Improving the Treatment for Women With Early Stage Cancer of the Uterus - Full Text View

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:

MedlinePlus related topics: Benign Tumors Cancer Uterine Cancer Weight Control

Drug Information available for: Metformin Levonorgestrel Metformin hydrochloride

U.S. FDA Resources

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:

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 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 suspected histologically confirmed Endometrial Cancer only
No lymph vascular invasion on curetting or pipelle
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
No Mirena® IUD or Mirena® IUD inserted < 6 weeks prior to enrolment

Exclusion Criteria:

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
Prior treatment for EAC or EHA
Patients with a history of pelvic or abdominal radiotherapy
Unwilling to have additional endometrial biopsies or curettes or unable to attend three monthly clinical assessments
Unable to provide informed consent or 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
Breastfeeding mothers

Contacts and Locations

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:	June 2, 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
Adenocarcinoma, Mucinous
Endometrial Neoplasms
Endometrial Hyperplasia
Hyperplasia
Uterine Neoplasms
Carcinoma, Endometrioid
Adenoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
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

ClinicalTrials.gov processed this record on June 18, 2013

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