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

• ClinicalTrials.gov Identifier: NCT01686126
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2012
• Last Update Posted: April 18, 2023
• Sponsor: Queensland Centre for Gynaecological Cancer
• Collaborators: The University of Queensland; Queensland University of Technology
• Information provided by (Responsible Party): Queensland Centre for Gynaecological Cancer

Tracking Information

• First Submitted Date: September 12, 2012
• First Posted Date: September 17, 2012
• Last Update Posted Date: April 18, 2023
• Actual Study Start Date: December 2012
• Actual Primary Completion Date: October 3, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 14, 2012): Pathological complete response [ Time Frame: 6 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 14, 2012)

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Improving the Treatment for Women With Early Stage Cancer of the Uterus
• Official Title: A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium

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%).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Complex Endometrial Hyperplasia With Atypia
• Grade 1 Endometrial Endometrioid Adenocarcinoma

Intervention

• Drug: Levonorgestrel
  Intrauterine device
  Other Name: Mirena
• Drug: Metformin
  oral medication

Study Arms

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

  • Drug: Levonorgestrel
  • Drug: Metformin
• Experimental: Mirena
  Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
  Intervention: Drug: Levonorgestrel
• Experimental: Mirena + Weight Loss Intervention
  Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers
  Intervention: Drug: Levonorgestrel

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 2, 2013): 165
• Original Estimated Enrollment (submitted: September 14, 2012): 111
• Estimated Study Completion Date: December 2023
• Actual Primary Completion Date: October 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, New Zealand

Administrative Information

• NCT Number: NCT01686126
• Other Study ID Numbers: feMMe
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Queensland Centre for Gynaecological Cancer
• Original Responsible Party: Same as current
• Current Study Sponsor: Queensland Centre for Gynaecological Cancer
• Original Study Sponsor: Same as current

Collaborators

• The University of Queensland
• Queensland University of Technology

Investigators

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

• PRS Account: Queensland Centre for Gynaecological Cancer
• Verification Date: April 2023