <zip>29325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Easley</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <zip>29640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Butternut</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Faris</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Greenville Memorial Hospital</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Eastside</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Greer</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29650</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Seneca</name>
      <address>
        <city>Seneca</city>
        <state>South Carolina</state>
        <zip>29672</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Cancer Institute - Spartanburg</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Hospital</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt-Ingram Cancer Center Cool Springs</name>
      <address>
        <city>Franklin</city>
        <state>Tennessee</state>
        <zip>37067</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Medicine Center of Chattanooga-Hixson</name>
      <address>
        <city>Hixson</city>
        <state>Tennessee</state>
        <zip>37343</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt Breast Center at One Hundred Oaks</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University/Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial GYN Plus</name>
      <address>
        <city>Ooltewah</city>
        <state>Tennessee</state>
        <zip>37363</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Regional Cancer Center</name>
      <address>
        <city>Bryan</city>
        <state>Texas</state>
        <zip>77802</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Cancer Center</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harrison HealthPartners Hematology and Oncology-Bremerton</name>
      <address>
        <city>Bremerton</city>
        <state>Washington</state>
        <zip>98310</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harrison Medical Center</name>
      <address>
        <city>Bremerton</city>
        <state>Washington</state>
        <zip>98310</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Highline Medical Center-Main Campus</name>
      <address>
        <city>Burien</city>
        <state>Washington</state>
        <zip>98166</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Elizabeth Hospital</name>
      <address>
        <city>Enumclaw</city>
        <state>Washington</state>
        <zip>98022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Hospital</name>
      <address>
        <city>Federal Way</city>
        <state>Washington</state>
        <zip>98003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Clare Hospital</name>
      <address>
        <city>Lakewood</city>
        <state>Washington</state>
        <zip>98499</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harrison HealthPartners Hematology and Oncology-Poulsbo</name>
      <address>
        <city>Poulsbo</city>
        <state>Washington</state>
        <zip>98370</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franciscan Research Center-Northwest Medical Plaza</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Medical Specialties PLLC</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Western Wisconsin</name>
      <address>
        <city>New Richmond</city>
        <state>Wisconsin</state>
        <zip>54017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cheyenne Regional Medical Center-West</name>
      <address>
        <city>Cheyenne</city>
        <state>Wyoming</state>
        <zip>82001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Billings Clinic-Cody</name>
      <address>
        <city>Cody</city>
        <state>Wyoming</state>
        <zip>82414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Welch Cancer Center</name>
      <address>
        <city>Sheridan</city>
        <state>Wyoming</state>
        <zip>82801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <results_first_submitted>March 3, 2021</results_first_submitted>
  <results_first_submitted_qc>May 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 2, 2021</results_first_posted>
  <last_update_submitted>November 15, 2021</last_update_submitted>
  <last_update_submitted_qc>November 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2021</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>Carcinoma, Endometrioid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Medroxyprogesterone Acetate</mesh_term>
    <mesh_term>Entinostat</mesh_term>
    <mesh_term>Medroxyprogesterone</mesh_term>
    <mesh_term>Histone Deacetylase Inhibitors</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 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/49/NCT03018249/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was open to accrual on 8/17/2017. The first patient was enrolled on October 11, 2017. The study closed to accrual 4 months later on 2/9/2018 after 50 patients were enrolled across 13 unique sites.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA</title>
          <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat</title>
          <description>Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Eligible patients</population>
      <group_list>
        <group group_id="B1">
          <title>Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA</title>
          <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
        </group>
        <group group_id="B2">
          <title>Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat</title>
          <description>Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="25"/>
            <count group_id="B3" value="50"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>30-49 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50-59 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-69 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-99 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </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="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Participants with Endometrioid Cell Type Cancer</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)</title>
        <description>The H-score is defined as the percent cells staining positive (0-100) multiplied by the staining intensity (0, 1, 2 or 3) measured in the tumor by immunohistochemistry and averaged over 3 reviewers. This score can range from 0 to 300. In general, PRs are expected to decrease in response to medroxyprogesterone acetate. It was hypothesized that entinostat would mitigate the decrease in PR relative to the medroxyprogesterone acetate only arm post treatment. Higher PR H-scores post treatment in the arm with entinostat relative to the medroxyprogesterone alone arm would be consistent with this hypothesis. Arm II was thought to result in higher scores which was expected to have a more favorable outcome when treated with MPA therapy.</description>
        <time_frame>Specimens were collected at hysterectomy on day 21-24 and analyzed in batch.</time_frame>
        <population>Randomized, treated, evaluable specimen. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA</title>
            <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat</title>
            <description>Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)</title>
          <description>The H-score is defined as the percent cells staining positive (0-100) multiplied by the staining intensity (0, 1, 2 or 3) measured in the tumor by immunohistochemistry and averaged over 3 reviewers. This score can range from 0 to 300. In general, PRs are expected to decrease in response to medroxyprogesterone acetate. It was hypothesized that entinostat would mitigate the decrease in PR relative to the medroxyprogesterone acetate only arm post treatment. Higher PR H-scores post treatment in the arm with entinostat relative to the medroxyprogesterone alone arm would be consistent with this hypothesis. Arm II was thought to result in higher scores which was expected to have a more favorable outcome when treated with MPA therapy.</description>
