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

Phase

Condition

Colon Cancer

Precancerous Condition

Colorectal Cancer

Treatment

Acetylsalicylic acid lysinate 300 mg

Placebo 100 (for Aspirin 100)

Placebo (for Aspirin 300)

Clinical Study ID

NCT02813824

P130937

Ages 18-75
All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Patient with Lynch syndrome bearing an alteration of "mismatch repair" genes or,whenno characteristic alteration has been found, with a personal or family history ofLynch syndrome according to modified Amsterdam criteria
Aged more than 25 years, et aged more than 18 years with an early familial historyand any reason to perform a colonoscopy every 2 years
Aged less than 75 years

Exclusion

Exclusion Criteria:

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

Study Design

Acetylsalicylic acid lysinate 300 mg

November 14, 2017

December 15, 2027

Study 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.

Connect with a study center

Hôpital Avicenne
Bobigny, 93000
France
Site Not Available

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