AAS-Lynch - Assessment of the effect of a daily chemoprevention by aspirin low-dose of new or recurrent colorectal adenomas in patients with Lynch syndrome

Phase 3

Active, not recruiting

• Conditions: Colorectal adenomas; Lynch syndrome
• Interventions: Drug: Acetylsalicylic acid lysinate 300 mg; Drug: Placebo (for Aspirin 300); Drug: Acetylsalicylic acid lysinate 100 mg; Drug: Placebo 100 (for Aspirin 100)

• Registration Number: 2024-516601-23-00
• Lead Sponsor: Assistance Publique Hopitaux De Paris

Brief Summary

To explore a preventive effect of aspirin low-dose (100 or 300 mg/d) compared with placebo on apparition of a new or recurrent colorectal adenomas in patients with Lynch syndrome.

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 Timeline

• Study First Posted: 2024-09-25
• Last Update Posted: 2025-03-13

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 852

Inclusion Criteria

Men and women 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

A colonoscopy done within 180 days prior to inclusion, with removal of all polyps endoscopically resectable

Patients accept that not use aspirin regularly all along the study (during 7 consecutive days during at least 3 weeks per year or during more than 21 days per year)

Effective contraception for womens of childbearing age, defined by a hormonal method, an intrauterine device (IUD), or surgical sterilization of the patient or her partner

Patients covered by French Social Security (AME not accepted)

Patients signed informed consent

Exclusion Criteria

History of total colectomy

Gastrointestinal bleeding linked to ulcerative disease in the previous 12 months before inclusion

Gastric pathology deemed significant by the investigator and not corrected by appropriate treatment

Uncontrolled hypertension

Kidney failure (creatinine clearance < 30 ml/mn)

Severe hepatic impairment (defined as TP <70%)

Severe uncontrolled heart failure

G6PD deficiency

Recent diagnosis of colorectal cancer implying a specific management

Menorrhagia deemed significant by the investigator and not corrected by appropriate treatment

Pregnancy or breast feeding

Adenomatous polyposis related to a known alteration of the APC gene or the MYH gene

Any disease susceptible to interfere with protocol-defined follow-up or to impair the comprehension of the information provided by the protocol and informed consent

Patient waiting for or have been signified a justice decision

Participation to another clinical trial during the 12 weeks before inclusion

Allergy to aspirin (including a history of asthma induced by the administration of salicylates or substances with similar activity, including non-steroidal anti-inflammatory)

Allergy to one food coloring potentially used in a chromo-endoscopy (indigo carmine, for example)

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)

Need for a prolonged and high-dose systemic glucocorticoid therapy

Known disease affecting primary hemostasis or coagulation (gastrointestinal bleeding, hemorrhagic stroke and thrombocytopenia history)

Need for a prolonged anticoagulant, antiplatelet agents, anagrelide, uricosurics, probenecid, ticagrelor, nicorandil, defibrotide, clopidogrel, ticlopidine, ticagrelor, ibrutinib, or cobimetinib

History of gastro-duodenal ulcer

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Aspirin300	Acetylsalicylic acid lysinate 300 mg	Acetylsalicylic acid 300 mg tablet by mouth, daily dose during 4 years
Placebo300	Placebo (for Aspirin 300)	Placebo (like Acetylsalicylic acid 300 mg) tablet by mouth, daily dose during 4 years
Aspirin100	Acetylsalicylic acid lysinate 100 mg	Acetylsalicylic acid 100 mg tablet by mouth, daily dose during 4 years
Placebo100	Placebo 100 (for Aspirin 100)	Placebo (like Acetylsalicylic acid 100 mg) tablet by mouth, daily dose during 4 years

Primary Outcome Measures

Name	Time	Method
Number of patients with at least 1adenoma on chromoendoscopy 48months after complete withdrawal of polyps and initiation of IMP. Only neoplastic polyps (progress to cancer), defined by the following histological types as determined by ACP result, will be considered: 1) Adenoma not otherwise specified 2) Tubular adenoma 3) Tubulovillous adenoma 4) Mixed or serrated adenoma (sessile serrated adenoma) 5) Villous adenoma. Additionally, cancers will also be considered for primary endpoint analysis		Number of patients with at least 1adenoma on chromoendoscopy 48months after complete withdrawal of polyps and initiation of IMP. Only neoplastic polyps (progress to cancer), defined by the following histological types as determined by ACP result, will be considered: 1) Adenoma not otherwise specified 2) Tubular adenoma 3) Tubulovillous adenoma 4) Mixed or serrated adenoma (sessile serrated adenoma) 5) Villous adenoma. Additionally, cancers will also be considered for primary endpoint analysis

