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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02864979
• Other study ID #: MesaCapp
• Status: Not yet recruiting
• Phase: Phase 2
• First received: July 28, 2016
• Last updated: August 9, 2016
• Start date: August 2016
• Est. completion date: July 2022

Study information

• Verified date: August 2016
• Source: Rabin Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: July 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• Proven carrier of a germline pathologic mutation on one of the MMR genes including MLH1, MSH2, MSH6 or PMS2 without tumors.

Exclusion Criteria:

• Regular use of aspirin (>1000mg per week), NSAIDs or COX-2 inhibitors within the previous 2 years.

• Hypersensitivity to 5-ASA.

• Patients after partial or total colectomy.

• Pregnancy.

• Severe concomitant disease.

• History of stage 1 ans 2 carcinoma within 6 months after surgery.

• Colonic neoplasm.

• Metastatic disease.

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

Intervention

Drug:
• Mesalamine 1600 mg QD
Mesalamine 1600 mg QD
• Mesalamine 3200 mg QD
Mesalamine 3200 mg QD
• Placebo
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Rabin Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of a colonic neoplasm after 24 months on the study drug or placebo.	Occurrence of a colonic neoplasm after 24 months on the study drug or placebo as detected by colonoscopy.	24 months	No
Secondary	The number of neoplasms (tumor multiplicity) per patient compared between placebo and 5-ASA (low- and high-dose together)	The number of neoplasms (tumor multiplicity) per patient compared between placebo and 5-ASA (low- and high-dose together)	24 months	No
Secondary	Tumor progress after 24 months	Tumor progress after 24 months (4 ordinal stages: no neoplasms / early adenoma / advanced adenoma / carcinoma) compared between placebo and 5-ASA (low- and high-dose together)	24 months	No