Clinical trial NCT00566644: 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
Official title: Prevention of Endometrial Tumors (POET)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Endometrial Cancer
Hereditary Non-polyposis Colon Cancer (hmsh2, hmlh1, hpms1, hpms2)
Keywords: endometrial cancer
hereditary non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2)
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-12-03
Enrollment: 600
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

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

Eligibility 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

Primary outcomes:
measure: Rate of atypical endometrial hyperplasia or endometrial cancer during the active follow-up period of the study
Secondary outcomes:
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: England
city: Birmingham
country: United Kingdom
facility: City Hospital - Birmingham
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Gateshead-Tyne and Wear
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Liverpool Women's Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: Chelsea Westminster Hospital
state: England
city: London
country: United Kingdom
facility: St. Georges, University of London
state: England
city: London
country: United Kingdom
facility: Elizabeth Garrett Anderson Hospital
state: England
city: Manchester
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Swindon
country: United Kingdom
facility: Great Western Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust Incorporating Belvoir Park Hospital
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: St George's, University of London
name: Shirley Hodgson, MD
role: PRINCIPAL_INVESTIGATOR
References: