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

February 25, 2025 updated by: Ángel Lanas Arbeloa, Instituto de Investigación Sanitaria Aragón
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Spain
      • Zaragoza, Spain, 50009
        • Recruiting
        • Hospital Clinico Universitario Lozano Blesa
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1 (100 mg/24h)
Drug: acetylsalicylic acid
Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention
Experimental: Arm 2 (300 mg/24h)
Drug: acetylsalicylic acid
Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention
Experimental: Arm 3 (100 mg/12h)
Drug: acetylsalicylic acid
Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Assessment of changes in acetylation levels of COX enzymes in platelets and non-neoplastic and neoplastic colonic tissues
Time Frame: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Assessment of changes in prostaglandin E2 (PGE2) levels in colorectal mucosa depending on drug dosis
Time Frame: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
Assessment of changes in phosphorylated S6 protein (p-S6) levels in colorectal mucosa depending on drug dosis
Time Frame: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
Assessment of changes in thromboxane B2 (TxB2) levels in urine as indirect systemic biomarker depending on drug dosis
Time Frame: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
Assessment of changes in urinary metabolite 11-dehydro-TxB2 (TX-M) levels as indirect systemic biomarker depending on drug dosis
Time Frame: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
Assessment of changes in major urinary metabolite of PGE2 (PEG-M) levels depending on drug dosis
Time Frame: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto de Investigación Sanitaria Aragón

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
G. d'Annunzio University
Instituto de Salud Carlos III
Hospital Clínico Universitario Lozano Blesa

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ángel Lanas Arbeloa, MD, Instituto de Investigación Sanitaria Aragón

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 6, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 13, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 21, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PI17/01109
  • 2018-002101-65 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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