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

Endometrial Cancer Clinical Trial

Official title:

Prevention of Endometrial Tumors (POET)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00566644
• Other study ID #: CRUK-POET
• Secondary ID: CDR0000575423Eud
• Status: Terminated
• Phase: Phase 3
• First received: November 30, 2007
• Last updated: July 9, 2013
• Start date: July 2007
• Est. completion date: August 2009

Study information

• Verified date: October 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 600
• Est. completion date: August 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Colorectal Neoplasms, Hereditary Nonpolyposis
• Endometrial Cancer
• Endometrial Hyperplasia
• Hereditary Non-polyposis Colon Cancer (hmsh2, hmlh1, hpms1, hpms2)

Intervention

Device:
• levonorgestrel-releasing intrauterine system

Other:
• questionnaire administration

Procedure:
• observation

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	Basildon University Hospital	Basildon	England
United Kingdom	Belfast City Hospital Trust Incorporating Belvoir Park Hospital	Belfast	Northern Ireland
United Kingdom	City Hospital - Birmingham	Birmingham	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Cheltenham General Hospital	Cheltenham	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Queen Elizabeth Hospital	Gateshead-Tyne and Wear	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Liverpool Women's Hospital	Liverpool	England
United Kingdom	Chelsea Westminster Hospital	London	England
United Kingdom	Elizabeth Garrett Anderson Hospital	London	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	St. Georges, University of London	London	England
United Kingdom	St. Mary's Hospital	Manchester	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Great Western Hospital	Swindon	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England

Sponsors (1)

Lead Sponsor	Collaborator
St George's, University of London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of atypical endometrial hyperplasia or endometrial cancer during the active follow-up period of the study			No