Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

NCT03070574 | Terminated Phase 2

• 1 other identifier: MesaCAPP
• Study Type: interventional
• Target: 8
• Locations: 6 countries
• Sites: 6

Brief Summary

Multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine, 1200mg mesalamine or placebo for prevention of colorectal neoplasia in Lynch Syndrome patients for 2 years.

Conditions

Colorectal Cancer

Keywords

Lynch Syndrome; Chemoprevention; Mesalazine; 5-ASA

Outcome Measures

Primary Outcomes (2)

• Reduction 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 with 95 % confidence intervals. A logistic regression is used to assess differences between active treatment and placebo for the occurrence of any colorectal neoplasia, adjusted for country and history of cancer before randomization. Treatment effects are assessed by odds-ratios and corresponding 95 % confidence intervals.

  End of treatment at 24 months +/- 1 month

• Reduction in the occurrence of any colorectal neoplasia in LS patients

  As above

  End of study at year 6 +/- 3 months

Secondary Outcomes (5)

• Tumor multiplicity

  End of treatment at 24 months +/- 1 month

• Tumor progress

  End of treatment at 24 months +/- 1 month

• Treatment effects

  End of treatment at 24 months +/- 1 month

• High and low dose ASA

  End of treatment at 24 months +/- 1 month

• Significant findings & illnesses - adverse events

  End of treatment at 24 months +/- 1 month

Study Arms (3)

2400 MG mesalamine (5-ASA) total

EXPERIMENTAL

2400mg (1200mg mesalamine/1200mg) mesalamine once daily in the morning for the treatment phase of the study (24 months)

Drug: mesalamine 2400 MG (5-ASA)

1200 MG mesalamine (5-ASA) total

EXPERIMENTAL

placebo/1200mg mesalamine once daily in the morning for the treatment phase of the study (24 months)

Drug: mesalamine 1200 MG; Other: Placebo

Placebo

PLACEBO COMPARATOR

placebo/placebo once daily in the morning for the treatment phase of the study (24 months)

Other: Placebo

Interventions

mesalamine 2400 MG (5-ASA) DRUG

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers, each 1200mg of IMP (= 2400 mg), every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Also known as: Mezavant, Mesalazine, 5-aminosalicylic acid (5-ASA)

2400 MG mesalamine (5-ASA) total

mesalamine 1200 MG DRUG

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (1200 mg/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

Also known as: Mezavant, Mesalazine, 5-aminosalicylic acid (5-ASA)

1200 MG mesalamine (5-ASA) total

Placebo OTHER

For this study IMP will be supplied as film-coated tablets packed in containers. Each patient will receive two different containers of IMP (placebo/placebo) every 3 months (± 1 week), 100 tablets per container. The containers will be marked in different colours, to prevent the patients from taking two tablets from one container accidentally.

1200 MG mesalamine (5-ASA) total; Placebo

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \> 25 years
• 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.

You may not qualify if:

• 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 colorectal cancer (CRC) are excluded
• Presence of 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
• Patients after total or subtotal 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 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 andefficacy or protocol adherence

Sponsors & Collaborators

• Christoph Gasche: lead
• Prof. Dr. Gabriela Möslein, Germany: collaborator
• Prof. Dr. Hans Vasen, The Netherlands: collaborator
• Prof. Dr. med. Jan Lubinski, Poland: collaborator
• Prof. Dr. med. Yaron Niv, Israel: collaborator
• Univ. Prof. Dr. Judith Karner-Hanusch, Austria: collaborator
• Ann-Sofie Backman, MD PhD, Sweden: collaborator

Study Sites (6)

Department of Surgery, Medical University Vienna

Vienna, 1090, Austria

Location

HELIOS Universitätsklinikum Wuppertal, Zentrum für Hereditäre Tumorerkrankungen

Wuppertal, North Rhine-Westphalia, 42883, Germany

Location

Rabin Medical Center Beilinson Hospital Gastroenterology Department

Petah Tikva, 4941492, Israel

Location

Leiden University Medical Center

Leiden, 2333ZA, Netherlands

Location

Department of Genetics and Pathomorphology of Pomeranian Medical University

Szczecin, 71-252, Poland

Location

Karolinska universitetsjukhuset, A6:00 Gastroenterologiskt öppenvårdscentrum, Mottagningen för ärftlig tarmcancer

Solna, 17176, Sweden

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis

Interventions

Mesalamine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Univ. Prof. Dr. Christoph Gasche - Coordinating Investigator

Study Record Dates

• First Submitted: February 22, 2017
• First Posted: March 3, 2017
• Study Start: November 24, 2017
• Primary Completion: April 10, 2019
• Study Completion: April 10, 2019
• Last Updated: April 18, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); AU (1); IL (1); PL (1); NL (1); SE (1)