Improving the Treatment for Women With Early Stage Cancer of the Uterus

NCT01686126 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: feMMe
• Study Type: interventional
• Target: 165
• Locations: 2 countries
• Sites: 17

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%).

Conditions

Complex Endometrial Hyperplasia With Atypia; Grade 1 Endometrial Endometrioid Adenocarcinoma

Keywords

endometrial hyperplasia; endometrial adenocarcinoma; Gynecological Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete response

  6 months

Secondary Outcomes (1)

• Predict the response to treatment

  6 months

Study Arms (3)

Mirena + Metformin

EXPERIMENTAL

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

Drug: Levonorgestrel; Drug: Metformin

Mirena

EXPERIMENTAL

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

Drug: Levonorgestrel

Mirena + Weight Loss Intervention

EXPERIMENTAL

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

Drug: Levonorgestrel

Interventions

Levonorgestrel DRUG

Intrauterine device

Also known as: Mirena

Mirena; Mirena + Metformin; Mirena + Weight Loss Intervention

Metformin DRUG

oral medication

Mirena + Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 or MRI scan of pelvis, abdomen and chest (or chest X-Ray) suggesting the absence of extrauterine disease
• No lymph vascular invasion on curetting or pipelle, if able to be assessed on sample
• 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
• 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)

You may not qualify if:

• 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
• Has had prior treatment or undergoing current treatment for EAC or EHA
• Patients with a history of pelvic or abdominal radiotherapy
• Unwilling to have additional endometrial biopsies or curettes and unable to attend three monthly clinical assessments
• Unable to provide informed consent
• Unable or unwilling to 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, except low grade malignancies that do not require any systemic treatment or treatment to the pelvis

Sponsors & Collaborators

• Queensland Centre for Gynaecological Cancer: lead
• The University of Queensland: collaborator
• Queensland University of Technology: collaborator

Study Sites (17)

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Wesley Hospital

Auchenflower, Queensland, 4066, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Greenslopes Private Hospital

Greenslopes, Queensland, 4120, Australia

Location

Mater Health Services, Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Mater Private Hospital

South Brisbane, Queensland, 4101, Australia

Location

Gold Coast Hospital

Southport, Queensland, 4215, Australia

Location

Townsville Hospital

Townsville, Queensland, 4810, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Women's Hospital

Carlton, Victoria, 3053, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

King Edward Memorial Hospital for Women

Perth, Western Australia, 6008, Australia

Location

St John of God Hospital

Subiaco, Western Australia, 6904, Australia

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Middlemore Hospital

Auckland, 2025, New Zealand

Location

Christchurch Women's Hospital

Christchurch, New Zealand

Location

Wellington Hospital

Wellington, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 33762086 DERIVED

MeSH Terms

Conditions

Endometrial Hyperplasia

Interventions

Levonorgestrel; Metformin

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Andreas Obermair

  Queensland Centre for Gynaecological Cancer

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2012
• First Posted: September 17, 2012
• Study Start: December 1, 2012
• Primary Completion: October 3, 2022
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (13); NZ (4)