CaPP3 Spai

Phase 1

Conditions: ynch Syndrome
MedDRA version: 20.0Level: LLTClassification code 10051981Term: Lynch syndromeSystem Organ Class: 100000004850
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2014-000411-14-ES

Lead Sponsor: AVARRBIOMED-FUNDACION MIGUEL SERVET

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 50

Inclusion Criteria

1. Age over 18.
2. Confirmed germline pathological variant in one of the mismatch repair genes; MSH2, MLH1, PMS2 or MSH6 or a 3’ EPCAM deletion associated with MSH2 silencing or be a carriers of a constitutional epimutation manifesting a classic Lynch syndrome phenotype.
3. Able to swallow tablets.
4. Willing to complete the CaPP3 consent process as described in the patient information sheet.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Regular use of an oral non-steroidal anti-inflammatory agent on long-term basis. Regular is defined as > 3 doses per week, for more than 3 months in the last 3 years.
2. Previous regular use of aspirin at a daily dose of 150mg or less does not exclude enrolment but duration and quantity need to be documented in detail. More than 3 months use of > 150mg or more per day in the last 3 years is an exclusión.
3. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.
4. Existing clinically significant liver impairment.
5. Existing renal failure defined as creatinine clearance <10ml/min
6. Confirmed active peptic ulcer disease within the previous three months.
7. Known bleeding diathesis or concomitant anticoagulant therapy.
8. Inability to comply with study procedures and agents.
9. Women reporting that they are pregnant or actively planning to achieve a pregnancy within the next two years.
10. Women who are breastfeeding.
11. Any significant medical illness that would interfere with study participation. (If hypertension is discovered, the participant should be advised to have this treated before commencing trial medication).
12. Bi-allelic Mismatch Repair Deficiency BMMRD (also known as Constitutional Mismatch Repair Deficiency).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine whether the cancer preventive properties of enteric coated aspirin in Lynch syndrome are dose sensitive by comparing overall cumulative Lynch syndrome cancer incidence rates annually from 5 years in people who took 100mg, 300mg or 600mg enteric coated aspirin for at least 2 years.;Primary end point(s): The number of new primary mismatch repair deficient cancers (Lynch syndrome cancers”) at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.;Timepoint(s) of evaluation of this end point: Five years after last recruit enters trial;Secondary Objective: • Compare overall primary colorectal cancers in the three treatment groups.<br>• Compare overall primary endometrial cancers in the three treatment groups.<br>• Compare overall cancers of all types,in the three treatment groups.<br>• Compare the burden of adverse events in three treatment groups.

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: • The number of new colorectal cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.<br>• The number of new endometrial cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.<br>• The number of new cancers of all types at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.;Secondary end point(s): • The number of new colorectal cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.<br>• The number of new endometrial cancers at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.<br>• The number of new cancers of all types at 5 years and beyond which develop in participants who remain on prescribed treatment for a minimum of 2 years.