Effect of Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome (AAS-Lynch)

June 27, 2022 updated by: Assistance Publique - Hôpitaux de Paris

Assessment of the Effect of a Daily Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome

The proposed trial will evaluate the effect of aspirin 300 mg/d and 100 mg/d during 4 years vs placebo, in a 4 groups randomised parallel design in Lynch syndrome patients: patients with proven carriers of pathological mutations in mismatch repairs genes and patients with personal and family history characterizing Lynch syndrome according to modified Amsterdam criteria without proven mutation, aged more than 18 years with signed informed consent. The main hypothesis to be tested is that aspirin could decrease colorectal adenoma recurrence evaluated during high quality follow-up by colonic chromo-endoscopy in Lynch syndrome patients. The trial will also explore: (i) colorectal neoplasia recurrence according to different germline alteration in mismatch repair genes, (ii) observance to chemoprevention in Lynch syndrome patients, (iii) the burden of adverse events attributable to aspirin in Lynch syndrome patients, (iv) the dose-effect of aspirin on adenomatous polyp burden. All pathological samples will be reviewed using a centralized procedure. The INCA regional network organization and the HNPCC patient organization will allow the recruitment and the follow-up of a large number of patients with well characterised Lynch syndrome.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Lynch syndrome (LS) is the most common inherited colorectal cancer syndrome, and results from germline mutations in mismatch repair genes that confer a high lifetime risk of colorectal cancer (CRC) (60 to 70%). Most CRCs arise from asymptomatic polyps. Development of such polyps into cancer can be prevented if polyps are detected early by endoscopy and removed. Colonoscopy is proposed every 2 years in LS patients more than 25 years old, and every year when colonic neoplasia has been detected. Efficient chemoprevention has the potential to represent a cost-effective intervention in these patients and could allow a delay in colonoscopic surveillance.

Several epidemiological studies have shown that regular use of low dose aspirin (75 to 300 mg/d) is associated with a 20 to 30 % reduction in the risk of sporadic colonic polyps and CRC. Four randomised controlled trials (RCT) have also shown a decrease in colorectal polyp recurrence. In a pooled analysis of cardio-vascular prevention RCTs, as well as in a meta-analysis, daily aspirin was associated with a reduced risk of CRC and CRC associated mortality. Aspirin preventive benefit is expected to outweigh its putative side effects in high risk patients. The CAPP2 study in Lynch syndrome patients showed that aspirin (300 mg x2/d) did not reduce significantly the risk of colorectal neoplasia after 29 months, but an extended follow-up (mean 56 months) showed a reduction in colorectal cancer in the aspirin group. In this study, the endoscopic follow-up was not optimal with a relatively low detection rate of colorectal neoplasia according to usual reported rate when chromo-endoscopy is performed. So, the real effect and clinical benefit of aspirin are still to be characterised in Lynch syndrome patients.

Study Type

Interventional

Enrollment (Anticipated)

852

Phase

  • Phase 3

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 Locations

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

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient with Lynch syndrome bearing an alteration of "mismatch repair" genes or,when no characteristic alteration has been found, with a personal or family history of Lynch syndrome according to modified Amsterdam criteria
  • Aged more than 25 years, et aged more than 18 years with an early familial history and any reason to perform a colonoscopy every 2 years
  • Aged less than 75 years

Exclusion Criteria:

  • Known allergy to aspirin (including a history of asthma induced by the administration of salicylates or substances with similar activity, including non-steroidal anti-inflammatory)
  • Need for a prolonged treatment (prevention of cardio-vascular risk) or repeated treatments (recurring migraines) using aspirin or another non-steroidal anti-inflammatory drug (NSAID)
  • Pregnancy or breast feeding
  • Participation to another clinical trial during the 12 weeks before inclusion

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: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Aspirin300
Acetylsalicylic acid 300 mg tablet by mouth, daily dose during 4 years
Drug: Acetylsalicylic acid lysinate 300 mg
Daily dose during 4 years
Other Names:
  • Aspirin300
Placebo Comparator: Placebo300
Placebo (like Acetylsalicylic acid 300 mg) tablet by mouth, daily dose during 4 years
Drug: Placebo (for Aspirin 300)
Daily dose during 4 years
Other Names:
  • Placebo300
Active Comparator: Aspirin100
Acetylsalicylic acid 100 mg tablet by mouth, daily dose during 4 years
Drug: Acetylsalicylic acid lysinate 100 mg
Daily dose during 4 years
Other Names:
  • Aspirin100
Placebo Comparator: Placebo100
Placebo (like Acetylsalicylic acid 100 mg) tablet by mouth, daily dose during 4 years
Drug: Placebo 100 (for Aspirin 100)
Daily dose during 4 years
Other Names:
  • Placebo100

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with at least one adenoma seen on chromo-endoscopy 48 months after complete withdrawal of polyps and initiation of treatment (aspirin or placebo)
Time Frame: 4 years
To look for a preventive effect of low-dose aspirin (100 or 300 mg/d) compared with placebo on new or recurrent colorectal adenomas in patients with Lynch syndrome
4 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Delay between the onset of 1 adenoma after complete resection of polyps and date of start of treatment (aspirin vs placebo)
Time Frame: 24 and 48 months
24 and 48 months
Number of patients who presented an adenoma during follow-up based on the gene reached (MLH1, MSH2, MSH6, PMS2, or without other identified anomalies)
Time Frame: 24 and 48 months
24 and 48 months
Load serrated polyps after 24 and 48 months of treatment
Time Frame: 24 and 48 months
24 and 48 months

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Robert BENAMOUZIG, Pr, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

November 14, 2017

Primary Completion (Anticipated)

June 15, 2026

Study Completion (Anticipated)

December 15, 2027

Study Registration Dates

First Submitted

June 23, 2016

First Submitted That Met QC Criteria

June 23, 2016

First Posted (Estimate)

June 27, 2016

Study Record Updates

Last Update Posted (Actual)

June 28, 2022

Last Update Submitted That Met QC Criteria

June 27, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P130937

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

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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