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

NCT ID: NCT01686126

Last Updated: 2024-08-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 165 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2026-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mirena + Metformin

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

Group Type: EXPERIMENTAL

Levonorgestrel

Intervention Type: DRUG

Intrauterine device

Metformin

Intervention Type: DRUG

oral medication

Mirena

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

Group Type: EXPERIMENTAL

Levonorgestrel

Intervention Type: DRUG

Intrauterine device

Mirena + Weight Loss Intervention

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

Group Type: EXPERIMENTAL

Levonorgestrel

Intervention Type: DRUG

Intrauterine device

Interventions

Levonorgestrel

Intrauterine device

Intervention Type: DRUG

Metformin

oral medication

Intervention Type: DRUG

Other Intervention Names

Mirena

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 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 12 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The University of Queensland

OTHER

Sponsor Role: collaborator

Queensland University of Technology

OTHER

Sponsor Role: collaborator

Queensland Centre for Gynaecological Cancer

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas Obermair

Role: STUDY_CHAIR

Queensland Centre for Gynaecological Cancer

Locations

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

The Wesley Hospital

Auchenflower, Queensland, Australia

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Greenslopes Private Hospital

Greenslopes, Queensland, Australia

Mater Health Services, Brisbane

South Brisbane, Queensland, Australia

Mater Private Hospital

South Brisbane, Queensland, Australia

Gold Coast Hospital

Southport, Queensland, Australia

Townsville Hospital

Townsville, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Royal Women's Hospital

Carlton, Victoria, Australia

Monash Medical Centre

Clayton, Victoria, Australia

King Edward Memorial Hospital for Women

Perth, Western Australia, Australia

St John of God Hospital

Subiaco, Western Australia, Australia

Auckland City Hospital

Auckland, , New Zealand

Middlemore Hospital

Auckland, , New Zealand

Christchurch Women's Hospital

Christchurch, , New Zealand

Wellington Hospital

Wellington, , New Zealand

Countries

Australia; New Zealand

References

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.

Reference Type: DERIVED

PMID: 33762086 (View on PubMed)

Other Identifiers

feMMe

Identifier Type: -

Identifier Source: org_study_id