Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer) MedDRA version: 20.0 Level: PT Classification code 10051922 Term: Hereditary non-polyposis colorectal cancer syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Pentasa Sachet 2 g
Product Name: PENTASA SACHET 2 G
Product Code: [DK/H/0140/002]
Pharmaceutical Form: Prolonged-release granules for oral suspension
INN or Proposed INN: 5-ASA (ACIDO-5-AM
Sponsors
Karolinska Institutet - Department of Medicine, Solna
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 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 randomization. • Signed written informed consent prior to inclusion in the study 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 160 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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 • Patients with 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 • Patients after any subtotal or total colectomy • Colorectal surgery within the previous 6 months • Unwillingness to participate or who is considered unable 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 and efficacy 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), duodenal ulcer, haemorrhagic diathesis or psychiatric condition or other abnormal clinical sign 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 occurrence of any colorectal neoplasia (both benign and malignant tumors) 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. Advanced adenomas are defined by a diameter above 1 cm villous or tubulovillous histology or high grade dysplasia. - To investigate if differences between 5-ASA effects and placebo effects on the occurrence of colorectal neoplasia, tumor multiplicity or tumor progression depend on the history of colorectal cancer, sex and patients age (LS patients below 45 years of age or 45 years of age and older). - To determine the safety concerning 5-ASA in LS patients;Primary end point(s): Occurrence of any colorectal neoplasia (both benign and malignant tumors) between groups is described by absolute frequencies and percentages with 95 % confidence intervals. A logistic regression is used to assess differences between active treatment and placebo for the occurrence of any colorectal neoplasia, adjusted for country and history of cancer before randomization. Treatment effects are assessed by odds-ratios and corresponding 95 % confidence intervals.;Timepoint(s) of evaluation of this end point: Visits at 3, 12, 24 months. Conoscopy annually or every two years, and at the end of treatment (24 month +/- 1 month) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The number of colorectal neoplasia (both benign and malignant tumors)per patient will be tested between groups by an analysis of variance, adjusting for country and history of cancer before randomization. In case of non-normally distributed residuals a suitable transformation to achieve normal distribution is considered. • The tumor progress in the 4 ordered stages will be tested between groups by a chi-square trend test stratified for country and history of cancer before randomization and modelled by an ordinal logistic regression. • The dependence of treatment effects on history of colorectal cancer, sex and patients age (<45 years and =45 years) will be assessed by modelling interactions between these factors and treatment in the corresponding regression models. • Safety data are described and compared between groups in an exploratory manner. All tests are two-sided and a significance level of 5 % is used.;Timepoint(s) of evaluation of this end point: See primary endpoints | — |
Countries
Denmark, Israel, Italy, Poland, Sweden
Contacts
Public ContactDIMEC
Alma Mater Studiorum Università di Bologna
Outcome results
None listed