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

This study is enrolling participants by invitation only.
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: August 18, 2013
Last verified: August 2013
  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: September 2015
Estimated Primary Completion Date: September 2015 (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
Other Name: Mirena
Drug: Metformin
Experimental: Mirena
Levonorgestrel (Mirena®) 52mg Intrauterine drug delivery system, 6 months
Drug: Levonorgestrel
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
Other Name: Mirena

  Eligibility

Ages Eligible for Study:   18 Years and older
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 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 suspected histologically confirmed Endometrial Cancer only
  6. No lymph vascular invasion on curetting or pipelle
  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. No Mirena® IUD or Mirena® IUD inserted < 6 weeks prior to enrolment

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. Prior treatment for EAC or EHA
  6. Patients with a history of pelvic or abdominal radiotherapy
  7. Unwilling to have additional endometrial biopsies or curettes or unable to attend three monthly clinical assessments
  8. Unable to provide informed consent or complete questionnaires
  9. Evidence of extrauterine spread on medical imaging
  10. Congenital or acquired uterine anomaly which distorts the uterine cavity
  11. Acute pelvic inflammatory disease
  12. Conditions associated with increased susceptibility to infections with microorganisms (e.g., AIDS, leukaemia, IV drug abuse) according to the patients Medical History
  13. Genital actinomycosis
  14. Current other cancer
  15. Breastfeeding mothers
  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

Locations
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
John Hunter Hospital
New Lambton, New South Wales, Australia, 2305
Newcastle Private Hospital
New Lambton Heights, New South Wales, Australia, 2305
Australia, Queensland
The Wesley Hospital
Auchenflower, Queensland, Australia, 4066
Pindarra Hospital
Benowa, Queensland, Australia, 4217
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
Brisbane Private Hospital
Brisbane, Queensland, Australia, 4000
Greenslopes Private Hospital
Greenslopes, Queensland, Australia, 4120
Mater Adult Public Hospital
South Brisbane, Queensland, Australia, 4101
Mater Private Hospital
South Brisbane, Queensland, Australia, 4101
Gold Coast Hospital
Southport, Queensland, Australia, 4215
Lake Kawana Private Hospital
Sunshine Coast, Queensland, Australia, 4574
Mater Misericordiae Hospital Townsville
Townsville, Queensland, Australia, 4810
John Flynn Hospital
Tugun, Queensland, Australia, 4224
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Calvary Health Care North Adelaide
North Adelaide, South Australia, Australia, 5006
Queen Elizabeth Hospital
Woodville, South Australia, Australia, 5011
Australia, Victoria
Royal Women's Hospital
Carlton, Victoria, Australia, 3053
Australia, Western Australia
Hollywood Private Hospital
Nedlands, Western Australia, Australia, 6009
King Edward Memorial Hospital for Women
Perth, Western Australia, Australia, 6008
St John of God Hospital
Subiaco, Western Australia, Australia, 6904
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

No publications provided

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: August 18, 2013
Health Authority: Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council

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

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

ClinicalTrials.gov processed this record on July 29, 2014