          <population>Randomized, treated, evaluable specimen. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.</population>
          <units>units 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="22"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.6" spread="64.8"/>
                    <measurement group_id="O2" value="42.7" spread="49.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.87</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Histologic Response</title>
        <description>Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. A histologic response was defined as either the absence of identifiable adenocarcinoma in the hysterectomy specimen section (complete) or, subjectively, as the presence of a complex proliferation of glands that retain the architectural characteristics of adenocarcinoma, but with features of secretion, decreased nuclear stratification, or the presence of eosinophilic, squamous or mucinous metaplasia, when this was absent in the initial sample (partial).</description>
        <time_frame>Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.</time_frame>
        <population>Randomized, treated, evaluable pre and post treatment specimen available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA</title>
            <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat</title>
            <description>Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Histologic Response</title>
          <description>Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. A histologic response was defined as either the absence of identifiable adenocarcinoma in the hysterectomy specimen section (complete) or, subjectively, as the presence of a complex proliferation of glands that retain the architectural characteristics of adenocarcinoma, but with features of secretion, decreased nuclear stratification, or the presence of eosinophilic, squamous or mucinous metaplasia, when this was absent in the initial sample (partial).</description>
          <population>Randomized, treated, evaluable pre and post treatment specimen available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group 2.</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="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-25</ci_lower_limit>
            <ci_upper_limit>30</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Participants With a Ki67 Response</title>
        <description>A response was defined as a decrease in Ki-67 protein expression in tumor from pre- to post-treatment.</description>
        <time_frame>Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.</time_frame>
        <population>Randomized, treated, evaluable pre and post treatment specimens available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA</title>
            <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat</title>
            <description>Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Participants With a Ki67 Response</title>
          <description>A response was defined as a decrease in Ki-67 protein expression in tumor from pre- to post-treatment.</description>
          <population>Randomized, treated, evaluable pre and post treatment specimens available. There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. There was one participant with an inevaluable pre-treatment slide. There were two additional patients with insufficient tumor post-treatment and no slides were submitted; one in each reporting group. There was one additional patient with no specimens submitted in reporting group</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="22"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>21.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-16.7</ci_lower_limit>
            <ci_upper_limit>45.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE)</title>
        <description>Maximum grade of physician assessed adverse events reported during treatment and up to 45 days after surgery. Grades start with 1 which is considered mild through grade 5 which is death. Participants on this study had adverse event grades up to grade 3 which is considered moderately severe.</description>
        <time_frame>Up to 45 days after surgery</time_frame>
        <population>Eligible and Treated Patients</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA</title>
            <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat</title>
            <description>Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.</description>
          </group>
        </group_list>
        <measure>
          <title>The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE)</title>
          <description>Maximum grade of physician assessed adverse events reported during treatment and up to 45 days after surgery. Grades start with 1 which is considered mild through grade 5 which is death. Participants on this study had adverse event grades up to grade 3 which is considered moderately severe.</description>
          <population>Eligible and Treated Patients</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Mean Post-treatment Tumor Estrogen Receptor Score</title>
        <time_frame>Up to 3 years</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Co-expression of PR, Ki67, and p21</title>
        <description>Will be compared between the arms.</description>
        <time_frame>Up to 3 years</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From initiation of treatment up to 45 days post-surgery</time_frame>
      <desc>There were 2 participants in each reporting group who withdrew consent prior to treatment; no specimens were submitted for these patients. No AEs were reported.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm I (Medroxyprogesterone Acetate, Hysterectomy) MPA</title>
          <description>Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.</description>
        </group>
        <group group_id="E2">
          <title>Arm II (Medroxyprogesterone Acetate, Entinostat, Hysterectomy) MPA and Entinostat</title>
          <description>Medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Followed by hysterectomy between days 21-24.</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="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic Event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </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="14" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Injection Site Reaction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vaginal Discharge</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Vaginal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="23"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Linda Gedeon for Virginia Filiaci, PhD</name_or_title>
      <organization>NRG Oncology</organization>
      <phone>716-845-1169</phone>
      <email>linda.gedeon@roswellpark.org</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/NCT03018249
org study id: NCI-2017-00058
secondary id: NCI-2017-00058
secondary id: NRG-GY011
secondary id: NRG-GY011
secondary id: NRG-GY011
secondary id: U10CA180868
nct id: NCT03018249
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This randomized surgical window trial evaluates the effect of adding entinostat to
      medroxyprogesterone acetate before surgery works on progesterone receptors on endometrioid
      endometrial tumors. Medroxyprogesterone acetate is a progesterone, a hormone produced by body
      normally. Entinostat may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Giving medroxyprogesterone acetate with or without entinostat may
      effect tumors from endometrioid endometrial cancer.
PRIMARY OBJECTIVES:

