Assessment of direct biomarkers of aspirin action to develop a precision chemoprevention therapy of colorectal cancer

INTERVENTION: Trade Name: Adiro 100 mg Pharmaceutical Form: Coated tablet INN or Proposed INN: ACETYLSALICYLIC ACID CAS Number: 50‐78‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Adiro 300 mg Pharmaceutical Form: Coated tablet INN or Proposed INN: ACETYLSALICYLIC ACID CAS Number: 50‐78‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ CONDITION: Colorectal cancer with a recent confirmed diagnosis (less than 48h) ; MedDRA version: 20.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: to perform a study of acetylsalicylic acid by using a proteomic assay for comparing platelet COX‐1 and colorectal cancer mucosal COX‐1 and COX‐2 after different doses of acetylsalicylic acid Primary end point(s): Assessment of acetylation level of COX enzymes in platelets and non‐neoplastic and neoplastic colonic tissues Secondary Objective: measurement of PGE2 and p‐S6 levels in colorectal cancer mucosa, assessment of indirect biomarkers of acetylsalicylic acid action (serum TXB2, PFA and urinary levels of 11‐dehydro‐TXB2, (TX‐M)), evaluation of systemic biomarkers of inflammatory/tumorigenic COX‐2 by assessing urinary levels of major metabolite of PGE2 (PGE‐M) Timepoint(s) of evaluation of this end point: before the beginning of the treatment and 3‐4 weeks of acetylsalicylic acid treatment SECONDARY OUTCOME: Secondary end point(s): assessment of PGE2 level and S6 protein phosphorylation state in colorectal mucosa depending on AAS dosis and assessment of dosis effect e¡over indirect biomarkers Timepoint(s) of evaluation of this end point: before the beginning of the treatment and 3‐4 weeks of acetylsalicylic acid treatment INCLUSION CRITERIA: ‐ Age from 18 to 80 years old ‐ Recent diagnosis (less than 48h) of colorectal cancer by endoscopy and confirmed by anatomopathological study ‐ normal hematologic, biochemical, and coagulation values 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50