Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome (MesaCAPP)
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|ClinicalTrials.gov Identifier: NCT04920149|
Recruitment Status : Recruiting
First Posted : June 9, 2021
Last Update Posted : March 28, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Lynch Syndrome Colon Cancer Colon Neoplasm||Drug: Mesalamine Drug: Placebo||Phase 2|
This is a multicenter, multinational, randomized, 2-arm, double-blind, phase II clinical study with 2000mg mesalamine (5-ASA) or placebo in LS patients for a 2-year treatment. 260 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 to receive 2000mg 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. Blood and stool samples will be collected for analysis of microbiota, ctDNA 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.
Tumor multiplicity and tumor progression (severity of the neoplastic lesions) will be investigated.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||260 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome|
|Actual Study Start Date :||March 21, 2022|
|Estimated Primary Completion Date :||October 15, 2028|
|Estimated Study Completion Date :||October 15, 2038|
Mesalamine (Mesalazine, Pentasa sachet, 5-ASA) 2 g once daily for 2 years.
The IMP will be supplied as sachets with slow-releasing granules.
Placebo Comparator: Placebo
Placebo for Mesalamine (Mesalazine, Pentasa sachet, 5-ASA) 2 g once daily for 2 years.
The IMP will be supplied as sachets with slow-releasing granules.
- Change in the occurrence of any colorectal neoplasia in LS patients [ Time Frame: End of treatment at 24 months +/- 1 month ]Occurrence of any colorectal neoplasia (both benign and malignant tumors) between groups is described by absolute frequencies and percentages.
- Change in the occurrence of any colorectal neoplasia in LS patients [ Time Frame: End of study at year 6 +/- 3 months. ]As above.
- Tumour multiplicity [ Time Frame: End of treatment at 24 months +/- 1 month ]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.
- Tumour progress [ Time Frame: End of treatment at 24 months +/- 1 month ]
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.
- Treatment effects [ Time Frame: End of treatment at 24 months +/- 1 month ]
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.
- Significant findings & illnesses - adverse events [ Time Frame: End of treatment at 24 months +/- 1 month ]
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||30 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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
- Regular use of aspirin/ASA: 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 incompetent to give an informed consent
- Pregnant or breastfeeding women
- Participation in another clinical study investigating another IMP within 1 month 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 and heart diseases) or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or ability to comply with study procedures, investigational product administration and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04920149
|Contact: Ann-Sofie Backman, MD PhD||707515285 ext firstname.lastname@example.org|
|Hvidovre Hospital||Not yet recruiting|
|Hvidovre, Denmark, 2650|
|Contact: Lone Sunde, MD PhD email@example.com|
|Principal Investigator: Lone Sunde, MD PhD|
|Dept. of Scientific Medicine and Surgery, University of Bologna||Not yet recruiting|
|Bologna, Emilia-Romagna, Italy, CAP 40138|
|Contact: Luigi Ricciardiello, MD PhD firstname.lastname@example.org|
|Principal Investigator: Luigi Ricciardiello, MD PhD|
|Department of Genetics and Pathomorphology of Pomeranian Medical University||Not yet recruiting|
|Szczecin, Poland, 71-252|
|Contact: Jan Lubinski, MD PhD email@example.com|
|Principal Investigator: Jan Lubinski, MD PhD|
|Sahlgrenska University Hsospital||Not yet recruiting|
|Göteborg, Gothenburg, Sweden, 416 85|
|Contact: David Ljungman, MD PhD firstname.lastname@example.org|
|Principal Investigator: David Ljungman, MD PhD|
|Skåne University Hospital||Not yet recruiting|
|Malmö, Skåne, Sweden, 205 02|
|Contact: Irene Stenfors, MD email@example.com|
|Principal Investigator: Irene Stenfors, MD|
|Karolinska University Hospital||Recruiting|
|Stockholm, Sweden, 171 76|
|Contact: Ann-Sofie Backman, MD PhD firstname.lastname@example.org|
|Principal Investigator: Ann-Sofie Backman, MD PhD|
|Norrland University Hospital||Not yet recruiting|
|Umeå, Sweden, 901 85|
|Contact: Gustav Silander, MD PhD email@example.com|
|Principal Investigator: Gustav Silander, MD PhD|
|Akademiska hospital||Not yet recruiting|
|Uppsala, Sweden, 751 85|
|Contact: Joakim Folkesson, MD PhD firstname.lastname@example.org|
|Principal Investigator: Joakim Folkesson, MD PhD|
|Principal Investigator:||Ann-Sofie Backman, MD PhD||Karolinska University Hospital|
|Responsible Party:||Ann-Sofie Backman, Consultant gastroenterology, Karolinska University Hospital|
|Other Study ID Numbers:||
|First Posted:||June 9, 2021 Key Record Dates|
|Last Update Posted:||March 28, 2022|
|Last Verified:||March 2022|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Colorectal Neoplasms, Hereditary Nonpolyposis
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Anti-Inflammatory Agents, Non-Steroidal
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs