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

PRIMARY OBJECTIVES:

I. To evaluate the effect of myo-inositol (inositol), administered for 3 months, on
P-β-catenin staining in areas of low-grade dysplasia or in areas of prior low grade
dysplasia in patients with colitis-induced low-grade dysplasia.

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 undergo biopsy and colonoscopy to confirm areas of discrete dysplasia.
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 by telephone at 2 weeks.

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/mm^3

- Platelets > 100,000/mm^3

- 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

- The safety of myo-inositol during pregnancy is unknown; therefore, pregnant or
lactating subjects are excluded