Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

NCT ID: NCT03070574

Last Updated: 2019-04-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-24
• Study Completion Date: 2019-04-10

Brief Summary

Multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine, 1200mg mesalamine or placebo for prevention of colorectal neoplasia in Lynch Syndrome patients for 2 years.

Detailed Description

This is a multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine (5-ASA), 1200mg mesalamine (5-ASA) or placebo in LS patients for a 2-year treatment. 540 tumor free carriers of a known genetic mutation in a major MMR gene (including patients in which the polyps are endoscopically removed) will be randomized 1:1:1 (180 each) to receive 2400mg mesalamine, 1200mg mesalamine or placebo. Patients will be identified through local or national registries and through collaboration with sites. Tumor free patients, assessed by white light high resolution colonoscopy, will be randomized to the study. A serum and stool sample will be taken to identify for mesalamine compliance and potential biomarkers. Biopsies of the normal tissue of ascending colon and rectum will be taken at the first and the last colonoscopy.

The aim of the study is to investigate the effect of regular treatment with mesalamine (5-ASA) on the occurrence of any colorectal neoplasia, tumor multiplicity (the number of detected adenomas/carcinomas) and tumor progression in LS patients.

A 50% reduction of the occurrence of colorectal neoplasia in mesalamine-treated patients is expected. Tumor multiplicity and tumor progression (severity of the neoplastic lesions) will be investigated.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

2400 MG mesalamine (5-ASA) total

2400mg (1200mg mesalamine/1200mg) mesalamine once daily in the morning for the treatment phase of the study (24 months)

Group Type: EXPERIMENTAL

mesalamine 2400 MG (5-ASA)

Intervention Type: DRUG

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers, each 1200mg of IMP (= 2400 mg), every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

1200 MG mesalamine (5-ASA) total

placebo/1200mg mesalamine once daily in the morning for the treatment phase of the study (24 months)

Group Type: EXPERIMENTAL

mesalamine 1200 MG

Intervention Type: DRUG

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (1200 mg/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Placebo

Intervention Type: OTHER

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (placebo/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Placebo

placebo/placebo once daily in the morning for the treatment phase of the study (24 months)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (placebo/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Interventions

mesalamine 2400 MG (5-ASA)

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers, each 1200mg of IMP (= 2400 mg), every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Intervention Type: DRUG

mesalamine 1200 MG

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (1200 mg/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Intervention Type: DRUG

Placebo

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (placebo/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Intervention Type: OTHER

Other Intervention Names

Mezavant; Mesalazine; 5-aminosalicylic acid (5-ASA); Mezavant; Mesalazine; 5-aminosalicylic acid (5-ASA)

Eligibility Criteria

Inclusion Criteria

• Proven tumor-free (including patients in which the polyps are removed endoscopically) carriers of a germline pathologic mutation on one of the MMR genes including MLH1, MSH2 (including EpCAM) and MSH6
• Male or female subjects with the age > 25 years
• Females who have been post-menopausal more than one (1) year or females of childbearing potential using a highly efficient method of contraception with less than 1% failure rate (i.e. oral hormonal contraceptives, hormone implants, hormone injections, sterilization, hormonal or copper intrauterine device, sterilized/vasectomized partner, or diaphragm in combination with a condom, spermicide or birth control pills) or should agree to abstain from heterosexual activity during treatment period. Females of childbearing potential must have a negative pregnancy test at screening and before randomization.
• Signed written informed consent prior to inclusion in the study

Exclusion Criteria

• Presence of colorectal endoscopically non-removable benign neoplasia (patient can be included if the adenoma is removed)
• Carriers of germline mutations in PMS2
• Patients with history of stage 3 and 4 colorectal cancer (CRC) are excluded
• Presence of metastatic disease
• Regular use of acetylsalicylic acid (ASA or aspirin): daily use of ≥100mg in more than 3 continuous months within the last year
• Regular use of NSAIDs or COX-2 inhibitors: daily use in more than 3 continuous months within the last year
• Hypersensitivity to 5-ASA
• Patients after total or subtotal colectomy
• Colorectal surgery within the previous 6 months
• Unwillingness to participate or who is considered incompetent to give an informed consent
• Pregnant or breastfeeding women
• Participation in another clinical study investigating another IMP within 3 months prior to screening
• Renal insufficiency (GFR <30ml/min/1.73m2)
• Severe liver disease or liver failure (elevation of liver enzymes above 3xULN)
• Current or history of serious psychiatric disorder or alcohol/drug abuse that in the opinion of the investigator may impact the assessment of IMP safety andefficacy or protocol adherence
• Prior history of myocarditis or pericarditis. Other severe acute or chronic medical condition (such as severe chronic lung (COPD, including asthma), kidney or heart diseases) or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or ability to comply with study procedures, IMP administration and, in the judgment of the investigator, would make the subject inappropriate for entry into this study

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Prof. Dr. Gabriela Möslein, Germany

UNKNOWN

Sponsor Role: collaborator

Prof. Dr. Hans Vasen, The Netherlands

UNKNOWN

Sponsor Role: collaborator

Prof. Dr. med. Jan Lubinski, Poland

UNKNOWN

Sponsor Role: collaborator

Prof. Dr. med. Yaron Niv, Israel

UNKNOWN

Sponsor Role: collaborator

Univ. Prof. Dr. Judith Karner-Hanusch, Austria

UNKNOWN

Sponsor Role: collaborator

Ann-Sofie Backman, MD PhD, Sweden

UNKNOWN

Sponsor Role: collaborator

Christoph Gasche

OTHER

Sponsor Role: lead

Responsible Party

Christoph Gasche

Univ. Prof. Dr. Christoph Gasche - Coordinating Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Department of Surgery, Medical University Vienna

Vienna, , Austria

HELIOS Universitätsklinikum Wuppertal, Zentrum für Hereditäre Tumorerkrankungen

Wuppertal, North Rhine-Westphalia, Germany

Rabin Medical Center Beilinson Hospital Gastroenterology Department

Petah Tikva, , Israel

Leiden University Medical Center

Leiden, , Netherlands

Department of Genetics and Pathomorphology of Pomeranian Medical University

Szczecin, , Poland

Karolinska universitetsjukhuset, A6:00 Gastroenterologiskt öppenvårdscentrum, Mottagningen för ärftlig tarmcancer

Solna, , Sweden

Countries

Austria; Germany; Israel; Netherlands; Poland; Sweden

Other Identifiers

MesaCAPP

Identifier Type: -

Identifier Source: org_study_id

NCT02864979

Identifier Type: -

Identifier Source: nct_alias