Assessment of Direct Biomarkers of Aspirin Action to Develop a Precision Chemoprevention Therapy of Colorectal Cancer

NCT ID: NCT03957902

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-06
• Study Completion Date: 2025-06-30

Brief Summary

Acetylsalicylic acid (ASA) seems the ideal colorectal cancer (CRC) chemoprevention agent. Several ongoing trials are testing the effect of ASA as co-therapy in CRC. The mechanisms of action, the appropriate dose and the ideal target population are unknown. The investigators have demonstrated that doses of 100 mg of ASA induce direct and partial but persistent acetylation of the cyclooxygenase (COX) isoenzyme COX-1 in the normal colorectal mucosa. The primary objective is to perform a study of aspirin by using a proteomic assay for comparing platelet COX-1 and CRC mucosal COX-1 after different doses of ASA. Secondary objectives are: the measurement of prostaglandin E2 (PGE2) and phosphorylated S6 protein (p-S6) levels in CRC mucosa, the assessment of indirect biomarker of aspirin action (serum thromboxane B2 (TXB2) and urinary levels of 11-dehydro-TXB2 (TX-M)), the evaluation of systemic biomarkers of inflammatory/tumorigenic COX-2 by assessing urinary levels of major metabolite of PGE2 (PGE-M). Methods: Phase II randomized clinical trial in 60 patients with newly diagnosed CRC in 3 groups of 20 patients receiving 100 or 300 mg/day, or 100 mg/12 hours of enteric-coated ASA for 3±1 weeks, prior to definitive treatment by surgery. Main outcome: Acetylation of COX-1 and COX-2. Eicosanoid levels in target organs. Expected results: Evidence for the current uncertainty about the mechanisms of action and the dose required to obtain the best chemopreventive effect with ASA in CRC. Confirm acetylation of COX as a key biomarker of efficacy with ASA.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Arm 1 (100 mg/24h)

Group Type: EXPERIMENTAL

acetylsalicylic acid

Intervention Type: DRUG

Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention

Arm 2 (300 mg/24h)

Group Type: EXPERIMENTAL

acetylsalicylic acid

Intervention Type: DRUG

Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention

Arm 3 (100 mg/12h)

Group Type: EXPERIMENTAL

acetylsalicylic acid

Intervention Type: DRUG

Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention

Interventions

acetylsalicylic acid

Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• age ≥ 18 < 80 years old
• recent diagnosis (< 48h) of rectum or colon cancer, established by endoscopy and later confirmed by anatomo-pathologic study
• normal coagulation values and biochemical vales without clinically significant deviations that, at the discretion of the investigator, may interfere with the study procedures

Exclusion Criteria

• Allergy to ASA or to any other NSAID.
• Rectal cancer requiring neoadjuvant treatment within the two weeks following the beginning of ASA treatment.
• Previous use of ASA, NSAIDs, antiplatelet agents, corticosteroids or misoprostol within the 15 days prior to diagnosis and/or anticipation of need for treatment with any of these drugs during the study period. History of peptic ulcer disease or active peptic ulcer or any other gastrointestinal disease that may be considered a contraindication to the use of ASA, without the concomitant use of proton pump inhibitors.
• Diagnosis of bleeding disorders.
• Diagnosis of cancer (excluding non-melanoma skin cancer) within the previous 3 years.
• Conditions supposing serious comorbidity, excluding diabetes, and including respiratory, cardiac, hepatic and renal diseases.
• Active smoking.
• Pregnancy or breastfeeding.
• History of drug or alcohol abuse.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role: collaborator

G. d'Annunzio University

OTHER

Sponsor Role: collaborator

Hospital Clínico Universitario Lozano Blesa

OTHER

Sponsor Role: collaborator

Instituto de Investigación Sanitaria Aragón

OTHER

Sponsor Role: lead

Responsible Party

Ángel Lanas Arbeloa

Head of Digestive Diseases Service

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ángel Lanas Arbeloa, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Investigación Sanitaria Aragón

Locations

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Zaragoza, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Ángel Lanas Arbeloa, MD

Role: CONTACT

angel.lanas@gmail.com

0034976765786

Facility Contacts

Ángel Lanas Arbeloa, MD

Role: primary

angel.lanas@gmail.com

0034976765786

References

Patrignani P, Tacconelli S, Contursi A, Piazuelo E, Bruno A, Nobili S, Mazzei M, Milillo C, Hofling U, Hijos-Mallada G, Sostres C, Lanas A. Optimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action. Front Pharmacol. 2024 Feb 29;15:1362217. doi: 10.3389/fphar.2024.1362217. eCollection 2024.

Reference Type: DERIVED

PMID: 38495101 (View on PubMed)

Other Identifiers

2018-002101-65

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PI17/01109

Identifier Type: -

Identifier Source: org_study_id