Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Mesalamine

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Mesalazine, 3 grams once daily for six months

Placebo, 3 grams, once daily for six months

Mesalazine 3 grams, once daily for six months

Mesalazine

Placebo 3 grams, once daily for six months

Placebo

Several studies indicate that mesalazine might have a preventive effect on recurrence of adenomas in patients with and without inflammatory bowel disease. As mesalazine has limited adverse effects, it is an attractive candidate for chemoprevention. In this study we aim to investigate the antineoplastic properties of mesalazine in patients with sporadic colorectal adenomas.

Rationale: Patients with sporadic colorectal adenomatous polyps removed by polypectomy have a high rate of polyp recurrence and carry an increased risk for the development of colorectal carcinoma (CRC). Chemoprevention may lower the rate of adenoma recurrence after polypectomy, thereby reducing the risk of development or death from CRC. Mesalazine is an attractive candidate for chemoprevention, since even during long-term use it has only limited systemic adverse effects and no gastrointestinal toxicity. In a prospective trial a trend towards reduced adenoma recurrence has been observed in high risk patients with a history of at least 3 sporadic colorectal adenomas treated with mesalazine. Identification of biologically relevant antineoplastic properties of mesalazine in patients with sporadic adenomatous polyps will support further investigation of mesalazine as chemopreventive agent against colorectal neoplasia in the sporadic setting. Growth inhibition of colonic epithelial cells through induction of apoptosis and inhibition of proliferation is widely recognized as a potential mechanism for chemoprevention of colorectal cancer. In vivo data suggest that mesalazine exerts pro-apoptotic and anti-proliferative effects on normal colorectal epithelial cells. Furthermore, there is in vitro evidence in CRC cells that mesalazine inhibits Wnt/beta-catenin signalling, an early and common inappropriately activated pathway in colorectal carcinogenesis and molecular target for chemoprevention.

Objective: Evaluate the effects of mesalazine therapy on histologically normal sigmoid and rectal mucosa in patients at high risk of recurrent sporadic colorectal adenomas.

Primary endpoints:

* change in apoptotic index after treatment as compared to placebo
* change in proliferation index and distribution of proliferating cells in crypts after treatment as compared to placebo

Secondary endpoint:

• change in expression of beta-catenin signaling pathway components after treatment as compared to placebo

Study design: double-blind, randomized placebo-controlled study

Study population: 68 patients, aged 50-75 years, who underwent polypectomy within 6 months before study entry, for removal of 2 or more colorectal adenomas irrespective of size and/or 1 colorectal adenoma with at least 1 of the following features: a diameter of at least 1 cm at endoscopy, a proximal localization, high-grade dysplasia or villous histology.

Intervention: Patients will be randomized to receive 3.0 g mesalazine (n=34) or placebo (n=34) once daily for 6 months in a double-blinded way. At baseline and after 6 months of treatment, a sigmoidoscopy will be performed and five biopsies of normal appearing sigmoid and rectal mucosa will be collected.

Main study parameters/endpoints: The effect of treatment with mesalazine on apoptotic and proliferation indices relative to the placebo group.

Mesalazine Effects in Sporadic Colorectal Adenoma Patients

Chemopreventive Effects of Mesalazine in Patients at High Risk of Recurrent (Nonfamilial) Colorectal Adenomas

Change in apoptotic index after treatment with mesalazine as compared to placebo

Change in proliferation index and distribution of proliferating cells in crypts after treatment with mesalazine as compared to placebo

Change in expression of β-catenin signaling pathway components after treatment with mesalazine as compared to placebo

UMC Utrecht

Prof. dr. (MD, PhD) P.D. Siersema

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Anti-Infective Agents

Herbal and Botanical

Aminosalicylic Acid

Antitubercular Agents

Anti-Bacterial Agents

Cola

Mesalazine 800 mg orally t.i.d for 3 months

Mesalazine cpr 800 mg t.i.d. for 3 months

Federico Buffoli, Doctor

The purpose of this study is to obtain an "in vivo" confirmation that mesalazine induces the gene expression of μ-protocadherin and other related genes in the colon mucosa, as demonstrated in some "in vitro" experiments. .

Pilot Trial, single-blind, parallel group on biopsy specimens of healthy colon mucosa in patients with precancerous lesions of the colon and rectum (adenomas) treated with mesalazine.

Chemopreventive Action of Mesalazine on Colorectal Cancer: a Pilot Study for an "in Vivo" Evaluation of the Molecular Effects on β-catenin Signaling Pathway.

