Inositol in Preventing Colorectal Cancer in Patients With Colitis-Associated Dysplasia

Colon Carcinoma Clinical Trial

Official title:

Myo-Inositol Chemoprevention in Colitis-Associated Dysplasia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01111292
• Other study ID #: NCI-2011-01434
• Secondary ID: NCI-2011-01434CD
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: April 24, 2010
• Last updated: April 6, 2015
• Start date: October 2010

Study information

• Verified date: February 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This pilot, randomized phase I/II trial studies how well inositol works in preventing colorectal cancer in patients with abnormal cells (dysplasia) associated with inflammation of the colon (colitis). Patients with colitis-associated dysplasia may have an increased risk of developing colorectal cancer. Inositol is a vitamin-like substance that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the effect of myo-inositol (inositol), administered for 3 months, on phospho (P)-beta (B)-catenin staining in areas of low-grade dysplasia or in areas of prior low grade dysplasia in subjects with known colitis-induced low grade dysplasia at baseline.

SECONDARY OBJECTIVES:

I. To examine the effect of myo-inositol on regression of dysplasia. II. To examine the effect of inositol on p53 and Ki67 staining within remaining dysplasia.

III. To examine the effect of inositol on epithelial apoptosis (cleaved caspase-3) within dysplasia.

IV. To examine the effect of inositol on reductions in mucosal messenger ribonucleic acid (mRNA) levels of monocyte chemotactic protein 1 (MCP1), inducible nitric oxide synthase (iNOS), and cyclooxygenase (Cox)-2.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Beginning within 14 days after colonoscopy, patients receive inositol orally (PO) once daily (QD) on days 1-14 and twice daily (BID) on days 15-90.

ARM II: Beginning within 14 days after colonoscopy, patients receive placebo PO QD on days 1-14 and BID on days 15-90.

After completion of treatment, patients undergo biopsy and colonoscopy with or without mucosal resection.

After completion of study treatment, patients are followed up at 2 weeks.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must have ulcerative colitis or Crohn's disease with low grade dysplasia or polyploid dysplasia or have a history of dysplasia and increased positive beta-catenin levels confirmed by a consensus of the study pathologists (2 of 2, or 2 of 3)

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Absolute neutrophil count (ANC) > 1,500/uL

• Platelets > 100,000/uL

• Total bilirubin within normal institutional limits

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT] =< 1.5 times upper limit of normal

• Creatinine within normal institutional limits

• International normalized ratio (INR) < 1.5

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of baseline pregnancy test, throughout the duration of the study, and for 1 month following cessation of study drug; females must begin adequate contraception immediately following screening pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately; if she is pregnant, she will be immediately withdrawn from the study and followed until the birth of the child

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Subjects with life-threatening medical conditions that would preclude study treatment intervention and colonoscopy

• Participants may not be receiving any other investigational agents

• History of allergic reactions to rice or compounds of similar chemical or biologic composition to myo-inositol (i.e., urticaria, dermatologic reaction)

• Use of medications known to elevate serum blood glucose; participants on steroids are still eligible, as they will be monitored weekly for fasting blood glucose

• Participants with dysplasia-associated lesion or mass (DALM), high-grade dysplasia or invasive colonic carcinoma are excluded

• Uncontrolled intercurrent illness including, but not limited to

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Chronic renal failure

• Chronic renal insufficiency

• Psychiatric illness or social situations that would limit compliance with study requirements

• Prior treatment with myo-inositol

• History of systemic chemotherapy within 18 months of screening

• Subjects taking valproic acid and/or lithium

• Diabetes mellitus

• History of total proctocolectomy

• Concomitant primary sclerosing cholangitis (PSC)

• Pregnant or lactating subjects are excluded

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Carcinoma
• Colitis
• Colitis, Ulcerative
• Colon Carcinoma
• Crohn Disease
• Dysplasia in Crohn Disease
• Low Grade Dysplasia in Ulcerative Colitis
• Rectal Carcinoma

Intervention

Drug:
• Inositol
Given PO

Other:
• Placebo
Given PO
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Mount Sinai Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in P-ß-catenin staining within areas of dysplasia as measured by immunohistochemistry from samples obtained before and after study treatment	P-beta-catenin staining will be measured as percent of positive cells = counted # positively stained cells/total # cells present in the sample under consideration.	Baseline to 90 days	No
Secondary	Incidence of dysplasia in previously marked areas	The effects on disappearance of dysplasia in colonic biopsies will be determined as a pathological diagnosis rendered by two out of three study pathologists.	Day 90	No
Secondary	Change in p53 staining within dysplasia or in segments with prior dysplasia	Descriptive analysis will be provided.	Baseline to day 90	No
Secondary	Change in Ki67 staining within dysplasia or in segments with prior dysplasia	Descriptive analysis will be provided.	Baseline to day 90	No
Secondary	Change in mucosal apoptosis (cleaved caspase-3) within dysplasia or in segments with prior dysplasia	Descriptive analysis will be provided.	Baseline to day 90	No
Secondary	Change in mucosal mRNA levels of MCP-1 as determined by real time polymerase chain reaction (PCR)	Descriptive analysis will be provided.	Baseline up to 90 days	No
Secondary	Change in mucosal mRNA levels of iNOS as determined by real time PCR	Descriptive analysis will be provided.	Baseline up to 90 days	No
Secondary	Change in mucosal mRNA levels of Cox-2 as determined by real time PCR	Descriptive analysis will be provided.	Baseline up to 90 days	No
Secondary	Adverse events in study treatment	Identify the adverse event using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.	Up to 2 weeks post-treatment	Yes