      I. To determine whether the addition of the histone deacetylase inhibitor, entinostat, in
      combination with medroxyprogesterone acetate in the pre-operative setting results in
      up-regulation of activated progesterone receptors (PR) compared to medroxyprogesterone
      acetate alone.

      SECONDARY OBJECTIVES:

      I. To assess the response rate (as measured by cellular morphology and proliferation) and
      change in activated receptor levels with the addition of entinostat at the time of
      hysterectomy.

      OUTLINE: Two arms were randomly allocated to eligible patients with equal probability.

      ARM I: Patients receive medroxyprogesterone acetate intramuscularly (IM) on day 1 and undergo
      hysterectomy between days 21-24.

      ARM II: Patients receive medroxyprogesterone acetate IM on day 1 and entinostat orally (PO)
      on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)
time frame: Specimens were collected at hysterectomy on day 21-24 and analyzed in batch.
description: The H-score is defined as the percent cells staining positive (0-100) multiplied by the staining intensity (0, 1, 2 or 3) measured in the tumor by immunohistochemistry and averaged over 3 reviewers. This score can range from 0 to 300. In general, PRs are expected to decrease in response to medroxyprogesterone acetate. It was hypothesized that entinostat would mitigate the decrease in PR relative to the medroxyprogesterone acetate only arm post treatment. Higher PR H-scores post treatment in the arm with entinostat relative to the medroxyprogesterone alone arm would be consistent with this hypothesis. Arm II was thought to result in higher scores which was expected to have a more favorable outcome when treated with MPA therapy.
measure: Percentage of Participants With a Histologic Response
time frame: Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.
description: Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. Pre- and post-treatment slides for each patient were evaluated in pairs for complete or partial histologic response by one reviewer. A histologic response was defined as either the absence of identifiable adenocarcinoma in the hysterectomy specimen section (complete) or, subjectively, as the presence of a complex proliferation of glands that retain the architectural characteristics of adenocarcinoma, but with features of secretion, decreased nuclear stratification, or the presence of eosinophilic, squamous or mucinous metaplasia, when this was absent in the initial sample (partial).
measure: Percent of Participants With a Ki67 Response
time frame: Specimens were collected at initial diagnostic biopsy and at hysterectomy on day 21-24 and analyzed in batch.
description: A response was defined as a decrease in Ki-67 protein expression in tumor from pre- to post-treatment.
measure: The Frequency and Severity of CTCAE Version 4.0 Graded Adverse Events (AE)
time frame: Up to 45 days after surgery
description: Maximum grade of physician assessed adverse events reported during treatment and up to 45 days after surgery. Grades start with 1 which is considered mild through grade 5 which is death. Participants on this study had adverse event grades up to grade 3 which is considered moderately severe.
measure: Mean Post-treatment Tumor Estrogen Receptor Score
time frame: Up to 3 years
measure: Co-expression of PR, Ki67, and p21
time frame: Up to 3 years
description: Will be compared between the arms.
arm group label: Arm I (medroxyprogesterone acetate, hysterectomy)
arm group type: Active Comparator
description: Patients receive medroxyprogesterone acetate IM on day 1 and undergo hysterectomy between days 21-24.
arm group label: Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)
arm group type: Experimental
description: Patients receive medroxyprogesterone acetate IM on day 1 and entinostat PO on days 1, 8, and 15. Patients undergo hysterectomy between days 21-24.
intervention type: Drug
intervention name: Entinostat
description: Given PO
arm group label: Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)
other name: HDAC inhibitor SNDX-275
other name: MS 27-275
other name: MS-275
other name: SNDX-275
intervention type: Procedure
intervention name: Hysterectomy
description: Undergo hysterectomy
arm group label: Arm I (medroxyprogesterone acetate, hysterectomy)
arm group label: Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)
other name: Hysterectomy NOS
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (medroxyprogesterone acetate, hysterectomy)
arm group label: Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)
intervention type: Drug
intervention name: Medroxyprogesterone Acetate
description: Given IM
arm group label: Arm I (medroxyprogesterone acetate, hysterectomy)
arm group label: Arm II (medroxyprogesterone acetate, entinostat, hysterectomy)
other name: Amen
other name: Aragest
other name: Ciclotal
other name: Clinofem
other name: Clinovir
other name: Cycrin
other name: Depo-Clinovir
other name: Depo-Provera
other name: Depot-Medroxyprogestereone Acetate
other name: Farlutal
other name: G-Farlutal
other name: Gestapuran
other name: Hysron
other name: Lutoral
other name: Medroxyprogesterone 17-Acetate
other name: Medroxyprogesteroni Acetas
other name: Methylacetoxyprogesterone
other name: Metipregnone
other name: MPA
other name: Nadigest
other name: Nadigest (vet)
other name: Nidaxin
other name: Nidaxin (vet)
other name: Oragest
other name: Perlutex
other name: Prodasone
other name: Provera
other name: Sodelut G
other name: Veramix
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Linda R Duska
role: Principal Investigator
affiliation: NRG Oncology
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country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Carcinoma, Endometrioid
mesh term: Medroxyprogesterone Acetate
mesh term: Entinostat
mesh term: Medroxyprogesterone
mesh term: Histone Deacetylase Inhibitors
provided document: 
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 