Azione Chemiopreventiva Della Mesalazina Sul Cancro Del Colon-retto: Studio Pilota Per la Valutazione Degli Effetti Molecolari "in Vivo" Sulla Via di Segnalazione Proliferativa Della β-catenina (Official Title in Italian Language)

Molecular analysis (quantitative RT-PCR) of gene expression levels of μ-protocadherin, protocadherin 19, protocadherin 24, cadherin E, TCF7L2, TCF4, c-myc, Cyclin D1, p21waf1, VEGF, CD44, Met, KLF4 e CEBP-α and comparison of the levels assessed at the end of the treatment period with the baseline.

These parameters will be examined using molecular analysis of the oxidation and depurination levels of the DNA and chromatographic analysis of the intra-mucosal concentration of 5-Acetylsalicylic acid, in biopsies of normal mucosa of the colon taken before and after the treatment of patients with 5-Acetylsalicylic acid:

* quantification of the percentage of cells expressing the following proteins by immunohistochemical analysis: μ-protocadherin, Ki-67, Caspase-3 and Histone H2AXγ;
* quantification of number of AP sites per 100000 DNA bp
* quantification of nanograms di 8-OhdG (8-hydroxyguanine) per micrograms of DNA

SOFAR S.p.A.

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Syndrome

Colorectal Neoplasms, Hereditary Nonpolyposis

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

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

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

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

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.

mesalamine 2400 MG (5-ASA)

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.

mesalamine 1200 MG

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.

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.

This is a multicenter, multinational, randomized, 3-arm, double-blind, phase II clinical study with 2400mg mesalamine (5-ASA), 1200mg mesalamine (5-ASA) or placebo in LS patients for a 2-year treatment. 540 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 1:1:1 (180 each) to receive 2400mg mesalamine, 1200mg 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. A serum and stool sample will be taken to identify for mesalamine compliance 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.

A 50% reduction of the occurrence of colorectal neoplasia in mesalamine-treated patients is expected. Tumor multiplicity and tumor progression (severity of the neoplastic lesions) will be investigated.

Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome

Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome - MesaCAPP

• 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.

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.

All tests are two-sided and a significance level of 5 % is used.

The tumor progress in 4 ordered stages will be tested between groups by a chi-square trend test stratified for country and history of cancer before randomization and modelled by an ordinal logistic regression.

It will be tested whether 5-ASA (low- and high-dose together) 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.

All tests are two-sided and a significance level of 5 % is used.

The dependence of treatment effects on history of colorectal cancer, sex and patients age (\<45 years and ≥45 years) will be assessed by modelling interactions between these factors and treatment in the corresponding regression models.

If differences between 5-ASA (low- and high-dose together) 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 (LS patients below 45 years of age or 45 years of age and older) will be investigated.

All tests are two-sided and a significance level of 5 % is used.

Differences between high and low dose ASA for the occurrence of colorectal neoplasia, tumor multiplicity and tumor progression will be analysed by the same methods as for the comparison between ASA and placebo to investigate differences between low and high dose 5-ASA with respect to the occurrence of colorectal neoplasia, to tumor multiplicity and tumor progression.

All tests are two-sided and a significance level of 5 % is used.

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.

All tests are two-sided and a significance level of 5 % is used.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Mesalazine Effects in Sporadic Colorectal Adenoma Patients	NCT01894685	Sporadic Colore...	Mesalazine Placebo	50 Years - 75 Years	UMC Utrecht
Chemopreventive Action of Mesalazine on Colorectal Cancer: a Pilot Study for an "in Vivo" Evaluation of the Molecular Effects on β-catenin Signaling Pathway.	NCT02077777	Colorectal Canc...	Mesalazine	18 Years -	SOFAR S.p.A.
Chemopreventive Action of Mesalazine on Colorectal Cancer: a Pilot Study for an "in Vivo" Evaluation of the Molecular Effects on β-catenin Signaling Pathway.	NCT02077777	Colorectal Canc...	Mesalazine	18 Years -	SOFAR S.p.A.
Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome	NCT03070574	Colorectal Canc...	mesalamine 2400... mesalamine 1200... Placebo	25 Years -	Medical University of Vienna

Spots Global Cancer Trial Database for mesalazine

Every month we try and update this database with for mesalazine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mesalazine

Every month we try and update this database with for mesalazine cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mesalazine cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.