Trial purpose
Cancer treatment
Tumor type
Gynaecological
Age
18+
Clinical summary
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%).
Conditions
This trial is treating people with Endometrial Cancer
Eligibility
Inclusion
- 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
- 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
Inclusion
- You are able to swallow medication by mouth.
- You have been diagnosed with cancer, but have not received any treatment.
- Your cancer has not spread to other parts of the body (localised).
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
Queensland Centre for Gynaecological Cancer
Scientific Title
A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium
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