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

Primary Purpose

Complex Endometrial Hyperplasia With Atypia, Grade 1 Endometrial Endometrioid Adenocarcinoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Levonorgestrel
Metformin
Sponsored by
Queensland Centre for Gynaecological Cancer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Complex Endometrial Hyperplasia With Atypia focused on measuring endometrial hyperplasia, endometrial adenocarcinoma, Gynecological Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Chris O'Brien Lifehouse
  • The Wesley Hospital
  • Royal Brisbane and Women's Hospital
  • Greenslopes Private Hospital
  • Mater Health Services, Brisbane
  • Mater Private Hospital
  • Gold Coast Hospital
  • Townsville Hospital
  • Royal Adelaide Hospital
  • Royal Women's Hospital
  • Monash Medical Centre
  • King Edward Memorial Hospital for Women
  • St John of God Hospital
  • Auckland City Hospital
  • Middlemore Hospital
  • Christchurch Women's Hospital
  • Wellington Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Mirena + Metformin

Mirena

Mirena + Weight Loss Intervention

Arm Description

Metformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months

Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months

Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers

Outcomes

Primary Outcome Measures

Pathological complete response

Secondary Outcome Measures

Predict the response to treatment
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.

Full Information

First Posted
September 12, 2012
Last Updated
April 13, 2023
Sponsor
Queensland Centre for Gynaecological Cancer
Collaborators
The University of Queensland, Queensland University of Technology
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1. Study Identification

Unique Protocol Identification Number
NCT01686126
Brief Title
Improving the Treatment for Women With Early Stage Cancer of the Uterus
Acronym
feMMe
Official Title
A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2012 (Actual)
Primary Completion Date
October 3, 2022 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Queensland Centre for Gynaecological Cancer
Collaborators
The University of Queensland, Queensland University of Technology

4. Oversight

Data Monitoring Committee
Yes

5. 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%).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complex Endometrial Hyperplasia With Atypia, Grade 1 Endometrial Endometrioid Adenocarcinoma
Keywords
endometrial hyperplasia, endometrial adenocarcinoma, Gynecological Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
165 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mirena + Metformin
Arm Type
Experimental
Arm Description
Metformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Arm Title
Mirena
Arm Type
Experimental
Arm Description
Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Arm Title
Mirena + Weight Loss Intervention
Arm Type
Experimental
Arm Description
Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers
Intervention Type
Drug
Intervention Name(s)
Levonorgestrel
Other Intervention Name(s)
Mirena
Intervention Description
Intrauterine device
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
oral medication
Primary Outcome Measure Information:
Title
Pathological complete response
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Predict the response to treatment
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.
Time Frame
6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Over 18 years of age at time of randomisation Histologically confirmed complex endometrial hyperplasia with atypia or grade 1 endometrioid endometrial adenocarcinoma on a curette or endometrial biopsy CT or MRI scan of pelvis, abdomen and chest (or chest X-Ray) suggesting the absence of extrauterine disease 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) No lymph vascular invasion on curetting or pipelle, if able to be assessed on sample Serum CA125 ≤ 30 U/mL No hypersensitivity or contraindications for Mirena Ability to comply with endometrial biopsies at specified intervals Negative serum or urine pregnancy test in pre-menopausal women and women < 2 years after the onset of menopause 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: ECOG performance status > 3 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 Histological (cell) type other than endometrioid adenocarcinoma (sarcomas or high risk endometrial e.g. papillary serous, clear cell) Pregnant or planning to become pregnant during trial period Has had prior treatment or undergoing current treatment for EAC or EHA Patients with a history of pelvic or abdominal radiotherapy Unwilling to have additional endometrial biopsies or curettes and unable to attend three monthly clinical assessments Unable to provide informed consent Unable or unwilling to complete questionnaires Evidence of extrauterine spread on medical imaging Congenital or acquired uterine anomaly which distorts the uterine cavity Acute pelvic inflammatory disease Conditions associated with increased susceptibility to infections with microorganisms (e.g., AIDS, leukaemia, IV drug abuse) according to the patients Medical History Genital actinomycosis Current other cancer, except low grade malignancies that do not require any systemic treatment or treatment to the pelvis Breastfeeding mothers Mirena inserted greater than 12 weeks before randomisation/enrolment Previous use of Mirena within the last 5 years from randomisation/enrolment Contraindications to both Metformin and weight loss
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Obermair
Organizational Affiliation
Queensland Centre for Gynaecological Cancer
Official's Role
Study Chair
Facility Information:
Facility Name
Chris O'Brien Lifehouse
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
The Wesley Hospital
City
Auchenflower
State/Province
Queensland
ZIP/Postal Code
4066
Country
Australia
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Greenslopes Private Hospital
City
Greenslopes
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
Facility Name
Mater Health Services, Brisbane
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Mater Private Hospital
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Gold Coast Hospital
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Facility Name
Townsville Hospital
City
Townsville
State/Province
Queensland
ZIP/Postal Code
4810
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Royal Women's Hospital
City
Carlton
State/Province
Victoria
ZIP/Postal Code
3053
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
King Edward Memorial Hospital for Women
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
St John of God Hospital
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6904
Country
Australia
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Middlemore Hospital
City
Auckland
ZIP/Postal Code
2025
Country
New Zealand
Facility Name
Christchurch Women's Hospital
City
Christchurch
Country
New Zealand
Facility Name
Wellington Hospital
City
Wellington
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33762086
Citation
Janda M, Robledo KP, Gebski V, Armes JE, Alizart M, Cummings M, Chen C, Leung Y, Sykes P, McNally O, Oehler MK, Walker G, Garrett A, Tang A, Land R, Nicklin JL, Chetty N, Perrin LC, Hoet G, Sowden K, Eva L, Tristram A, Obermair A. Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial. Gynecol Oncol. 2021 Apr;161(1):143-151. doi: 10.1016/j.ygyno.2021.01.029. Erratum In: Gynecol Oncol. 2021 Aug;162(2):526.
Results Reference
derived

Learn more about this trial

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

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