Acetylsalicylic Acid and Colorectal Cancer Prevention: Exploring the Platelet Function of Its Mechanism of Action

NCT02125409 | Unknown Phase 3 DMC

• 2 other identifiers: D-13-012013-004269-15
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In a preliminary study in healthy subjects, the investigators determined the pharmacokinetic and pharmacodynamic of enteric-coated acetylsalicylic acid (ASA) (Adiro 100 mg, Bayer), and the variability (coefficient of variation), accuracy and precision of a novel biomarker of ASA action, i.e., quantification of the extent of COX-1 acetylation at serine-529, using a stable isotope dilution liquid chromatography multiple reaction monitoring/mass spectrometry (LC-MS) technique. Now, the investigators will perform a clinical study in individuals undergoing Colorectal cancer (CRC) to validate the hypothesis that that low-dose ASA given once daily is acting primarily by selectively acetylating platelet COX-1 and suppressing its activity throughout the 24-hour dosing interval. In contrast, it is expected that the inhibitory effect on extra-platelet sources of COX-1 will be short-lasting, if any, affecting only partially COX-1, and this effect will be completely reversed at 24 hours after dosing. This is an important point which will strengthen the platelet hypothesis underpinning the apparent adequacy of a 24-hour dosing interval of ASA administration for the anticancer effect detected in cardiovascular trials. These patients will be stratified into individuals with adenomas/carcinomas (20 to 30%) and patients without clinically detected adenomas/carcinomas (about 70 to 80%).

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Assessment of the degree of COX-1 acetylation by ASA administered for 1 week.

  It will be performed in platelets versus biopsies of the recto-colonic tissues.

  7 hours after the 7th daily dose (group 1) and 24 hours after the 7th daily dose (group 2)

Secondary Outcomes (7)

• Changes from baseline in different biomarkers.

  pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)

• Changes from baseline in eicosanoid generation in vivo by measuring urinary metabolites derived from COXs.

  pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)

• Changes in baseline platelet COX-1

  pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)

• Change from baseline in plasma proteins of markers of angiogenesis.

  pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)

• Assessment of ASA plasma levels.

  pre-drug on day 0 and after the 7th daily dose (6 hours for Group 1 and 24 hours for Group 2)

Study Arms (2)

Group 1

EXPERIMENTAL

Group 1, individuals will be treated with ASA for 1 week; then blood and tissue samples (during the screening colonoscopy) will be collected at from 6-7 h after the last dose of ASA.

Drug: Acetylsalicylic acid; Procedure: Screening colonoscopy

Group 2

EXPERIMENTAL

Group 2, individuals will be treated with ASA for 1 week; then blood and tissue samples (during the screening colonoscopy) will be collected at 24 hours after the last dose.

Drug: Acetylsalicylic acid; Procedure: Screening colonoscopy

Interventions

Acetylsalicylic acid DRUG

One tablet of Adiro 100 mg will be administered daily for 7 days.

Also known as: Adiro 100, ASA

Group 1; Group 2

Screening colonoscopy PROCEDURE

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, aged ≥ 18 and ≤ 69.
• Patients should have an indication for screening colonoscopy
• First degree relative of patient with CRC.
• Personal history of adenomas.
• People older than 50 and FOBT positive
• Routine hematological and biochemical parameters within the normal range.

You may not qualify if:

• Allergy to ASA or other NSAIDs.
• Previous use of ASA, NSAIDS, antiplatelet agents, corticosteroids or misoprostol in the previous 15 days and/or anticipated need for these drugs during the study period.
• Peptic ulcer history or any other gastrointestinal disease that could be considered a contraindication for ASA use without the concomitant use of a proton-pump inhibitor.
• Subjects with coagulation disorder or serious comorbid condition.
• Malignancies, excluding CRC, diagnosed in the previous 5 years
• Cigarette smoking, history of drug or alcohol abuse
• Pregnant women or breast feeding

Sponsors & Collaborators

• Aragon Institute of Health Sciences: lead
• G. d'Annunzio University: collaborator
• Catholic University, Italy: collaborator

Study Sites (1)

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Angel Lanas Arbeloa, Physician

  Digestive disease service of Hospital Clinico Lozano Blesa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2014
• First Posted: April 29, 2014
• Study Start: May 1, 2014
• Primary Completion: May 1, 2015
• Last Updated: May 5, 2014

Record last verified: 2014-05

Locations

ES (1)