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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

This study has been terminated.
(Withdrawn due to poor accrual)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00566644
First received: November 30, 2007
Last updated: July 9, 2013
Last verified: October 2008
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prevention of Endometrial Tumors (POET)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Rate of atypical endometrial hyperplasia or endometrial cancer during the active follow-up period of the study [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: July 2007
Study Completion Date: August 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
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

  Eligibility

Ages Eligible for Study:   35 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00566644

Locations
United Kingdom
Basildon University Hospital
Basildon, England, United Kingdom, SS16 5NL
City Hospital - Birmingham
Birmingham, England, United Kingdom, B18 7QH
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Cheltenham General Hospital
Cheltenham, England, United Kingdom, GL53 7AN
Royal Devon and Exeter Hospital
Exeter, England, United Kingdom, EX2 5DW
Queen Elizabeth Hospital
Gateshead-Tyne and Wear, England, United Kingdom, NE9 6SX
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Liverpool Women's Hospital
Liverpool, England, United Kingdom, LV8 7SS
St. Georges, University of London
London, England, United Kingdom, SW17 ORE
Elizabeth Garrett Anderson Hospital
London, England, United Kingdom, WC1E 6DH
Guy's Hospital
London, England, United Kingdom, SE1 9RT
Chelsea Westminster Hospital
London, England, United Kingdom, SW10 9NH
St. Mary's Hospital
Manchester, England, United Kingdom, M13 0JH
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Great Western Hospital
Swindon, England, United Kingdom, SN3 6BB
Southend University Hospital NHS Foundation Trust
Westcliff-On-Sea, England, United Kingdom, SS0 0RY
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
Belfast, Northern Ireland, United Kingdom, BT8 8JR
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Ysbyty Gwynedd
Bangor, Wales, United Kingdom, LL57 2PW
University Hospital of Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
St George's, University of London
Investigators
Principal Investigator: Shirley Hodgson, MD St George's, University of London
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00566644     History of Changes
Other Study ID Numbers: CRUK-POET, CDR0000575423, EudraCT 2006-001815-30, EU-20784
Study First Received: November 30, 2007
Last Updated: July 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
endometrial cancer
hereditary non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2)

Additional relevant MeSH terms:
Colorectal Neoplasms, Hereditary Nonpolyposis
Endometrial Hyperplasia
Endometrial Neoplasms
Colonic Diseases
Colorectal Neoplasms
DNA Repair-Deficiency Disorders
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genetic Diseases, Inborn
Genital Diseases, Female
Genital Neoplasms, Female
Intestinal Diseases
Intestinal Neoplasms
Metabolic Diseases
Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms
Levonorgestrel
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents

ClinicalTrials.gov processed this record on November 20, 2014