Colorectal CancerPhase 2NCT03957902
Assessment of Direct Biomarkers of Aspirin Action to Develop a Precision Chemoprevention Therapy of Colorectal Cancer
A Phase 2 study testing acetylsalicylic acid in people with Colorectal Cancer, run by Instituto de Investigación Sanitaria Aragón at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- acetylsalicylic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSpain
- Study dates
- 6 May 2019to Jun 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 9Show fewer
- Active smoking.
- Pregnancy or breastfeeding.
- History of drug or alcohol abuse.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Zaragoza, 50009
Ángel Lanas Arbeloa, MD, 0034976765786, angel.lanas@gmail.com
About this study
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
- Being tested
- acetylsalicylic acid
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
acetylsalicylic acidDrug
Different dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (100 mg/24h) | Experimental | Not described Receives: Drug: acetylsalicylic acid |
| Arm 2 (300 mg/24h) | Experimental | Not described Receives: Drug: acetylsalicylic acid |
| Arm 3 (100 mg/12h) | Experimental | Not described Receives: Drug: acetylsalicylic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of changes in acetylation levels of COX enzymes in platelets and non-neoplastic and neoplastic colonic tissues
Measured: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
Secondary outcomes (5)
Assessment of changes in prostaglandin E2 (PGE2) levels in colorectal mucosa depending on drug dosis
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: before the beginning of the treatment and 3 ± 1 weeks of acetylsalicylic acid treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2019
- Study start6 May 2019
- Primary completionMay 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación Sanitaria Aragón
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III, G. d'Annunzio University, Hospital Clínico Universitario Lozano Blesa
- Responsible party
- Principal investigator, Ángel Lanas Arbeloa, Instituto de Investigación Sanitaria Aragón
- Investigators
- Ángel Lanas Arbeloa, MD, Principal investigator, Instituto de Investigación Sanitaria Aragón
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03957902
- Sponsor's protocol ID
- PI17/01109
- Other IDs
- 2018-002101-65, 2018
- Status last verified
- Feb 2025
- First submitted
- 13 May 2019
- Last updated
- 27 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38495101
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Direct Biomarkers of Aspirin Action to Develop a Precision Chemoprevention Therapy of Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03957902
- Acronym / sponsor ID
- PI17/01109
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Instituto de Investigación Sanitaria AragónUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III, G. d'Annunzio University, Hospital Clínico Universitario Lozano Blesa
- Study start
- 6 May 2019 (actual)
- Primary completion
- May 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 21 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (100 mg/24h) | Experimental | Drug: acetylsalicylic acid |
| Arm 2 (300 mg/24h) | Experimental | Drug: acetylsalicylic acid |
| Arm 3 (100 mg/12h) | Experimental | Drug: acetylsalicylic acid |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| acetylsalicylic acidDifferent dosage effect over platelet COX enzymes, non- neoplastic and neoplastic colonic tissues used as biomarkers of clinical efficacy in CRC chemoprevention | Drug | Arm 1 (100 mg/24h), Arm 2 (300 mg/24h), Arm 3 (100 mg/12h) |
Primary outcome
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
5 secondary outcomes
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
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2025.
- Derived from this study: PubMed 38495101Patrignani 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ángel Lanas Arbeloa, MD principal investigator
Instituto de Investigación Sanitaria Aragón
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing acetylsalicylic acid in people with Colorectal Cancer, run by Instituto de Investigación Sanitaria Aragón at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ángel Lanas Arbeloa, MD (0034976765786, angel.lanas@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03957902, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.