Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

NCT ID: NCT04920149

Last Updated: 2024-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-21

Study Completion Date

2045-09-30

Brief Summary

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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

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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.

Conditions

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Lynch Syndrome Colon Cancer Colon Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Mesalamine

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

Group Type EXPERIMENTAL

Mesalamine

Intervention Type DRUG

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Mesalamine

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Mesalazine Pentasa sachet 5-ASA

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Swedish Research Council

OTHER_GOV

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role collaborator

Ann-Sofie Backman

OTHER

Sponsor Role lead

Responsible Party

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Ann-Sofie Backman

Consultant gastroenterology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ann-Sofie Backman, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Aalborg University Hospital

Aalborg, , Denmark

Site Status NOT_YET_RECRUITING

Hvidovre Hospital

Hvidovre, , Denmark

Site Status RECRUITING

Sahlgrenska University Hsospital

Gothenburg, Gothenburg, Sweden

Site Status RECRUITING

Skåne University Hospital

Malmo, Skåne County, Sweden

Site Status RECRUITING

Ersta Hospital/Ersta Diakoni

Stockholm, , Sweden

Site Status RECRUITING

Karolinska University Hospital

Stockholm, , Sweden

Site Status ACTIVE_NOT_RECRUITING

Norrland University Hospital

Umeå, , Sweden

Site Status RECRUITING

Akademiska hospital

Uppsala, , Sweden

Site Status NOT_YET_RECRUITING

Countries

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Italy Poland Denmark Sweden

Central Contacts

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Ann-Sofie Backman, MD PhD

Role: CONTACT

Phone: 707515285

Email: [email protected]

Facility Contacts

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Ole Thorlacius-Ussing, MD PhD

Role: primary

Lars Joachim Lindberg, MD PhD

Role: primary

David Ljungman, MD PhD

Role: primary

Rita J Gustafsson, MD PhD

Role: primary

Ann-Sofie Backman, MD PhD

Role: primary

Gustav Silander, MD PhD

Role: primary

Peter Thelin Schmidt, MD PhD

Role: primary

Other Identifiers

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MesaCAPP

Identifier Type: -

Identifier Source: org_study_id