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

Prior treatment

• Has had prior treatment or undergoing current treatment for EAC or EHA
• Mirena inserted greater than 12 weeks before randomisation/enrolment
• Previous use of Mirena within the last 5 years from randomisation/enrolment

Other illness

• Patients with a history of pelvic or abdominal radiotherapy
• 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
• Current other cancer, except low grade malignancies that do not require any systemic treatment or treatment to the pelvis

Other

• 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
• 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
• Genital actinomycosis
• Breastfeeding mothers
• Contraindications to both Metformin and weight loss

• 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)