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

NCT ID: NCT00566644

Last Updated: 2013-07-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2009-08-31

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.

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

Conditions

Endometrial Cancer; Hereditary Non-polyposis Colon Cancer (hmsh2, hmlh1, hpms1, hpms2)

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Interventions

levonorgestrel-releasing intrauterine system

Intervention Type: DEVICE

questionnaire administration

Intervention Type: OTHER

observation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

St George's, University of London

OTHER

Sponsor Role: lead

Principal Investigators

Shirley Hodgson, MD

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Locations

Basildon University Hospital

Basildon, England, United Kingdom

City Hospital - Birmingham

Birmingham, England, United Kingdom

Addenbrooke's Hospital

Cambridge, England, 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

Guy's Hospital

London, England, United Kingdom

Chelsea Westminster Hospital

London, England, United Kingdom

St. Georges, University of London

London, England, United Kingdom

Elizabeth Garrett Anderson Hospital

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, United Kingdom

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Belfast, Northern Ireland, United Kingdom

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Ysbyty Gwynedd

Bangor, Wales, United Kingdom

University Hospital of Wales

Cardiff, Wales, United Kingdom

Countries

United Kingdom

Other Identifiers

CDR0000575423

Identifier Type: REGISTRY

Identifier Source: secondary_id

EudraCT 2006-001815-30

Identifier Type: -

Identifier Source: secondary_id

EU-20784

Identifier Type: -

Identifier Source: secondary_id

CRUK-POET

Identifier Type: -

Identifier Source: org_study_id