E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lynch Syndrome, which is increasing the risk of developing colorectal cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Lynch Syndrome, which is increasing the risk of developing colorectal cancer. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051981 |
E.1.2 | Term | Lynch syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
- 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of any colorectal neoplasia (both benign and malignant tumors). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomisation until the end of follow-up. |
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From randomisation until the end of follow-up. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |