Intrauterine Levonorgestrel and Observation or Observation Alone in Preventing Atypical Endometrial Hyperplasia and Endometrial Cancer in Women With Hereditary Non-Polyposis Colorectal Cancer or Lynch Syndrome

Sponsor

St George's, University of London (Other)

Overall Status

Terminated

CT.gov ID

NCT00566644

Collaborator

(none)

600

Enrollment

Locations

Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: The use of intrauterine levonorgestrel may prevent atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome. It is not yet known whether intrauterine levonorgestrel and observation are more effective than observation alone in preventing atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome.

PURPOSE: This randomized phase III trial is studying intrauterine levonorgestrel and observation to see how well they work compared with observation alone in preventing atypical endometrial hyperplasia and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer Hereditary Non-polyposis Colon Cancer (hmsh2, hmlh1, hpms1, hpms2)	Device: levonorgestrel-releasing intrauterine system Other: questionnaire administration Procedure: observation	Phase 3

Detailed Description

OBJECTIVES:

Primary

To determine if treatment with intrauterine levonorgestrel (using the Mirena® intrauterine system [IUS]) reduces the incidence of atypical endometrial hyperplasia (AEH) and endometrial cancer in women with hereditary non-polyposis colorectal cancer or Lynch syndrome.

Secondary

Determine the age-related incidence of AEH and endometrial cancer in these patients.
Determine the sensitivity and specificity of transvaginal sonography and endometrial biopsy in detecting AEH and endometrial cancer.
Determine the premalignant pathway to carcinoma.
Determine if the Mirena® IUS reduces the rate of therapeutic hysterectomy for AEH or endometrial cancer.
Determine the psychological benefits or adverse effects from the use of the Mirena® IUS.
Determine the satisfaction and compliance with screening.
Determine the extent of adverse effects of the Mirena® IUS and observation.
Determine the molecular changes associated with pre-malignant changes in the endometrium of these patients, and possibly the utility of tests on cervical mucus samples in diagnosing endometrial cancer.

OUTLINE: This is a multicenter study. Patients are stratified by center and menopausal status. Patients are randomized to 1 of 2 arms.

Arm I: Patients undergo insertion of the Mirena® intrauterine device containing levonorgestrel. The device is scheduled to remain in place for 4 years. Patients also undergo observation comprising an assessment of menstrual history, transvaginal scanning (TVS), and endometrial biopsy (or hysteroscopy) at baseline and then annually for 4 years.
Arm II: Patients undergo observation comprising an assessment of menstrual history, TVS, and endometrial biopsy (or hysteroscopy) at baseline and then annually for 4 years.

Patients complete a personal health and lifestyle questionnaire, the Life Events Scale, and the Profile of Mood States (POMS) questionnaires at baseline and periodically during study.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Prevention of Endometrial Tumors (POET)

Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

Aug 1, 2009

Outcome Measures

Primary Outcome Measures

Rate of atypical endometrial hyperplasia or endometrial cancer during the active follow-up period of the study []

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Proven to carry a pathogenic germline mutation in a DNA mismatch repair gene causing Lynch syndrome (hereditary non-polyposis colorectal cancer) (usually MSH2, MLH1, or MSH6)
Meets both of the following criteria:
Has a family history of Lynch syndrome according to the following Amsterdam or modified Amsterdam criteria:
Three relatives with a Lynch syndrome-related cancer (colorectal, small bowel, endometrial, ovarian, urothelial, or hepatobiliary)
One is a first-degree relative of the other two
Two generations affected
One relative diagnosed before age of 50
Personal history of colorectal cancer (i.e., a large, villous, or severely dysplastic colorectal adenoma) before the age of 40 OR history of small bowel, hepatobiliary, or urothelial cancer AND has an affected family member with an abnormal tumor immunohistochemistry staining for Lynch syndrome
No active genital malignancy, breast carcinoma, or other estrogen dependent tumor
History of genital malignancy, breast carcinoma, or other estrogen dependent tumor allowed at the discretion of the investigator

PATIENT CHARACTERISTICS:

Must have an intact uterus and not planning to undergo a prophylactic hysterectomy
Not pregnant
Not planning to become pregnant within the next 3 years
No abortion resulting in infection within the past 3 months
No pelvic inflammatory disease (PID) within the past 6 months or recurrent PID
No clinically significant submucous myomas requiring treatment
Small subserous or intramural myomas, clinically assessed as insignificant allowed
No known hypersensitivity to the constituents of the Mirena® IUS
No unresolved abnormal cervical smear and/or current cervical dysplasia
No trophoblastic disease with elevated hCG levels
No liver tumor or other acute or severe liver disease
No clinically significant condition or laboratory result that might, in the opinion of the investigator, compromise patient safety, interfere with evaluations, or prevent completion of the study
No other active malignancy
No history of stroke or myocardial infarction
No history of bacterial endocarditis or severe pelvic infection after any prosthetic valve replacement or in patients with an anatomical lesion of the heart

PRIOR CONCURRENT THERAPY:

No other concurrent use of intrauterine devices
No concurrent therapy for cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Basildon University Hospital	Basildon	England	United Kingdom	SS16 5NL
2	City Hospital - Birmingham	Birmingham	England	United Kingdom	B18 7QH
3	Addenbrooke's Hospital	Cambridge	England	United Kingdom	CB2 2QQ
4	Cheltenham General Hospital	Cheltenham	England	United Kingdom	GL53 7AN
5	Royal Devon and Exeter Hospital	Exeter	England	United Kingdom	EX2 5DW
6	Queen Elizabeth Hospital	Gateshead-Tyne and Wear	England	United Kingdom	NE9 6SX
7	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
8	Liverpool Women's Hospital	Liverpool	England	United Kingdom	LV8 7SS
9	Guy's Hospital	London	England	United Kingdom	SE1 9RT
10	Chelsea Westminster Hospital	London	England	United Kingdom	SW10 9NH
11	St. Georges, University of London	London	England	United Kingdom	SW17 ORE
12	Elizabeth Garrett Anderson Hospital	London	England	United Kingdom	WC1E 6DH
13	St. Mary's Hospital	Manchester	England	United Kingdom	M13 0JH
14	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PT
15	Great Western Hospital	Swindon	England	United Kingdom	SN3 6BB
16	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England	United Kingdom	SS0 0RY
17	Belfast City Hospital Trust Incorporating Belvoir Park Hospital	Belfast	Northern Ireland	United Kingdom	BT8 8JR
18	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
19	Ysbyty Gwynedd	Bangor	Wales	United Kingdom	LL57 2PW
20	University Hospital of Wales	Cardiff	Wales	United Kingdom	CF14 4XW