Lynch Syndrome also known as HNPCC (non hereditary non polyposis colorectal cancer). MedDRA version: 17.0 Level: LLT Classification code 10051981 Term: Lynch syndrome System Organ Class: 100000004850
Conditions
Interventions
Trade Name: aspirin
Product Name: aspirin
Pharmaceutical Form: Coated tablet
INN or Proposed INN: acetylsalicylic acid
Concentration unit: mg milligram(s)
Concentration number: 300-
INN or Proposed IN
Sponsors
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age over 18 2. Proven MMR gene defect carrier 3. CAPP2 participants, at least 10 years since enrolled into that study 4. Willing to take randomised blinded dose (100, 300, 600mg) of aspirin for two years & self-report numbers of tablets taken 5. Agreement for indefinite clinical follow up with a minimum of 5 years 6. Availability of Micro satellite instability and or immunohistochemical analysis of mismatch repair proteins to establish whether any lesions are likely to be Lynch syndrome related, are all non-negotiable 7. Biobanking (bloods for DNA & serum) and sharing tissue sections to allow pharmacogenetic sub studies, FSP(Frame shift peptide) antibody testing and effects of aspirin on molecular tumour phenotype are desirable but not essential. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2750 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 250
Exclusion criteria
Exclusion criteria: 1. Regular use of a non-steroidal anti-inflammatory agent (except aspirin) on a prescription and/or long-term basis. Regular is defined as > 3 doses per week. 2. Regular use of aspirin (> 3 doses per week or on a prescription basis) that cannot be replaced with any one of the randomised arms of the study followed by 100mg dose. 3. Current methotrexate use. 4. Known aspirin intolerance or hypersensitivity, including aspirin-sensitive asthma. 5. Existing clinically significant liver impairment. 6. Existing renal failure defined as creatinine clearance <10ml/min. 7. Active peptic ulcer disease within the previous three months or any previous proven peptic ulcer. 8. Known bleeding diathesis or concomitant warfarin therapy. 9. Inability to comply with study procedures and agents. 10. Women reporting that they are pregnant or actively planning to achieve a pregnancy within the next two years. 11. Women who are currently breastfeeding. 12. Any significant medical illness that would interfere with study participation. 13. Previous participation in this trial. [Participation in the previous CAPP2 study will not exclude patients from this study. The protocol requires that it be at least 10 years since they joined CAPP2. Recruitment to CAPP2 closed in 2006].
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to find out which daily dose of Aspirin, 600mg or 300mg or 100mg, taken for 2 years is best at preventing cancers in patients with lynch syndrome. We will measure this by comparing the total number of Lynch Syndrome cancers (cancers that people with lynch syndrome are more likely to get) after a minimum of 5 years from study entry.;Secondary Objective: • Compare overall primary colorectal cancers in the three treatment groups • Compare overall primary endometrial cancers in the three treatment groups. • Compare overall cancers of all types,in the three treatment groups. • Compare the burden of adverse events in three treatment groups. . compare levels of antibodies against abnormal proteins released by Lynch Syndrome cancers. • Through a linked biobanking strategy: a)Identify reliable markers in the blood that predict future cancer development. This will help establish other cancer prevention strategies. b)Help identify the likely mechanism of action on tumour formation. c)Identify the influence of individual variability in aspirin metabolism. ;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
| Measure | Time frame |
|---|---|
| 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. • 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. • 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. • Changes at 2 & 5 years in the titre of frameshift peptide antibodies from commencement of the prescribed treatment. ;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. • 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. • 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. • Changes at 2 & 5 years in the titre of frameshift peptide antibodies from commencement of the prescribed treatment. | — |
Countries
United Kingdom
Outcome results
None listed