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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Queensland Centre for Gynaecological Cancer
Sponsor:
Collaborators:
The University of Queensland
Queensland University of Technology
Information provided by (Responsible Party):
Queensland Centre for Gynaecological Cancer
ClinicalTrials.gov Identifier:
NCT01686126
First received: September 12, 2012
Last updated: March 28, 2016
Last verified: March 2016
  Purpose

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%).


Condition Intervention Phase
Complex Endometrial Hyperplasia With Atypia
Grade 1 Endometrial Endometrioid Adenocarcinoma
Drug: Levonorgestrel
Drug: Metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium

Resource links provided by NLM:


Further study details as provided by Queensland Centre for Gynaecological Cancer:

Primary Outcome Measures:
  • Pathological complete response [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Predict the response to treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 165
Study Start Date: October 2012
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mirena + Metformin
Metformin tablets, 500mg twice daily orally, 6 months Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Drug: Levonorgestrel
Intrauterine device
Other Name: Mirena
Drug: Metformin
oral medication
Experimental: Mirena
Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Drug: Levonorgestrel
Intrauterine device
Other Name: Mirena
Experimental: Mirena + Weight Loss Intervention
Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months Weight Loss Intervention will be delivered via Weight Watchers
Drug: Levonorgestrel
Intrauterine device
Other Name: Mirena

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 6 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01686126

Contacts
Contact: Vanessa L Taylor +61 7 3646 2141 vanessa.taylor3@health.qld.gov.au
Contact: Trudi Cattley, BSc +61 7 3646 0447 trudi.cattley@health.qld.gov.au

Locations
Australia, New South Wales
Chris O'Brien Lifehouse Recruiting
Camperdown, New South Wales, Australia, 2050
Principal Investigator: Jonathan Carter         
Sub-Investigator: Selvan Pather         
John Hunter Hospital Not yet recruiting
New Lambton, New South Wales, Australia, 2305
Principal Investigator: Geoffrey Otton         
Australia, Queensland
The Wesley Hospital Recruiting
Auchenflower, Queensland, Australia, 4066
Principal Investigator: Jim Nicklin         
Sub-Investigator: Andrea Garrett         
Brisbane Private Hospital Withdrawn
Brisbane, Queensland, Australia, 4000
Royal Brisbane and Women's Hospital Recruiting
Brisbane, Queensland, Australia, 4029
Principal Investigator: Andreas Obermair         
Sub-Investigator: James Nicklin         
Sub-Investigator: Russell Land         
Sub-Investigator: Andrea Garrett         
Greenslopes Private Hospital Recruiting
Greenslopes, Queensland, Australia, 4120
Principal Investigator: Andreas Obermair         
Sub-Investigator: Russell Land         
Sub-Investigator: Naven Chetty         
Mater Health Services, Brisbane Recruiting
South Brisbane, Queensland, Australia, 4101
Principal Investigator: Lewis Perrin         
Sub-Investigator: Naven Chetty         
Sub-Investigator: Alex Crandon         
Mater Private Hospital Recruiting
South Brisbane, Queensland, Australia, 4101
Principal Investigator: Lewis Perrin         
Sub-Investigator: Naven Chetty         
Gold Coast Hospital Recruiting
Southport, Queensland, Australia, 4215
Principal Investigator: Marcelo Nascimento         
Townsville Hospital Recruiting
Townsville, Queensland, Australia, 4810
Principal Investigator: Andreas Obermair         
Sub-Investigator: James Nicklin         
Sub-Investigator: Lewis Perrin         
Sub-Investigator: Russell Land         
Sub-Investigator: Andrea Garrett         
Sub-Investigator: Naven Chetty         
John Flynn Hospital Not yet recruiting
Tugun, Queensland, Australia, 4224
Principal Investigator: Marcelo Nascimento         
Sub-Investigator: Alex Crandon         
Australia, South Australia
Royal Adelaide Hospital Not yet recruiting
Adelaide, South Australia, Australia, 5000
Principal Investigator: Martin Oehler         
Queen Elizabeth Hospital Not yet recruiting
Woodville, South Australia, Australia, 5011
Principal Investigator: John Miller         
Australia, Victoria
Royal Women's Hospital Recruiting
Carlton, Victoria, Australia, 3053
Principal Investigator: Orla McNally         
Sub-Investigator: Michael Quinn         
Sub-Investigator: Deborah Neesham         
Sub-Investigator: David Wrede         
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Contact: Nicole Fairweather       nicole.fairweather@epworth.org.au   
Principal Investigator: Kym Reid         
Australia, Western Australia
King Edward Memorial Hospital for Women Recruiting
Perth, Western Australia, Australia, 6008
Principal Investigator: Yee Leung         
Sub-Investigator: Stuart Salfinger         
Sub-Investigator: Jason Tan         
St John of God Hospital Recruiting
Subiaco, Western Australia, Australia, 6904
Principal Investigator: Stuart Salfinger         
Sub-Investigator: Jason Tan         
New Zealand
Christchurch Women's Hospital Recruiting
Christchurch, New Zealand
Contact: Dianne Harker       dianne.harker@otago.ac.nz   
Principal Investigator: Peter Sykes         
Sub-Investigator: Bryony Simcock         
Wellington Hospital Recruiting
Wellington, New Zealand
Contact: Cecile Bergzoll       cecile.bergzoll@ccdhb.org.nz   
Principal Investigator: Cecile Bergzoll         
Sponsors and Collaborators
Queensland Centre for Gynaecological Cancer
The University of Queensland
Queensland University of Technology
Investigators
Study Chair: Andreas Obermair Queensland Centre for Gynaecological Cancer
  More Information

Responsible Party: Queensland Centre for Gynaecological Cancer
ClinicalTrials.gov Identifier: NCT01686126     History of Changes
Other Study ID Numbers: feMMe 
Study First Received: September 12, 2012
Last Updated: March 28, 2016
Health Authority: Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Queensland Centre for Gynaecological Cancer:
endometrial hyperplasia
endometrial adenocarcinoma
Gynecological Cancer

Additional relevant MeSH terms:
Adenocarcinoma
Hyperplasia
Carcinoma, Endometrioid
Endometrial Hyperplasia
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pathologic Processes
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Ovarian Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Uterine Diseases
Metformin
Levonorgestrel
Hypoglycemic Agents
Physiological Effects of Drugs
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral

ClinicalTrials.gov processed this record on July 24, 2016