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

• ClinicalTrials.gov Identifier: NCT02813824
• Recruitment Status: Recruiting
• First Posted: June 27, 2016
• Last Update Posted: October 26, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Lynch Syndrome	Drug: Acetylsalicylic acid lysinate 300 mg; Drug: Placebo (for Aspirin 300); Drug: Acetylsalicylic acid lysinate 100 mg; Drug: Placebo 100 (for Aspirin 100)	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 852 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Assessment of the Effect of a Daily Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome
• Actual Study Start Date: November 14, 2017
• Estimated Primary Completion Date: November 15, 2024
• Estimated Study Completion Date: December 15, 2025

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: Placebo100

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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 ]
2. 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 ]
3. Load serrated polyps after 24 and 48 months of treatment [ Time Frame: 24 and 48 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Zahia BEN ABDESSELAM; 33148957435; zahia.ben-abdesselam@aphp.fr

Locations

France

Hôpital Avicenne; Recruiting

Bobigny, France, 93000

Contact: Robert BENAMOUZIG, Pr robert.benamouzig@aphp.fr

Contact: Amal BOURKEB amal.bourkeb@aphp.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Soualy A, Deutsch D, Benallaoua M, Ait-Omar A, Mary F, Helfen S, Boubaya M, Levy V, Benamouzig R; AAS-Lynch group. Effect of chemoprevention by low-dose aspirin of new or recurrent colorectal adenomas in patients with Lynch syndrome (AAS-Lynch): study protocol for a multicenter, double-blind, placebo-controlled randomized controlled trial. Trials. 2020 Sep 4;21(1):764. doi: 10.1186/s13063-020-04674-8.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02813824
• Other Study ID Numbers: P130937
• First Posted: June 27, 2016
• Last Update Posted: October 26, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenoma; Colorectal Neoplasms, Hereditary Nonpolyposis; Syndrome; Disease; Pathologic Processes; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Metabolic Diseases; Aspirin; Acetylsalicylic acid lysinate; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents