<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/NCT04491682</url>
  </required_header>
  <id_info>
    <org_study_id>53211029-01</org_study_id>
    <nct_id>NCT04491682</nct_id>
  </id_info>
  <brief_title>Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia</brief_title>
  <official_title>Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To see if megestrol acetate plus rosuvastatin will be superior to reversing the endometrial&#xD;
      lesion to a normal endometrium than megestrol acetate alone in patients with atypical&#xD;
      endometrial hyperplasia (AEH). Considering the large sample size in RCT, we used Simon&#xD;
      two-stage design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After diagnosed of AEH by hysteroscopy, patients will be enrolled. Age, height, weight, waist&#xD;
      circumstances, blood pressure, basic history of infertility and blood pressure will be&#xD;
      collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), OGTT&#xD;
      2h blood glucose and insulin, blood lipids, SHBG, sex hormone levels, anti-müllerian&#xD;
      hormone(AMH), creatine kinase(CK) and renal/liver function tests will be performed before&#xD;
      treatment to evacuate their basic conditions. Each subject will receive body fat testing by&#xD;
      Inbody 520.&#xD;
&#xD;
      Patients are randomized to 1 of 2 treatment groups. Patients will receive MA 160 mg plus&#xD;
      rosuvastatin 10mg by mouth daily for at least 6 months. Then hysteroscopy will be used to&#xD;
      evaluate the endometrial condition every 3 months, and intra-operative findings will be&#xD;
      recorded. Complete response (CR) is defined as the reversion of endometrial atypical&#xD;
      hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as&#xD;
      regression to simple or complex hyperplasia without atypic; stable disease (SD) is defined as&#xD;
      the persistence of the disease; and progressive disease (PD) is defined as the appearance of&#xD;
      endometrial cancer in patients. Continuous therapies will be needed in PR or NR. Patients&#xD;
      with PD will be recommended for hysterectomy.&#xD;
&#xD;
      Two months of maintenance treatment will be recommended for patients with CR, and&#xD;
      participants will be followed up for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2020</start_date>
  <completion_date type="Actual">June 20, 2022</completion_date>
  <primary_completion_date type="Actual">June 20, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathological response rate</measure>
    <time_frame>12 to 16 weeks</time_frame>
    <description>From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 16 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pathological response rate</measure>
    <time_frame>28 to 32 weeks</time_frame>
    <description>From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 32 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathological response duration</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Pathological response duration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathological response rate classified by different blood lipid level</measure>
    <time_frame>Up to 32 weeks</time_frame>
    <description>Pathological response rate classified by different blood lipid level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity evaluation</measure>
    <time_frame>Up to 32 weeks</time_frame>
    <description>Toxicity evaluation according to CTCAE 5.0 version.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse rate</measure>
    <time_frame>up to 2 years after the therapy for each patient</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy rate</measure>
    <time_frame>up to 2 years after the therapy for each patient</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Atypical Endometrial Hyperplasia</condition>
  <arm_group>
    <arm_group_label>MA + Rosuvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive MA 160 mg and rosuvastatin 10 mg by mouth daily for at least 6 months.Then every 3 months, hysteroscopy will be used to evaluate the endometrial condition, and findings will be recorded.&#xD;
Due to personal reasons, it may not be possible to accept hysteroscopic evaluation every three months, then the longest duration will be 8 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Megestrol Acetate</intervention_name>
    <description>At a dosage of 160 mg/day</description>
    <arm_group_label>MA + Rosuvastatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin</intervention_name>
    <description>At a dosage of 10 mg/day</description>
    <arm_group_label>MA + Rosuvastatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a confirmed pathological diagnosis based upon hysteroscopy&#xD;
&#xD;
          -  Have a desire for remaining reproductive function or uterus&#xD;
&#xD;
          -  Good compliance with adjunctive treatment and follow-up&#xD;
&#xD;
          -  Abnormal blood lipid. At least meet one of the following five items:&#xD;
&#xD;
               1. Total cholesterol (TC) ≥ 5.2mmol/L (200mg/dL)&#xD;
&#xD;
               2. Low-density lipoprotein cholesterol (LDL-C) ≥ 3.4mmol/L (130mg/dL)&#xD;
&#xD;
               3. Fasting triglycerides (TG) ≥ 1.7mmol/L (150mg/dL)&#xD;
&#xD;
               4. High-density lipoprotein cholesterol (HDL-C) &lt;1.03mmol/L (40mg/dL)&#xD;
&#xD;
               5. Apo-lipoprotein-A (Apo-A) ≥ 1.0g/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute liver disease or liver tumor (benign or malignant) or renal dysfunction&#xD;
&#xD;
          -  Pregnancy or potential pregnancy&#xD;
&#xD;
          -  Under treatment of high-dose progestin therapy more than 1 months in recent 6 months&#xD;
