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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01686126




Registration number
NCT01686126
Ethics application status
Date submitted
12/09/2012
Date registered
17/09/2012
Date last updated
28/08/2024

Titles & IDs
Public title
Improving the Treatment for Women With Early Stage Cancer of the Uterus
Scientific title
A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium
Secondary ID [1] 0 0
feMMe
Universal Trial Number (UTN)
Trial acronym
feMMe
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Complex Endometrial Hyperplasia With Atypia 0 0
Grade 1 Endometrial Endometrioid Adenocarcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Reproductive Health and Childbirth 0 0 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Levonorgestrel
Treatment: Drugs - Metformin

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

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

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


Treatment: Drugs: Levonorgestrel
Intrauterine device

Treatment: Drugs: Metformin
oral medication
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathological complete response
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Predict the response to treatment
Timepoint [1] 0 0
6 months

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
Accrual to date
Final
165
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
The Wesley Hospital - Auchenflower
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [4] 0 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [5] 0 0
Mater Health Services, Brisbane - South Brisbane
Recruitment hospital [6] 0 0
Mater Private Hospital - South Brisbane
Recruitment hospital [7] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [8] 0 0
Townsville Hospital - Townsville
Recruitment hospital [9] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 0 0
Royal Women's Hospital - Carlton
Recruitment hospital [11] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [12] 0 0
King Edward Memorial Hospital for Women - Perth
Recruitment hospital [13] 0 0
St John of God Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
4120 - Greenslopes
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
4810 - Townsville
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
3053 - Carlton
Recruitment postcode(s) [10] 0 0
3168 - Clayton
Recruitment postcode(s) [11] 0 0
6008 - Perth
Recruitment postcode(s) [12] 0 0
6904 - Subiaco
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Government body
Name
Queensland Centre for Gynaecological Cancer
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The University of Queensland
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Queensland University of Technology
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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%).
Trial website
https://clinicaltrials.gov/study/NCT01686126
Trial related presentations / 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. doi: 10.1016/j.ygyno.2021.05.016.
Public notes

Contacts
Principal investigator
Name 0 0
Andreas Obermair
Address 0 0
Queensland Centre for Gynaecological Cancer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01686126