Secondary Outcome Measures

Name	Time	Method
Delay between the onset of 1 adenoma after complete resection of polyps and date of start of treatment (aspirin vs placebo)		Delay between the onset of 1 adenoma after complete resection of polyps and date of start of treatment (aspirin vs placebo)
Number of patients who presented an adenoma during follow-up based on the gene reached (MLH1, MSH2, MSH6, PMS2, or without other identified anomalies)		Number of patients who presented an adenoma during follow-up based on the gene reached (MLH1, MSH2, MSH6, PMS2, or without other identified anomalies)
Load serrated polyps after 24 and 48 months of treatment		Load serrated polyps after 24 and 48 months of treatment
Adenomatous polyp burden, measured by chromoendoscopy as the sum of the size of all adenomatous polyps as a function of the dose of ASA (100 or 300 mg)		Adenomatous polyp burden, measured by chromoendoscopy as the sum of the size of all adenomatous polyps as a function of the dose of ASA (100 or 300 mg)
Load measured by polyps chromoendoscopy as the sum of the size of all polyps according to the aspirin dose (100 or 300mg)		Load measured by polyps chromoendoscopy as the sum of the size of all polyps according to the aspirin dose (100 or 300mg)
Colon cancers diagnosed during the scheduled surveillance colonoscopies		Colon cancers diagnosed during the scheduled surveillance colonoscopies
Time to onset of colon cancer diagnosed during the scheduled surveillance colonoscopies		Time to onset of colon cancer diagnosed during the scheduled surveillance colonoscopies
Cancers of the colon interval (diagnosed between 2 surveillance colonoscopies programmed)		Cancers of the colon interval (diagnosed between 2 surveillance colonoscopies programmed)
Time to onset of interval colorectal cancer		Time to onset of interval colorectal cancer
Number of colonoscopies performed during follow-up in study		Number of colonoscopies performed during follow-up in study
Quality of preparation before colonoscopy		Quality of preparation before colonoscopy
Chromoendoscopy expected execution		Chromoendoscopy expected execution
Counting of remaining tablets in blisters		Counting of remaining tablets in blisters
Number of events or side effects		Number of events or side effects
Food frequency		Food frequency
Distribution of the bacterial population based on two groups (treated / untreated) and recidivism		Distribution of the bacterial population based on two groups (treated / untreated) and recidivism
Distribution of polymorphisms based on 2 groups (treated / untreated) and recidivism		Distribution of polymorphisms based on 2 groups (treated / untreated) and recidivism
Proportion of patients with at least one adenoma seen on chromo-endoscopy within 48 months after complete polyp resection and the start of treatment (aspirin vs placebo)		Proportion of patients with at least one adenoma seen on chromo-endoscopy within 48 months after complete polyp resection and the start of treatment (aspirin vs placebo)

Trial Locations

Locations (23)

Hospices Civils De Lyon; 🇫🇷 Lyon Cedex 03, France

Institut Curie; 🇫🇷 Saint-Cloud, France

Centre Hospitalier Regional De Marseille; 🇫🇷 Marseille, France

Assistance Publique Hopitaux De Paris; 🇫🇷 Bobigny Cedex, France

Centre Hospitalier D Auxerre; 🇫🇷 Auxerre, France

Centre Antoine Lacassagne; 🇫🇷 Nice Cedex 2, France

CHRU De Nancy; 🇫🇷 Vandoeuvre Les Nancy Cedex, France

Institut De Cancerologie De L Ouest; 🇫🇷 Saint-Herblain Cedex, France

Centre Hospitalier Universitaire Reims; 🇫🇷 Reims, France

Centre Hospitalier Et Universitaire De Limoges; 🇫🇷 Limoges, France

Scroll for more (13 remaining)

Hospices Civils De Lyon

🇫🇷Lyon Cedex 03, France

Jean-Christophe SAURIN

Site contact

0472110111

jean-christophe.saurin@chu-lyon.fr