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

Sponsor
Queensland Centre for Gynaecological Cancer (Other)
Overall Status
Unknown status
CT.gov ID
NCT01686126
Collaborator
The University of Queensland (Other), Queensland University of Technology (Other)
165
Enrollment
17
Locations
3
Arms
108
Anticipated Duration (Months)
9.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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%).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
165 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium
Actual Study Start Date :
Dec 1, 2012
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pathological complete response [6 months]

    Secondary Outcome Measures

    1. Predict the response to treatment [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Chris O'Brien Lifehouse Camperdown New South Wales Australia 2050
    2 The Wesley Hospital Auchenflower Queensland Australia 4066
    3 Royal Brisbane and Women's Hospital Brisbane Queensland Australia 4029
    4 Greenslopes Private Hospital Greenslopes Queensland Australia 4120
    5 Mater Health Services, Brisbane South Brisbane Queensland Australia 4101
    6 Mater Private Hospital South Brisbane Queensland Australia 4101
    7 Gold Coast Hospital Southport Queensland Australia 4215
    8 Townsville Hospital Townsville Queensland Australia 4810
    9 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    10 Royal Women's Hospital Carlton Victoria Australia 3053
    11 Monash Medical Centre Clayton Victoria Australia 3168
    12 King Edward Memorial Hospital for Women Perth Western Australia Australia 6008
    13 St John of God Hospital Subiaco Western Australia Australia 6904
    14 Auckland City Hospital Auckland New Zealand 1023
    15 Middlemore Hospital Auckland New Zealand 2025
    16 Christchurch Women's Hospital Christchurch New Zealand
    17 Wellington Hospital Wellington New Zealand

    Sponsors and Collaborators

    • Queensland Centre for Gynaecological Cancer
    • The University of Queensland
    • Queensland University of Technology

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Queensland Centre for Gynaecological Cancer
    ClinicalTrials.gov Identifier:
    NCT01686126
    Other Study ID Numbers:
    • feMMe
    First Posted:
    Sep 17, 2012
    Last Update Posted:
    Mar 10, 2021
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Queensland Centre for Gynaecological Cancer
    endometrial hyperplasia
    endometrial adenocarcinoma
    Gynecological Cancer
    Additional relevant MeSH terms:
    Adenocarcinoma
    Carcinoma, Endometrioid
    Endometrial Hyperplasia
    Hyperplasia
    Metformin
    Levonorgestrel

    Study Results

    No Results Posted as of Mar 10, 2021