1. A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss in Patients with Early Stage Cancer of the Endometrium Study Chair: Andreas Obermair Trial Manager: Fiona Menzies Trial Coordinator: Kerry Millgate

2. Background Endometrial cancer common in AUS  Becoming increasingly common in young women still desiring fertility  Becoming common in elderly patients suffering from significant medical co-morbidities (increased surgical risks)  Problem area: Super obese patients  Surgical complications high  Conversion to open surgery high  Hospital stay + Costs significant

3. Adverse events are common Morbidly obese woman EAC FIGO g1, no myoinvasion Respiratory failure secondary to pneumonia Unplanned ICU admission on day 5; Requires ventilation, imaging, i.v. ABs

4. Treatment alternative is availabale Progestins offered on case-to-case basis (Mirena ± oral progestins)

5. Study Objectives  Primary: To determine the efficacy of Mirena IUD ± Metformin ± Weight Loss to achieve a pathological complete response (pCR) in endometrial cancer at 6 months from study treatment start.  Secondary: Endometrial cancer biomarkers will be assessed at different time points to enhance our understanding of the molecular processes and to predict a treatment response.

6. Study Endpoints  Primary: Pathological Complete Response  Secondary: To predict the response to treatment through clinical, blood and tissue molecular biomarkers and to increase our molecular understanding of the biological pathogenesis of “early” EAC.

7. Schema of patient flow through study Mirena ± Metformin ± Weight Loss

8. feMME Trial - Eligibility Target: 95 ± 75 patients with complex endometrial hyperplasia with atypia or grade 1 EAC Eligibility:  Complex Endometrial Hyperplasia with atypia OR  Grade 1 EAC – avoid enrolling patients with advanced disease who need expedited surgery  Patients at high surgical risks or wish to retain fertility  BMI > 30 kg/m2  CT scan: absence of extrauterine disease  MRI: Myometrial invasion <50%  Serum CA125 ≤30 U/mL

9. Contact Andreas Obermair: obermair@powerup.com.auobermair@powerup.com.au Acknowledgements: QUT (M Janda), ANZGOG (RAC, Val Gebski) Endorsed by ANZGOG and ASGO National Ethics Application (covers NSW, VIC) QCGC will facilitate HREC applications in other states