Improving the Treatment for Women With Early Stage Cancer of the Uterus
Overview[ - collapse ][ - ]
| 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 | Complex Endometrial Hyperplasia With Atypia Grade 1 Endometrial Endometrioid Adenocarcinoma |
| Intervention | Drug: Levonorgestrel Drug: Metformin |
| Phase | Phase 2 |
| Sponsor | Queensland Centre for Gynaecological Cancer |
| 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 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 12, 2012 |
|---|---|
| Last Updated Date | August 18, 2013 |
| Start Date | October 2012 |
| Estimated Primary Completion Date | September 2015 |
| Current Primary Outcome Measures | Pathological complete response [Time Frame: 6 months] [Designated as safety issue: No] |
| Current 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. |
Descriptive Information[ + expand ][ + ]
| Brief Title | Improving the Treatment for Women With Early Stage Cancer of the Uterus |
|---|---|
| Official Title | A Phase II Randomised Clinical Trial of Mirena® ± Metformin ± Weight Loss Intervention in Patients With Early Stage Cancer of the Endometrium |
| 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%). |
| Detailed Description | Not Provided |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
|
| Intervention | Drug: Levonorgestrel Other Names: MirenaDrug: Metformin |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Enrolling by invitation |
|---|---|
| Estimated Enrollment | 165 |
| Estimated Completion Date | September 2015 |
| Estimated Primary Completion Date | September 2015 |
| Eligibility 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 |
| Gender | Female |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | Australia |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01686126 |
|---|---|
| Other Study ID Numbers | feMMe |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Queensland Centre for Gynaecological Cancer |
| Study Sponsor | Queensland Centre for Gynaecological Cancer |
| Collaborators | The University of Queensland Queensland University of Technology |
| Investigators | Study Chair: Andreas Obermair Queensland Centre for Gynaecological Cancer |
| Verification Date | August 2013 |
Locations[ + expand ][ + ]
| 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 |
| 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 |
| 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 |
| Royal Women's Hospital | Carlton, Victoria, Australia, 3053 |
| 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 |