Lynch Syndrome, which is increasing the risk of developing colorectal cancer. MedDRA version: 20.0 Level: LLT Classification code 10051981 Term: Lynch syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Pentasa Sachet 2 g
Product Name: Pentasa Sachet
Pharmaceutical Form: Coated granules in sachet
Pharmaceutical form of the placebo: Coated granules in sachet
Route of administration of the
Sponsors
Karolinska Institute
Eligibility
Sex/Gender
All
Inclusion 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 > 30 years. - Females who have been post-menopausal more than one (1) year or females of childbearing potential using a highly efficient method of contraception. - Signed written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 130 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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. - History of stage 3 and 4 colorectal cancer (CRC). - Presence of any 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. - Subtotal or total colectomy. - Colorectal surgery within the previous 6 months. - Unwillingness to participate or considered unable to give an informed consent. - Pregnancy or ongoing breastfeeding. - 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 and efficacy or protocol adherence - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test whether mesalamine (5-ASA) reduces the occurence of any colorectal neoplasia (both benign and malignant tumours) compared to placebo in Lynch syndrome (LS) patients as detected by any colonoscopy until the end of treatment (24 months +/- 1 month) and end of study.;Secondary Objective: - To test whether 5-ASA reduces the number of any colorectal neoplasia, both benign and malignant tumors, (tumor multiplicity) and tumor progression to placebo in LS patients at defined time points. - To investigate if the effect of 5-ASA depend on the history of colorectal cancer, sex and patients age. - To determine the safety concerning 5-ASA in LS patients. Descriptive objectives: - Tumor occurrence in the right and left colon and rectum and the occurrence and location of serrated benign or malignant colorectal neoplasia are described for the two treatment groups. - To investigate the differences of colorectal neoplasia, tumor multiplicity or tumor progression as described for each sublocation. - To investigate if the effects of 5-ASA differs between major genotypes specific for LS. - To determine compliance concerning 5-ASA in LS patients;Primary end point(s): Occurrence of any colorectal neoplasia (both benign and malignant tumors).;Timepoint(s) of evaluation of this end point: From randomisation until the end of follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The number of colorectal neoplasia (both benign and malignant tumors) per patient. - The tumor progress in the 4 ordered stages. - The dependence of treatment effects on history of colorectal cancer, sex and patients age (<45 years and =45 years). - Amount and severity of adverse events.;Timepoint(s) of evaluation of this end point: From randomisation until the end of follow-up. | — |
Countries
Denmark, Sweden
Contacts
Public ContactPrincipal Investigator
Karolinska Institute
Outcome results
None listed