Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

Colorectal Neoplasms, Hereditary Nonpolyposis Clinical Trial

Official title: Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

Status Not yet recruiting

Clinical Trial Summary

This is a clinical prevention trial of mesalamine in patients with LS (Lynch syndrome). tumor free carriers of a known genetic mutation in a major (mismash repair) MMR gene will be randomized 1:1:1 to receive 3600mg 5-ASA (mesalamine), 1600mg 5-ASA, or placebo. Patients will be identified through local or national registries and through collaboration with satellite centers. Tumor free patients, assessed by colonoscopy, will be allocated to the study. After a 2-year intervention phase patients will be assessed by colonoscopy for the presence of colonic neoplasia. The investigators expect a 50% reduction of neoplasia in 5-ASA-treated patients. Secondary endpoints are tumor multiplicity and trend analysis for the severity of the neoplastic lesion.

Clinical Trial Description

Background and rationale:

Lynch syndrome patients with a mutation in one of the DNA repair genes (MLH1, PMS2, MSH2, MSH6) have a 50% chance to develop colorectal cancer.

The occurrence of Lynch syndrome is estimated to be between 1:2000 and 1:370 people in western countries population.

Preventative medical treatment could be a meaningful addition to the bi-yearly endoscopic follow-up in these patients.

Development cancer in Lynch syndrome occurs through a mechanism of MSI (microsatellite instability). The loss of function of the DNA repair genes causes the phenotype of recurrent sequences of bases that are called microsatellite.

Mesalamine was proven in vitro to be tolerable for many years in IBD (inflammatory bowel disease) and apparently prevents development of bowel cancer In IBD patients.

The investigators hypothesis is that Mesalamine will prevent development of colorectal cancer in Lynch syndrome patients that are followed up with endoscopy.

Population size: 20, male and female.

Screening: patients will go through a colonoscopy and biopsies, blood tests, urine and stools will be taken. In addition, medical history, and vital signs will be collected.

Randomization:

Patients will be allocated to one of three arms (1:1:1): 3200 mg mesalamine, 1600 mg mesalamine or placebo.

Every 6 months patients will come to be assessed by a doctor and give blood samples.

Every 4-8 weeks patients will be contacted on the phone for compliance and safety assessment.

Every year, patients will undergo a colonoscopy, and biopsies will be taken. After two years they will have a final colonoscopy. Biopsies, blood, urine and stool will be taken to be tested.

After 5 years - follow-up. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Colorectal Neoplasms, Hereditary Nonpolyposis

• NCT number: NCT02864979
• Study type: Interventional
• Source: Rabin Medical Center
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 2016
• Completion date: July 2022