A randomised double-blind dose non-inferiority trial of a daily dose of 600mg versus 300mg versus 100mg of enteric coated aspirin as a cancer preventive in carriers of a germline pathological mismatch repair gene defect, Lynch Syndrome.

Phase 3

Active, not recruiting

• Conditions: Lynch Syndrome; Cancer; Cancer - Any cancer; ynch Syndrome; Human Genetics and Inherited Disorders - Other human genetics and inherited disorders

• Registration Number: ACTRN12617000804381
• Lead Sponsor: Royal Melbourne Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-06-01
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: Active, not recruiting
• Sex: All
• Target Recruitment: 141

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.
; 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.

Exclusion Criteria

1. Regular use of a non-steroidal anti-inflammatory agent on a prescription and/or 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 exclusion
3. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.
4. Existing clinically significant liver impairment.
5. Existing renal failure.
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. Participation in the previous CAPP2 study will not exclude patients from this study, apart from the small number recruited less than 10 years previously; 1. Regular use of a non-steroidal anti-inflammatory agent on a prescription and/or 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 exclusion
3. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma.
4. Existing clinically significant liver impairment.
5. Existing renal failure.
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. Participation in the previous CAPP2 study will not exclude patients from this study, apart from the small number recruited less than 10 years previously

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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. Participants will be followed up to document whether a cancer has developed. In the event of a cancer, the primary physician will be consulted with to obtain further information and medical records reviewed. <br> [ Throughout the study (5 years) and for a ten year follow up period. Altogether 15 years.<br><br>];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. Participants will be followed up to document whether a cancer has developed. In the event of a cancer, the primary physician will be consulted with to obtain further information and medical records reviewed. <br> [ Throughout the study (5 years) and for a ten year follow up period. Altogether 15 years.<br><br>]