Improving the Treatment for Women With Early Stage Cancer of the Uterus (feMMe)

April 13, 2023 updated by: Queensland Centre for Gynaecological Cancer

A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium

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%).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

165

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
    • Queensland
      • Auchenflower, Queensland, Australia, 4066
        • The Wesley Hospital
      • Brisbane, Queensland, Australia, 4029
        • Royal Brisbane and Women's Hospital
      • Greenslopes, Queensland, Australia, 4120
        • Greenslopes Private Hospital
      • South Brisbane, Queensland, Australia, 4101
        • Mater Health Services, Brisbane
      • South Brisbane, Queensland, Australia, 4101
        • Mater Private Hospital
      • Southport, Queensland, Australia, 4215
        • Gold Coast Hospital
      • Townsville, Queensland, Australia, 4810
        • Townsville Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
    • Victoria
      • Carlton, Victoria, Australia, 3053
        • Royal Women's Hospital
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre
    • Western Australia
      • Perth, Western Australia, Australia, 6008
        • King Edward Memorial Hospital for Women
      • Subiaco, Western Australia, Australia, 6904
        • St John of God Hospital
  • New Zealand
      • Auckland, New Zealand, 1023
        • Auckland City Hospital
      • Auckland, New Zealand, 2025
        • Middlemore Hospital
      • Christchurch, New Zealand
        • Christchurch Women's Hospital
      • Wellington, New Zealand
        • Wellington Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Females with a BMI > 30 kg/m2 wishing to retain fertility or females who are at high risk of surgical complications due to co-morbidities or obesity
  2. Over 18 years of age at time of randomisation
  3. Histologically confirmed complex endometrial hyperplasia with atypia or grade 1 endometrioid endometrial adenocarcinoma on a curette or endometrial biopsy
  4. CT or MRI scan of pelvis, abdomen and chest (or chest X-Ray) suggesting the absence of extrauterine disease
  5. Myometrial invasion on MRI of not more than 50%, for women with histologically confirmed Endometrial Cancer only (for women who are unable to fit into an MRI machine inclusion into trial is at investigators discretion)
  6. No lymph vascular invasion on curetting or pipelle, if able to be assessed on sample
  7. Serum CA125 ≤ 30 U/mL
  8. No hypersensitivity or contraindications for Mirena
  9. Ability to comply with endometrial biopsies at specified intervals
  10. Negative serum or urine pregnancy test in pre-menopausal women and women < 2 years after the onset of menopause
  11. Creatinine < 150µmol/L (1.7 mg/dL) to be randomised into Mirena + Metformin arm (can still be eligible to be randomised to Mirena only or Mirena + Weight Loss, see section 5.4 Other Eligibility Criteria Considerations)

Exclusion Criteria:

  1. ECOG performance status > 3
  2. Grade 1 endometrioid adenocarcinoma of the endometrium with myometrial invasion deeper than 50% on MRI or any patients with grade 2 or grade 3 endometrioid adenocarcinoma
  3. Histological (cell) type other than endometrioid adenocarcinoma (sarcomas or high risk endometrial e.g. papillary serous, clear cell)
  4. Pregnant or planning to become pregnant during trial period
  5. Has had prior treatment or undergoing current treatment for EAC or EHA
  6. Patients with a history of pelvic or abdominal radiotherapy
  7. Unwilling to have additional endometrial biopsies or curettes and unable to attend three monthly clinical assessments
  8. Unable to provide informed consent
  9. Unable or unwilling to complete questionnaires
  10. Evidence of extrauterine spread on medical imaging
  11. Congenital or acquired uterine anomaly which distorts the uterine cavity
  12. Acute pelvic inflammatory disease
  13. Conditions associated with increased susceptibility to infections with microorganisms (e.g., AIDS, leukaemia, IV drug abuse) according to the patients Medical History
  14. Genital actinomycosis
  15. Current other cancer, except low grade malignancies that do not require any systemic treatment or treatment to the pelvis
  16. Breastfeeding mothers
  17. Mirena inserted greater than 12 weeks before randomisation/enrolment
  18. Previous use of Mirena within the last 5 years from randomisation/enrolment
  19. Contraindications to both Metformin and weight loss

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mirena + Metformin
Metformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Drug: Levonorgestrel
Intrauterine device
Other Names:
  • Mirena
Drug: Metformin
oral medication
Experimental: Mirena
Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Drug: Levonorgestrel
Intrauterine device
Other Names:
  • Mirena
Experimental: Mirena + Weight Loss Intervention
Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers
Drug: Levonorgestrel
Intrauterine device
Other Names:
  • Mirena

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pathological complete response
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predict the response to treatment
Time Frame: 6 months
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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queensland Centre for Gynaecological Cancer

Collaborators

The University of Queensland
Queensland University of Technology

Investigators

  • Study Chair: Andreas Obermair, Queensland Centre for Gynaecological Cancer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2012

Primary Completion (Actual)

October 3, 2022

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

September 12, 2012

First Submitted That Met QC Criteria

September 14, 2012

First Posted (Estimate)

September 17, 2012

Study Record Updates

Last Update Posted (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 13, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • feMMe

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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