&#xD;
          -  Confirmed diagnosis of any cancer in reproductive system&#xD;
&#xD;
          -  Acute severe disease such as stroke or heart infarction or a history of thrombosis&#xD;
             disease&#xD;
&#xD;
          -  Hypersensitivity or contradiction for using MA or statins&#xD;
&#xD;
          -  Already diagnosed with hyperlipidemia and using lipid-lowering drugs&#xD;
&#xD;
          -  With other factors of reproductive dysfunction;&#xD;
&#xD;
          -  Strong request for uterine removal or other conservative treatment&#xD;
&#xD;
          -  Smoker (&gt;15 cigarettes a day)&#xD;
&#xD;
          -  Drinker (&gt;20 grams a day)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xiaojun Chen</last_name>
    <role>Principal Investigator</role>
    <affiliation>Obstetrics and Gynecology Hospital, Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Obstetrics and Gynecology Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>August 25, 2022</last_update_submitted>
  <last_update_submitted_qc>August 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Obstetrics &amp; Gynecology Hospital of Fudan University</investigator_affiliation>
    <investigator_full_name>Xiaojun Chen</investigator_full_name>
    <investigator_title>Principle investigator</investigator_title>
  </responsible_party>
  <keyword>megestrol acetate</keyword>
  <keyword>rosuvastatin</keyword>
  <keyword>atypical endometrial hyperplasia</keyword>
  <keyword>conservative treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Hyperplasia</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Megestrol</mesh_term>
    <mesh_term>Megestrol Acetate</mesh_term>
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04491682
org study id: 53211029-01
nct id: NCT04491682
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To see if megestrol acetate plus rosuvastatin will be superior to reversing the endometrial
      lesion to a normal endometrium than megestrol acetate alone in patients with atypical
      endometrial hyperplasia (AEH). Considering the large sample size in RCT, we used Simon
      two-stage design.
After diagnosed of AEH by hysteroscopy, patients will be enrolled. Age, height, weight, waist
      circumstances, blood pressure, basic history of infertility and blood pressure will be
      collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), OGTT
      2h blood glucose and insulin, blood lipids, SHBG, sex hormone levels, anti-müllerian
      hormone(AMH), creatine kinase(CK) and renal/liver function tests will be performed before
      treatment to evacuate their basic conditions. Each subject will receive body fat testing by
      Inbody 520.

      Patients are randomized to 1 of 2 treatment groups. Patients will receive MA 160 mg plus
      rosuvastatin 10mg by mouth daily for at least 6 months. Then hysteroscopy will be used to
      evaluate the endometrial condition every 3 months, and intra-operative findings will be
      recorded. Complete response (CR) is defined as the reversion of endometrial atypical
      hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as
      regression to simple or complex hyperplasia without atypic; stable disease (SD) is defined as
      the persistence of the disease; and progressive disease (PD) is defined as the appearance of
      endometrial cancer in patients. Continuous therapies will be needed in PR or NR. Patients
      with PD will be recommended for hysterectomy.

      Two months of maintenance treatment will be recommended for patients with CR, and
      participants will be followed up for 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathological response rate
time frame: 12 to 16 weeks
description: From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 16 weeks.
measure: Pathological response rate
time frame: 28 to 32 weeks
description: From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 32 weeks.
measure: Pathological response duration
time frame: Up to 2 years
description: Pathological response duration
measure: Pathological response rate classified by different blood lipid level
time frame: Up to 32 weeks
description: Pathological response rate classified by different blood lipid level
measure: Toxicity evaluation
time frame: Up to 32 weeks
description: Toxicity evaluation according to CTCAE 5.0 version.
measure: Relapse rate
time frame: up to 2 years after the therapy for each patient
measure: Pregnancy rate
time frame: up to 2 years after the therapy for each patient
arm group label: MA + Rosuvastatin
arm group type: Experimental
description: Patients will receive MA 160 mg and rosuvastatin 10 mg by mouth daily for at least 6 months.Then every 3 months, hysteroscopy will be used to evaluate the endometrial condition, and findings will be recorded.
Due to personal reasons, it may not be possible to accept hysteroscopic evaluation every three months, then the longest duration will be 8 months.
intervention type: Drug
intervention name: Megestrol Acetate
description: At a dosage of 160 mg/day
arm group label: MA + Rosuvastatin
intervention type: Drug
intervention name: Rosuvastatin
description: At a dosage of 10 mg/day
arm group label: MA + Rosuvastatin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Xiaojun Chen
role: Principal Investigator
affiliation: Obstetrics and Gynecology Hospital, Fudan University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Obstetrics & Gynecology Hospital of Fudan University
investigator full name: Xiaojun Chen
investigator title: Principle investigator
mesh term: Endometrial Hyperplasia
mesh term: Hyperplasia
mesh term: Megestrol
mesh term: Megestrol Acetate
mesh term: Rosuvastatin Calcium