<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/NCT01686126</url>
  </required_header>
  <id_info>
    <org_study_id>feMMe</org_study_id>
    <nct_id>NCT01686126</nct_id>
  </id_info>
  <brief_title>Improving the Treatment for Women With Early Stage Cancer of the Uterus</brief_title>
  <acronym>feMMe</acronym>
  <official_title>A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queensland Centre for Gynaecological Cancer</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The University of Queensland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Queensland University of Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Queensland Centre for Gynaecological Cancer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently the standard treatment for early stage endometrial cancer or endometrial&#xD;
      hyperplasia with atypia is a total hysterectomy (an operation to remove the uterus) and&#xD;
      removal of both ovaries. While highly effective, this surgery carries significant side&#xD;
      effects for:&#xD;
&#xD;
        -  young women who still wish to have children and would lose fertility; and&#xD;
&#xD;
        -  women with one or more disorders (or diseases) in addition to the early stage&#xD;
           endometrial cancer or endometrial hyperplasia with atypia and/or morbid obesity who are&#xD;
           at risk for surgical complications making surgery unsafe.&#xD;
&#xD;
      This study will access a new approach to the treatment of endometrial cancer to spare women&#xD;
      of having to undergo major surgery that may be unwanted or unnecessary.&#xD;
&#xD;
      Mirena is approved in Australia for contraception, to treat heavy bleeding, and to prevent&#xD;
      thickening of the lining of the uterus (endometrial hyperplasia) during oestrogen replacement&#xD;
      therapy (HRT). However it is not approved to treat early stage endometrial cancer or&#xD;
      endometrial hyperplasia with atypia. This research project will test to see if Mirena is an&#xD;
      effective treatment for early stage endometrial cancer and endometrial hyperplasia with&#xD;
      atypia.&#xD;
&#xD;
      Metformin is approved in Australia to treat Diabetes. However it is not approved to treat&#xD;
      early stage endometrial cancer or endometrial hyperplasia with atypia. Therefore, it is an&#xD;
      experimental treatment for early stage endometrial cancer and endometrial hyperplasia with&#xD;
      atypia. This means that it must be tested to see if it is an effective treatment for early&#xD;
      stage endometrial cancer and endometrial hyperplasia with atypia.&#xD;
&#xD;
      Weight loss interventions are feasible and safe, and already being implemented by&#xD;
      gynaecologic oncologist to make women eligible for surgery. Weight loss of 7% body weight&#xD;
      induces a large biological effect (for example reduces incidence of diabetes by 58%, and&#xD;
      hypertension by 26%).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 2012</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">October 3, 2022</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>Pathological complete response</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Predict the response to treatment</measure>
    <time_frame>6 months</time_frame>
    <description>To predict the response to treatment through blood and tissue molecular biomarkers and to increase our molecular understanding of the biological pathogenesis of &quot;early&quot; EAC.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">165</enrollment>
  <condition>Complex Endometrial Hyperplasia With Atypia</condition>
  <condition>Grade 1 Endometrial Endometrioid Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Mirena + Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mirena</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mirena + Weight Loss Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levonorgestrel</intervention_name>
    <description>Intrauterine device</description>
    <arm_group_label>Mirena</arm_group_label>
    <arm_group_label>Mirena + Metformin</arm_group_label>
    <arm_group_label>Mirena + Weight Loss Intervention</arm_group_label>
    <other_name>Mirena</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>oral medication</description>
    <arm_group_label>Mirena + Metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Females with a BMI &gt; 30 kg/m2 wishing to retain fertility or females who are at high&#xD;
             risk of surgical complications due to co-morbidities or obesity&#xD;
&#xD;
          2. Over 18 years of age at time of randomisation&#xD;
&#xD;
          3. Histologically confirmed complex endometrial hyperplasia with atypia or grade 1&#xD;
             endometrioid endometrial adenocarcinoma on a curette or endometrial biopsy&#xD;
&#xD;
          4. CT or MRI scan of pelvis, abdomen and chest (or chest X-Ray) suggesting the absence of&#xD;
             extrauterine disease&#xD;
&#xD;
          5. Myometrial invasion on MRI of not more than 50%, for women with histologically&#xD;
             confirmed Endometrial Cancer only (for women who are unable to fit into an MRI machine&#xD;
             inclusion into trial is at investigators discretion)&#xD;
&#xD;
          6. No lymph vascular invasion on curetting or pipelle, if able to be assessed on sample&#xD;
&#xD;
          7. Serum CA125 ≤ 30 U/mL&#xD;
&#xD;
          8. No hypersensitivity or contraindications for Mirena&#xD;
&#xD;
          9. Ability to comply with endometrial biopsies at specified intervals&#xD;
&#xD;
         10. Negative serum or urine pregnancy test in pre-menopausal women and women &lt; 2 years&#xD;
             after the onset of menopause&#xD;
&#xD;
         11. Creatinine &lt; 150µmol/L (1.7 mg/dL) to be randomised into Mirena + Metformin arm (can&#xD;
             still be eligible to be randomised to Mirena only or Mirena + Weight Loss, see section&#xD;
             5.4 Other Eligibility Criteria Considerations)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. ECOG performance status &gt; 3&#xD;
&#xD;
          2. Grade 1 endometrioid adenocarcinoma of the endometrium with myometrial invasion deeper&#xD;
             than 50% on MRI or any patients with grade 2 or grade 3 endometrioid adenocarcinoma&#xD;
&#xD;
          3. Histological (cell) type other than endometrioid adenocarcinoma (sarcomas or high risk&#xD;
             endometrial e.g. papillary serous, clear cell)&#xD;
&#xD;
          4. Pregnant or planning to become pregnant during trial period&#xD;
&#xD;
          5. Has had prior treatment or undergoing current treatment for EAC or EHA&#xD;
&#xD;
          6. Patients with a history of pelvic or abdominal radiotherapy&#xD;
&#xD;
          7. Unwilling to have additional endometrial biopsies or curettes and unable to attend&#xD;
             three monthly clinical assessments&#xD;
&#xD;
          8. Unable to provide informed consent&#xD;
&#xD;
          9. Unable or unwilling to complete questionnaires&#xD;
&#xD;
         10. Evidence of extrauterine spread on medical imaging&#xD;
&#xD;
         11. Congenital or acquired uterine anomaly which distorts the uterine cavity&#xD;
&#xD;
         12. Acute pelvic inflammatory disease&#xD;
&#xD;
         13. Conditions associated with increased susceptibility to infections with microorganisms&#xD;
             (e.g., AIDS, leukaemia, IV drug abuse) according to the patients Medical History&#xD;
&#xD;
         14. Genital actinomycosis&#xD;
&#xD;
         15. Current other cancer, except low grade malignancies that do not require any systemic&#xD;
             treatment or treatment to the pelvis&#xD;
&#xD;
         16. Breastfeeding mothers&#xD;
&#xD;
         17. Mirena inserted greater than 12 weeks before randomisation/enrolment&#xD;
&#xD;
         18. Previous use of Mirena within the last 5 years from randomisation/enrolment&#xD;
&#xD;
         19. Contraindications to both Metformin and weight loss&#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>Andreas Obermair</last_name>
    <role>Study Chair</role>
    <affiliation>Queensland Centre for Gynaecological Cancer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chris O'Brien Lifehouse</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Wesley Hospital</name>
      <address>
        <city>Auchenflower</city>
        <state>Queensland</state>
        <zip>4066</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenslopes Private Hospital</name>
      <address>
        <city>Greenslopes</city>
        <state>Queensland</state>
        <zip>4120</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Health Services, Brisbane</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mater Private Hospital</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gold Coast Hospital</name>
      <address>
        <city>Southport</city>
        <state>Queensland</state>
        <zip>4215</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Townsville Hospital</name>
      <address>
        <city>Townsville</city>
        <state>Queensland</state>
        <zip>4810</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Women's Hospital</name>
      <address>
        <city>Carlton</city>
        <state>Victoria</state>
        <zip>3053</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Medical Centre</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Edward Memorial Hospital for Women</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6008</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John of God Hospital</name>
      <address>
        <city>Subiaco</city>
        <state>Western Australia</state>
        <zip>6904</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>1023</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Middlemore Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>2025</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christchurch Women's Hospital</name>
      <address>
        <city>Christchurch</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Hospital</name>
      <address>
        <city>Wellington</city>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2012</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>endometrial hyperplasia</keyword>
  <keyword>endometrial adenocarcinoma</keyword>
  <keyword>Gynecological Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Carcinoma, Endometrioid</mesh_term>
    <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>Metformin</mesh_term>
    <mesh_term>Levonorgestrel</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/NCT01686126
org study id: feMMe
nct id: NCT01686126
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Currently the standard treatment for early stage endometrial cancer or endometrial
      hyperplasia with atypia is a total hysterectomy (an operation to remove the uterus) and
      removal of both ovaries. While highly effective, this surgery carries significant side
      effects for:

        -  young women who still wish to have children and would lose fertility; and

        -  women with one or more disorders (or diseases) in addition to the early stage
           endometrial cancer or endometrial hyperplasia with atypia and/or morbid obesity who are
           at risk for surgical complications making surgery unsafe.

      This study will access a new approach to the treatment of endometrial cancer to spare women
      of having to undergo major surgery that may be unwanted or unnecessary.

      Mirena is approved in Australia for contraception, to treat heavy bleeding, and to prevent
      thickening of the lining of the uterus (endometrial hyperplasia) during oestrogen replacement
      therapy (HRT). However it is not approved to treat early stage endometrial cancer or
      endometrial hyperplasia with atypia. This research project will test to see if Mirena is an
      effective treatment for early stage endometrial cancer and endometrial hyperplasia with
      atypia.

      Metformin is approved in Australia to treat Diabetes. However it is not approved to treat
      early stage endometrial cancer or endometrial hyperplasia with atypia. Therefore, it is an
      experimental treatment for early stage endometrial cancer and endometrial hyperplasia with
      atypia. This means that it must be tested to see if it is an effective treatment for early
      stage endometrial cancer and endometrial hyperplasia with atypia.

      Weight loss interventions are feasible and safe, and already being implemented by
      gynaecologic oncologist to make women eligible for surgery. Weight loss of 7% body weight
      induces a large biological effect (for example reduces incidence of diabetes by 58%, and
      hypertension by 26%).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathological complete response
time frame: 6 months
measure: Predict the response to treatment
time frame: 6 months
description: To predict the response to treatment through blood and tissue molecular biomarkers and to increase our molecular understanding of the biological pathogenesis of "early" EAC.
arm group label: Mirena + Metformin
arm group type: Experimental
description: Metformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
arm group label: Mirena
arm group type: Experimental
description: Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
arm group label: Mirena + Weight Loss Intervention
arm group type: Experimental
description: Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers
intervention type: Drug
intervention name: Levonorgestrel
description: Intrauterine device
arm group label: Mirena
arm group label: Mirena + Metformin
arm group label: Mirena + Weight Loss Intervention
other name: Mirena
intervention type: Drug
intervention name: Metformin
description: oral medication
arm group label: Mirena + Metformin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andreas Obermair
role: Study Chair
affiliation: Queensland Centre for Gynaecological Cancer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: New Zealand
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Carcinoma, Endometrioid
mesh term: Endometrial Hyperplasia
mesh term: Hyperplasia
mesh term: Metformin
mesh term: Levonorgestrel
sharing ipd: No