<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/NCT02990728</url>
  </required_header>
  <id_info>
    <org_study_id>CTC-184</org_study_id>
    <nct_id>NCT02990728</nct_id>
  </id_info>
  <brief_title>Mirena® ± Metformin as Fertility-preserving Treatment for Young Asian Women With Early Endometrial Cancer</brief_title>
  <official_title>Mirena® ± Metformin as Fertility-preserving Treatment for Young Asian Women With Early Endometrial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary objective To discover the efficacies of levonorgestrel-containing intrauterine device&#xD;
      (LNG-IUS, Mirena®), with or without metformin, as fertility-preserving treatment for grade 1&#xD;
      endometrioid adenocarcinoma of endometrium, cT1aN0M0 with presumed no myometrial invasion on&#xD;
      image study (MRI preferred).&#xD;
&#xD;
      Secondary objectives&#xD;
&#xD;
        1. To discover the morphological and molecular change in the endometrium tumor before and&#xD;
           after treatment&#xD;
&#xD;
        2. To discover the effectiveness of adding oral progestin to subjects who show no good&#xD;
           response to assigned&#xD;
&#xD;
        3. To compare (1) the systemic effects, including body weight change, neuropsychiatric&#xD;
           alternation, GI disturbance, skin disorder, change in serum metabolic and hepatic&#xD;
           markers between the two study patient groups; (2) The rate of long-term success defined&#xD;
           as (a) sustained remission of &gt;= 12 months starts from the histologic documentation of&#xD;
           complete remission (b) rate of pregnancy and (c) alive baby delivery, based on&#xD;
           time-to-event analysis.&#xD;
&#xD;
        4. Molecular markers and their expression before, during and after treatment, including&#xD;
           progesterone B receptor, progesterone A receptor, estrogen receptor, Ki67, PTEN and its&#xD;
           related markers, Bcl2 and its related markers and other developing markers. This is to&#xD;
           discover prediction markers to medical treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date>March 2016</start_date>
  <completion_date type="Anticipated">March 2020</completion_date>
  <primary_completion_date type="Anticipated">March 2018</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the efficacies of levonorgestrel-containing intrauterine device (LNG-IUS, Mirena®), with or without metformin</measure>
    <time_frame>the efficacies of levonorgestrel-containing intrauterine device (LNG-IUS, Mirena®), with or without metformin about 6 month</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>Mirena® + metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mirena®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant</description>
    <arm_group_label>Mirena® + metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Mirena®</intervention_name>
    <arm_group_label>Mirena®</arm_group_label>
    <arm_group_label>Mirena® + metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women &lt;= 40 years old with histologic confirmed grade 1 endometrioid adenocarcinoma of&#xD;
             the endometrium&#xD;
&#xD;
          2. Tumour is confirmed to the endometrial cavity with no evidence of metastasis on MRI&#xD;
             and/or trans-vaginal ultrasonography&#xD;
&#xD;
          3. ECOG 0-1, adequate organ function, with fertility preserving need&#xD;
&#xD;
          4. Immunohistochemical study showed positive progesterone receptor and positive estrogen&#xD;
             receptor in the endometrial tumour tissue&#xD;
&#xD;
          5. Serum CA 125 titre is within normal limit&#xD;
&#xD;
          6. Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women age &gt; 40 years or endometrial cancer other than grade 1 endometrioid&#xD;
             adenocarcinoma&#xD;
&#xD;
          2. Suspected lymph node metastasis or other metastasis appears in image study&#xD;
&#xD;
          3. Ovarian tumour in image study&#xD;
&#xD;
          4. Blurred junction between the endometrium and the myometrium on image study, with the&#xD;
             impression that myometrial invasion of the endometrial tumour cannot be ruled out&#xD;
&#xD;
          5. Ultrasonographic study or MRI show obvious adenomyosis or ovarian endometriosis&#xD;
&#xD;
          6. Women who are contraindicated to receive study treatment because of intolerance to&#xD;
             treatment agents, medical co-morbidity or other reason(s)&#xD;
&#xD;
          7. Women with history of or concurrent with malignancy other than skin basal cell&#xD;
             carcinoma&#xD;
&#xD;
          8. Women who cannot participate regular follow-up&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>December 8, 2016</last_update_submitted>
  <last_update_submitted_qc>December 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 13, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Ting-Chang Chang</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>Endometrial Cancer.Mirena®</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT02990728
org study id: CTC-184
nct id: NCT02990728
lead sponsor: 
has dmc: Yes
Primary objective To discover the efficacies of levonorgestrel-containing intrauterine device
      (LNG-IUS, Mirena®), with or without metformin, as fertility-preserving treatment for grade 1
      endometrioid adenocarcinoma of endometrium, cT1aN0M0 with presumed no myometrial invasion on
      image study (MRI preferred).

      Secondary objectives

        1. To discover the morphological and molecular change in the endometrium tumor before and
           after treatment

        2. To discover the effectiveness of adding oral progestin to subjects who show no good
           response to assigned

        3. To compare (1) the systemic effects, including body weight change, neuropsychiatric
           alternation, GI disturbance, skin disorder, change in serum metabolic and hepatic
           markers between the two study patient groups; (2) The rate of long-term success defined
           as (a) sustained remission of >= 12 months starts from the histologic documentation of
           complete remission (b) rate of pregnancy and (c) alive baby delivery, based on
           time-to-event analysis.

        4. Molecular markers and their expression before, during and after treatment, including
           progesterone B receptor, progesterone A receptor, estrogen receptor, Ki67, PTEN and its
           related markers, Bcl2 and its related markers and other developing markers. This is to
           discover prediction markers to medical treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the efficacies of levonorgestrel-containing intrauterine device (LNG-IUS, Mirena®), with or without metformin
time frame: the efficacies of levonorgestrel-containing intrauterine device (LNG-IUS, Mirena®), with or without metformin about 6 month
arm group label: Mirena® + metformin
arm group type: Experimental
description: The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant
arm group label: Mirena®
arm group type: Active Comparator
description: The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant
intervention type: Drug
intervention name: Metformin
description: The enrolled patient is allocated to either LNG-IUS only or LNG-IUS + metformin by central randomization with study site allocation. A 90-100 days of continuous treatment before first histologic assessment of treatment response is required. The patient will receive endometrial curettage or hysteroscopic evaluation and resection of suspected lesion after 90-100 days of treatment. Patients with good response to assigned treatment will continue the treatment for another 90-100 days and second histologic assessment will be performed. Patients with poor response to assigned treatment at first assessment will receive additive oral progestin therapy, along with the assigned regimen(s) as, Oral progestin, either medroxyprogesterone acetate 500 mg daily or oral megestrol acetate 160 mg daily After a total of at least 6 months treatment period, the patient with good response at first assessment is suggested to keep the Mirena for maintenance until plan to get pregnant
arm group label: Mirena® + metformin
intervention type: Device
intervention name: Mirena®
arm group label: Mirena®
arm group label: Mirena® + metformin
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Chang Gung Memorial Hospital
investigator full name: Ting-Chang Chang
investigator title: Director
mesh term: Endometrial Neoplasms
mesh term: Metformin
sharing ipd: No