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Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome (MesaCAPP)

Primary Purpose

Lynch Syndrome, Colon Cancer, Colon Neoplasm

Status

Recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Mesalamine

Placebo

About this trial

This is an interventional prevention trial for Lynch Syndrome

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

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 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

Sites / Locations

Hvidovre Hospital
Dept. of Scientific Medicine and Surgery, University of Bologna
Department of Genetics and Pathomorphology of Pomeranian Medical University
Sahlgrenska University Hsospital
Skåne University Hospital
Karolinska University HospitalRecruiting
Norrland University Hospital
Akademiska hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Mesalamine

Placebo

Arm Description

Mesalamine (Mesalazine, Pentasa sachet, 5-ASA) 2 g once daily for 2 years.

Placebo for Mesalamine (Mesalazine, Pentasa sachet, 5-ASA) 2 g once daily for 2 years.

Outcomes

Primary Outcome Measures

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.

Change in the occurrence of any colorectal neoplasia in LS patients

As above.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT04920149

First Posted

June 3, 2021

Last Updated

March 25, 2022

Sponsor

Ann-Sofie Backman

Collaborators

The Swedish Research Council

1. Study Identification

Unique Protocol Identification Number

NCT04920149

Brief Title

Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

Acronym

MesaCAPP

Official Title

Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 21, 2022 (Actual)

Primary Completion Date

October 15, 2028 (Anticipated)

Study Completion Date

October 15, 2038 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Ann-Sofie Backman

Collaborators

The Swedish Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lynch Syndrome, Colon Cancer, Colon Neoplasm

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

260 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Mesalamine

Arm Type

Experimental

Arm Description

Mesalamine (Mesalazine, Pentasa sachet, 5-ASA) 2 g once daily for 2 years.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo for Mesalamine (Mesalazine, Pentasa sachet, 5-ASA) 2 g once daily for 2 years.

Intervention Type

Drug

Intervention Name(s)

Mesalamine

Other Intervention Name(s)

Mesalazine, Pentasa sachet, 5-ASA

Intervention Description

The IMP will be supplied as sachets with slow-releasing granules.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

The IMP will be supplied as sachets with slow-releasing granules.

Primary Outcome Measure Information:

Title

Change in the occurrence of any colorectal neoplasia in LS patients

Description

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 month

Title

Change in the occurrence of any colorectal neoplasia in LS patients

Description

As above.

Time Frame

End of study at year 6 +/- 3 months.

Secondary Outcome Measure Information:

Title

Tumour multiplicity

Description

Time Frame

End of treatment at 24 months +/- 1 month

Title

Tumour progress

Description

Time Frame

End of treatment at 24 months +/- 1 month

Title

Treatment effects

Description

Time Frame

End of treatment at 24 months +/- 1 month

Title

Significant findings & illnesses - adverse events

Description

Time Frame

End of treatment at 24 months +/- 1 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ann-Sofie Backman, MD PhD

Phone

707515285

Ext

ann-sofie.backman@sll.se

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ann-Sofie Backman, MD PhD

Organizational Affiliation

Karolinska University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hvidovre Hospital

City

Hvidovre

ZIP/Postal Code

2650

Country

Denmark

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lone Sunde, MD PhD

lone.sunde@gmail.com

First Name & Middle Initial & Last Name & Degree

Lone Sunde, MD PhD

Facility Name

Dept. of Scientific Medicine and Surgery, University of Bologna

City

Bologna

State/Province

Emilia-Romagna

ZIP/Postal Code

CAP 40138

Country

Italy

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Luigi Ricciardiello, MD PhD

luigi.ricciardiello@unibo.it

First Name & Middle Initial & Last Name & Degree

Luigi Ricciardiello, MD PhD

Facility Name

Department of Genetics and Pathomorphology of Pomeranian Medical University

City

Szczecin

ZIP/Postal Code

71-252

Country

Poland

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jan Lubinski, MD PhD

lubinski@pum.edu.pl

First Name & Middle Initial & Last Name & Degree

Jan Lubinski, MD PhD

Facility Name

Sahlgrenska University Hsospital

City

Göteborg

State/Province

Gothenburg

ZIP/Postal Code

416 85

Country

Sweden

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Ljungman, MD PhD

david.ljungman@vgregion.se

First Name & Middle Initial & Last Name & Degree

David Ljungman, MD PhD

Facility Name

Skåne University Hospital

City

Malmö

State/Province

Skåne

ZIP/Postal Code

205 02

Country

Sweden

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Irene Stenfors, MD

irene.stenfors@skane.se

First Name & Middle Initial & Last Name & Degree

Irene Stenfors, MD

Facility Name

Karolinska University Hospital

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ann-Sofie Backman, MD PhD

ann-sofie.backman@regionstockholm.se

First Name & Middle Initial & Last Name & Degree

Ann-Sofie Backman, MD PhD

Facility Name

Norrland University Hospital

City

Umeå

ZIP/Postal Code

901 85

Country

Sweden

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gustav Silander, MD PhD

gustav.silander@vll.se

First Name & Middle Initial & Last Name & Degree

Gustav Silander, MD PhD

Facility Name

Akademiska hospital

City

Uppsala

ZIP/Postal Code

751 85

Country

Sweden

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joakim Folkesson, MD PhD

joakim.folkesson@sursci.uu.se

First Name & Middle Initial & Last Name & Degree

Joakim Folkesson, MD PhD

12. IPD Sharing Statement

Learn more about this trial

Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

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