POET: Prevention Of Endometrial Tumours

Recruitment & Eligibility

Status: Completed

Sex: Female

Target Recruitment: 220

Inclusion Criteria

Women aged 35 to 65 years are eligible if:
1. Proven to carry a pathogenic germline mutation in a DNA mismatch repair gene causing Lynch syndrome (usually MSH2, MLH1, MSH6)
2. Women:
a. from a family fulfilling the Amsterdam or the modified Amsterdam criteria for Lynch syndrome (three relatives with an Lynch syndrome-related cancer (colorectal, small bowel, endometrial, ovarian, urothelial or hepatobiliary), one the first-degree relative of the other two, two generations affected, and one diagnosis before the age of 50 years)

AND

b. who themselves have had colorectal cancer, a large, villous or severely dysplastic colorectal adenoma before the age of 40 years, or small bowel, hepatobiliary, or urothelial cancer, and where abnormal immunohistochemistry staining for Lynch syndrome proteins in the tumour has been demonstrated in an affected family member.

The aim is to randomise 220 women within 18 months of opening the trial. However, randomising as many as 800 women could be justified in order to evaluate the effect of Mirena separately pre- and post-menopause.

3. Risk equivalent
A patient may be randomised in the POET trial if it can be proved that she is a carrier. For example, this could be due to the woman being an obligate carrier in a family meeting the Amsterdam Criteria and including other evidence of a mis-match repair defect.

Having a ?risk equivalent? entry point will also allow for someone who was only a second degree relative of an affected family member, but who herself had had bowel cancer at age 35, for instance, to be eligible in the trial.

Eligibility will be confirmed in writing by Prof. Hodgson, Dr Sheridan or Dr Murday and a copy of the email/letter will be kept with the patient?s notes for monitoring purposes.

Exclusion Criteria

1. Women without an intact uterus (or who are planning a prophylactic hysterectomy)
2. Known or suspected pregnancy
3. Women trying to become pregnant in the next three years
4. Infected abortion during the three months before Mirena insertion is planned
5. Concomitant use of intrauterine devices
6. History of, or active, genital malignancy or breast carcinoma or other oestrogen dependent tumours
7. Any kind of active malignancy
8. Currently on therapy for cancer
9. Pelvic inflammatory disease (PID) during previous 6 months (before the Mirena IUS insertion) or recurrent PID
10. Clinically significant submucous myomas requiring treatment. Small subserous or intramural myomas, clinically assessed as insignificant, are acceptable
11. Any known hypersensitivity to the constituents of the Mirena IUS
12. An unresolved abnormal cervical smear
13. Trophoblastic disease while hCG levels remain elevated
14. Any clinically significant condition or laboratory result that might, in the opinion of the investigator, compromise patient safety, interfere with the evaluations or prevent the completion of the trial
15. Outside the age-range for the study
16. Current or previous severe arterial disease (Stroke, M1) or severe liver disease