<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/NCT03241914</url>
  </required_header>
  <id_info>
    <org_study_id>2017-30-2</org_study_id>
    <nct_id>NCT03241914</nct_id>
  </id_info>
  <brief_title>Megestrol Acetate Plus LNG-IUS in Young Women With Early Endometrial Cancer</brief_title>
  <official_title>Megestrol Acetate Plus LNG-IUS to Megestrol Acetate in Young Women With Early Endometrial Cancer</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 Levonorgestrel-releasing intrauterine system (LNG-IUS) will&#xD;
      not be inferior to returning the endometrial tissue to a normal state than megestrol acetate&#xD;
      alone in patients with early endometrial cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After diagnosed of endometrioid endometrial cancer (EEC) by hysteroscopy, patients will be&#xD;
      enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood&#xD;
      pressure, serum lipid level and side effects will be collected. Blood tests, including&#xD;
      fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FINS), SHBG,&#xD;
      sex hormone levels, blood lipids and anti-müllerian hormone(AMH) will be performed before&#xD;
      treatment to evacuate their metabolic conditions.&#xD;
&#xD;
      Patients are randomized to 1 of 2 treatment groups. Patients will receive MA (megestrol&#xD;
      acetate) 160 mg by mouth daily for at least 3 months on Arm I. Patients will receive MA 160&#xD;
      mg plus LNG-IUS insertion for at least 3 months on Arm II. Then an hysteroscope will be used&#xD;
      to evaluate the endometrial condition every 3 months, and the findings will be recorded. For&#xD;
      patients with EEC, complete response (CR) is defined as the reversion of endometrial disease&#xD;
      to proliferative or secretory endometrium; partial response (PR) is defined as regression to&#xD;
      simple or complex hyperplasia without atypic or atypical hyperplasia; no response (NR) is&#xD;
      defined as the persistence of the disease; and progressive disease (PD) is defined as the&#xD;
      progression of endometrial lesions. Continuous therapies will be needed in PR, NR or PD.&#xD;
&#xD;
      As the reason of the low response rate of LNG-IUS alone in EC patients (nearly 50%), and the&#xD;
      potential limitation of LNG-IUS to focal cancer lesion in endometrial cavity, the&#xD;
      investigators did not add LNG-IUS alone as a single control group.&#xD;
&#xD;
      After completion of study treatment, 2 months of maintenance treatment will be recommended&#xD;
      for patients with CR, and participants will be followed up for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 4, 2017</start_date>
  <completion_date type="Actual">June 18, 2020</completion_date>
  <primary_completion_date type="Actual">June 18, 2020</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathological response rate</measure>
    <time_frame>From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pathological response time</measure>
    <time_frame>From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months</time_frame>
    <description>median time of histologic regression from endometrial atypical hyperplasia to benign endometrium</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>up to 2 years after the treatment for each patient</time_frame>
    <description>Common side effects from these drugs include weight gain, vaginal spotting and descent of sexuality. Severe side effects include thrombus and diseases related. The investigators will record any mental or body symptoms and evaluate the correlation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of relapse</measure>
    <time_frame>up to 2 years after the treatment for each patient</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of pregnancy</measure>
    <time_frame>up to 2 years after the treatment for each patient</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance</measure>
    <time_frame>up to 2 years after the treatment for each patient</time_frame>
    <description>The investigators designed a questionnaire to evaluate the compliance through treatment as side effects of oral megestrol acetate may be more common than LNG-IUS. Self Efficacy, physical activity and social support will be scored (1 to 5) and compared between different arms.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Economic consequences through study completion</measure>
    <time_frame>From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months</time_frame>
    <description>The investigators will evaluate whether the combination could shorten therapeutic period, so that bring economic benefits to the patients.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Endometrial Neoplasm Malignant Stage I</condition>
  <arm_group>
    <arm_group_label>MA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive megestrol acetate 160 mg by mouth daily for at least 3 months.Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MA+LNG-IUS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive MA (160mg po qd) plus LNG- IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.</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</arm_group_label>
    <arm_group_label>MA+LNG-IUS</arm_group_label>
    <other_name>Megace</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Levonorgestrel-releasing Intrauterine System(LNG-IUS)</intervention_name>
    <description>levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.</description>
    <arm_group_label>MA+LNG-IUS</arm_group_label>
    <other_name>Mirena Intrauterine Device</other_name>
    <other_name>Mirena</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primarily have a confirmed diagnosis of endometrioid endometrial cancer based upon&#xD;
             hysteroscopy&#xD;
&#xD;
          -  MRI parameters shows there's no myometrial invasion, extension beyond corpus, or&#xD;
             enlarged lymph nodes&#xD;
&#xD;
          -  Have a desire for remaining reproductive function or uterus&#xD;
&#xD;
          -  Need to be able to undergo correlative treatment and follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute liver disease or liver tumor (benign or malignant) or renal dysfunction&#xD;
&#xD;
          -  Pregnancy or suspicion of pregnancy&#xD;
&#xD;
          -  Have a history of EAH or EC and have disease relapse during Merina insertion&#xD;
&#xD;
          -  Under treatment of high-dose progestin therapy more than 3 months in recent 6 months&#xD;
&#xD;
          -  Congenital or acquired uterine anomaly including fibroids if they distort the uterine&#xD;
             cavity&#xD;
&#xD;
          -  Confirmed diagnosis of malignant tumor in genital system&#xD;
&#xD;
          -  Acute severe disease such as stroke or heart infarction or a history of thrombosis&#xD;
             disease&#xD;
&#xD;
          -  Hypersensitivity or contradiction to any component of this product&#xD;
&#xD;
          -  Ask for removal of the uterus or other conservative treatment&#xD;
&#xD;
          -  Smoker(&gt;15 cigarettes 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>
  <location>
    <facility>
      <name>Obstetrics and Gynecology Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>August 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>November 19, 2020</last_update_submitted>
  <last_update_submitted_qc>November 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 20, 2020</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>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Neoplasms</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>Levonorgestrel</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/NCT03241914
org study id: 2017-30-2
nct id: NCT03241914
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
To see if megestrol acetate plus Levonorgestrel-releasing intrauterine system (LNG-IUS) will
      not be inferior to returning the endometrial tissue to a normal state than megestrol acetate
      alone in patients with early endometrial cancer.
After diagnosed of endometrioid endometrial cancer (EEC) by hysteroscopy, patients will be
      enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood
      pressure, serum lipid level and side effects will be collected. Blood tests, including
      fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting insulin (FINS), SHBG,
      sex hormone levels, blood lipids and anti-müllerian hormone(AMH) will be performed before
      treatment to evacuate their metabolic conditions.

      Patients are randomized to 1 of 2 treatment groups. Patients will receive MA (megestrol
      acetate) 160 mg by mouth daily for at least 3 months on Arm I. Patients will receive MA 160
      mg plus LNG-IUS insertion for at least 3 months on Arm II. Then an hysteroscope will be used
      to evaluate the endometrial condition every 3 months, and the findings will be recorded. For
      patients with EEC, complete response (CR) is defined as the reversion of endometrial disease
      to proliferative or secretory endometrium; partial response (PR) is defined as regression to
      simple or complex hyperplasia without atypic or atypical hyperplasia; no response (NR) is
      defined as the persistence of the disease; and progressive disease (PD) is defined as the
      progression of endometrial lesions. Continuous therapies will be needed in PR, NR or PD.

      As the reason of the low response rate of LNG-IUS alone in EC patients (nearly 50%), and the
      potential limitation of LNG-IUS to focal cancer lesion in endometrial cavity, the
      investigators did not add LNG-IUS alone as a single control group.

      After completion of study treatment, 2 months of maintenance treatment will be recommended
      for patients with CR, and participants will be followed up for 2 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Pathological response rate
time frame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
measure: Pathological response time
time frame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
description: median time of histologic regression from endometrial atypical hyperplasia to benign endometrium
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: up to 2 years after the treatment for each patient
description: Common side effects from these drugs include weight gain, vaginal spotting and descent of sexuality. Severe side effects include thrombus and diseases related. The investigators will record any mental or body symptoms and evaluate the correlation.
measure: Rate of relapse
time frame: up to 2 years after the treatment for each patient
measure: Rate of pregnancy
time frame: up to 2 years after the treatment for each patient
measure: Compliance
time frame: up to 2 years after the treatment for each patient
description: The investigators designed a questionnaire to evaluate the compliance through treatment as side effects of oral megestrol acetate may be more common than LNG-IUS. Self Efficacy, physical activity and social support will be scored (1 to 5) and compared between different arms.
measure: Economic consequences through study completion
time frame: From date of randomization until the date of CR or date of hysterectomy, whichever came first, assessed up to 12 months
description: The investigators will evaluate whether the combination could shorten therapeutic period, so that bring economic benefits to the patients.
arm group label: MA
arm group type: Active Comparator
description: Patients will receive megestrol acetate 160 mg by mouth daily for at least 3 months.Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.
arm group label: MA+LNG-IUS
arm group type: Experimental
description: Patients will receive MA (160mg po qd) plus LNG- IUS insertion for at least 3 months. Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.
intervention type: Drug
intervention name: Megestrol Acetate
description: At a dosage of 160 mg/day
arm group label: MA
arm group label: MA+LNG-IUS
other name: Megace
intervention type: Device
intervention name: Levonorgestrel-releasing Intrauterine System(LNG-IUS)
description: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.
arm group label: MA+LNG-IUS
other name: Mirena Intrauterine Device
other name: Mirena
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Obstetrics & Gynecology Hospital of Fudan University
investigator full name: Xiaojun Chen
investigator title: Principal Investigator
mesh term: Endometrial Neoplasms
mesh term: Neoplasms
mesh term: Megestrol
mesh term: Megestrol Acetate
mesh term: Levonorgestrel