<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/NCT03241888</url>
  </required_header>
  <id_info>
    <org_study_id>2017-30-1</org_study_id>
    <nct_id>NCT03241888</nct_id>
  </id_info>
  <brief_title>Megestrol Acetate Plus LNG-IUS in Young Women With Endometrial Atypical Hyperplasia</brief_title>
  <official_title>Megestrol Acetate Plus LNG-IUS to Megestrol Acetate or LNG-IUS in Young Women With Endometrial Atypical Hyperplasia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai 6th People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai Changning Maternity &amp; Infant Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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;
      or LNG-IUS alone in patients with endometrial atypical hyperplasia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After diagnosed of endometrial atypical hyperplasia (EAH) 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 3 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 LNG-IUS&#xD;
      insertion on Arm II and MA 160 mg plus LNG-IUS insertion on Arm III. Then an hysteroscope&#xD;
      will be used to evaluate the endometrial condition every 3 months, and the findings will be&#xD;
      recorded. For patients with EAH, complete response (CR) is defined as the reversion of&#xD;
      endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response&#xD;
      (PR) is defined as regression to simple or complex hyperplasia without atypia; no response&#xD;
      (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as&#xD;
      the appearance of endometrial cancer in patients. Continuous therapies will be needed in PR,&#xD;
      NR or PD.&#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>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 among each arm.</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 the therapeutic period, so that bring economic benefits.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Atypical Endometrial Hyperplasia</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>LNG-IUS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive 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>
  <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>Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.</description>
    <arm_group_label>LNG-IUS</arm_group_label>
    <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 endometrial atypical hyperplasia based upon&#xD;
             hysteroscopy&#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 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>
  <reference>
    <citation>Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. Int J Gynaecol Obstet. 2015 Dec;131(3):234-9. doi: 10.1016/j.ijgo.2015.06.031. Epub 2015 Sep 8.</citation>
    <PMID>26384790</PMID>
  </reference>
  <reference>
    <citation>Park JY, Kim DY, Kim JH, Kim YM, Kim KR, Kim YT, Seong SJ, Kim TJ, Kim JW, Kim SM, Bae DS, Nam JH. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013 Mar;49(4):868-74. doi: 10.1016/j.ejca.2012.09.017. Epub 2012 Oct 13.</citation>
    <PMID>23072814</PMID>
  </reference>
  <reference>
    <citation>Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.</citation>
    <PMID>24286192</PMID>
  </reference>
  <reference>
    <citation>Wildemeersch D, Janssens D, Pylyser K, De Wever N, Verbeeck G, Dhont M, Tjalma W. Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas. 2007 Jun 20;57(2):210-3. doi: 10.1016/j.maturitas.2006.12.004. Epub 2007 Jan 31.</citation>
    <PMID>17270370</PMID>
  </reference>
  <reference>
    <citation>Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol. 2002 Apr;186(4):651-7. doi: 10.1067/mob.2002.122130.</citation>
    <PMID>11967486</PMID>
  </reference>
  <reference>
    <citation>Chen M, Jin Y, Li Y, Bi Y, Shan Y, Pan L. Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer. Int J Gynaecol Obstet. 2016 Jan;132(1):34-8. doi: 10.1016/j.ijgo.2015.06.046. Epub 2015 Oct 1.</citation>
    <PMID>26493012</PMID>
  </reference>
  <verification_date>June 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>June 18, 2020</last_update_submitted>
  <last_update_submitted_qc>June 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 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>
  <keyword>Levonorgestrel-releasing intrauterine system</keyword>
  <keyword>megestrol acetate</keyword>
  <keyword>Atypical Endometrial Hyperplasia</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>Levonorgestrel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03241888
org study id: 2017-30-1
nct id: NCT03241888
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
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
      or LNG-IUS alone in patients with endometrial atypical hyperplasia.
After diagnosed of endometrial atypical hyperplasia (EAH) 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 3 treatment groups. Patients will receive MA (megestrol
      acetate) 160 mg by mouth daily for at least 3 months on Arm I. Patients will receive LNG-IUS
      insertion on Arm II and MA 160 mg plus LNG-IUS insertion on Arm III. Then an hysteroscope
      will be used to evaluate the endometrial condition every 3 months, and the findings will be
      recorded. For patients with EAH, 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 atypia; no response
      (NR) 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,
      NR or PD.

      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: 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 among each arm.
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 the therapeutic period, so that bring economic benefits.
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: LNG-IUS
arm group type: Active Comparator
description: Patients will receive 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.
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: Active ingredient: levonorgestrel 52mg. It is a hormone-releasing T-shaped intrauterine system.
arm group label: LNG-IUS
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
citation: Gressel GM, Parkash V, Pal L. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer. Int J Gynaecol Obstet. 2015 Dec;131(3):234-9. doi: 10.1016/j.ijgo.2015.06.031. Epub 2015 Sep 8.
PMID: 26384790
citation: Park JY, Kim DY, Kim JH, Kim YM, Kim KR, Kim YT, Seong SJ, Kim TJ, Kim JW, Kim SM, Bae DS, Nam JH. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013 Mar;49(4):868-74. doi: 10.1016/j.ejca.2012.09.017. Epub 2012 Oct 13.
PMID: 23072814
citation: Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.
PMID: 24286192
citation: Wildemeersch D, Janssens D, Pylyser K, De Wever N, Verbeeck G, Dhont M, Tjalma W. Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas. 2007 Jun 20;57(2):210-3. doi: 10.1016/j.maturitas.2006.12.004. Epub 2007 Jan 31.
PMID: 17270370
citation: Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol. 2002 Apr;186(4):651-7. doi: 10.1067/mob.2002.122130.
PMID: 11967486
citation: Chen M, Jin Y, Li Y, Bi Y, Shan Y, Pan L. Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer. Int J Gynaecol Obstet. 2016 Jan;132(1):34-8. doi: 10.1016/j.ijgo.2015.06.046. Epub 2015 Oct 1.
PMID: 26493012
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 Hyperplasia
mesh term: Hyperplasia
mesh term: Megestrol
mesh term: Megestrol Acetate
mesh term: Levonorgestrel
sharing ipd: Undecided