Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age30+
SponsorAnn-Sofie Backman
About this trial
Multicenter, multinational, randomized, 2-arm, double-blind, phase II clinical study with 2000mg mesalamine, or placebo for prevention of colorectal neoplasia in Lynch Syndrome patients during and following daily intake for 2 years.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Proven tumor-free (including patients in which the polyps are removed endoscopically) carriers of a germline pathologic mutation in one of the MMR genes including MLH1, MSH2 (including EpCAM) and MSH6
Male or female subjects with the age of 30 years or older
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
Disqualifiers
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 CRC are excluded
Presence of metastatic disease
Trial design
Design model
Parallel
Treatments tested in this trial
Mesalamine
DrugThe IMP will be supplied as sachets with slow-releasing granules.
Placebo
DrugThe IMP will be supplied as sachets with slow-releasing granules.
Treatment groups
150 Participants
are divided into 2 treatment groupsGroup A: MesalamineExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change in the occurrence of any colorectal neoplasia in LS patients
Occurrence of any colorectal neoplasia (both benign and malignant tumors) between groups is described by absolute frequencies and percentages.
Time frame
End of treatment at 24 months +/- 1 month2
Change in the occurrence of any colorectal neoplasia in LS patients
As above.
Time frame
End of study at year 6 +/- 3 months.Secondary outcomes
1
Tumour multiplicity
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. It will be tested whether 5-ASA (low- and high-dose together) reduces the number of any colorectal neoplasia (both benign and malignant tumors; tumor multiplicity) compared to placebo in LS patients at the end of treatment and end of study. Advanced adenomas are defined by a diameter above 1 cm villous or tubulo-villous histology or high grade dysplasia.
Time frame
End of treatment at 24 months +/- 1 month2
Tumour progress
The tumor progress in 4 ordered stages will be tested between groups stratified for country and history of cancer before randomization. It will be tested whether 5-ASA reduces tumor progression (compared 4 ordinal stages: no colorectal neoplasia / non-advanced adenoma / advanced adenoma / carcinoma) compared to placebo in LS patients at the end of treatment and end of study. Advanced adenomas are defined by a diameter above 1 cm villous or tubulo-villous histology or high grade dysplasia.
Time frame
End of treatment at 24 months +/- 1 month3
Treatment effects
The dependence of treatment effects on history of colorectal cancer, sex and patients age will be assessed by modelling interactions between these factors and treatment in the corresponding regression models. 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 will be investigated.
Time frame
End of treatment at 24 months +/- 1 month4
Significant findings & illnesses - adverse events
Safety data are described and compared between groups in an exploratory manner to determine the safety concerning 5-ASA in LS patient. Therefore significant findings/illnesses, reported after the start of the study and which meet the definition of an AE, will be recorded in the CRF. Intention to treat set: This analysis set includes subjects who were randomized (and received at least one dose study drug). This analysis set will be chosen for safety assessment.
Time frame
End of treatment at 24 months +/- 1 monthSponsors and contacts
Click on the lead sponsor to view all of their trials.
Ann-Sofie Backman
Lead sponsor
Karolinska University Hospital
Sponsor institution
The Swedish Research Council
Collaborator
Karolinska Institutet
Collaborator
Source ClinicalTrials.gov