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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01111292
First received: April 24, 2010
Last updated: September 16, 2014
Last verified: August 2014

April 24, 2010
September 16, 2014
October 2010
September 2014   (final data collection date for primary outcome measure)
Change in P-β-catenin staining within areas of dysplasia as measured by immunohistochemistry from samples obtained before and after study treatment [ Time Frame: Baseline to 90 days ] [ Designated as safety issue: No ]
P-beta-catenin staining will be measured as percent of positive cells = counted # positively stained cells/total # cells present in the sample under consideration.
Reduction in P-β-catenin staining within areas of dysplasia as measured by IHC from samples obtained before and after study treatment [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01111292 on ClinicalTrials.gov Archive Site
  • Disappearance of dysplasia in previously marked areas [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
    The effects on disappearance of dysplasia in colonic biopsies will be determined as a pathological diagnosis rendered by two out of three study pathologists.
  • Reduction in p53 staining within dysplasia or in segments with prior dysplasia [ Time Frame: Baseline to day 90 ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.
  • Reduction in Ki67 staining within dysplasia or in segments with prior dysplasia [ Time Frame: Baseline to day 90 ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.
  • Reduction in mucosal apoptosis (cleaved caspase-3) within dysplasia or in segments with prior dysplasia [ Time Frame: Baseline to day 90 ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.
  • Reduction of mucosal mRNA levels of MCP-1 as determined by real time polymerase chain reaction (PCR) [ Time Frame: Baseline up to 90 days ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.
  • Reductions in mucosal mRNA levels of iNOS as determined by real time PCR [ Time Frame: Baseline up to 90 days ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.
  • Reductions in mucosal mRNA levels of Cox-2 as determined by real time PCR [ Time Frame: Baseline up to 90 days ] [ Designated as safety issue: No ]
    Descriptive analysis will be provided.
  • Adverse events in study treatment [ Time Frame: Up to 2 weeks post-treatment ] [ Designated as safety issue: Yes ]
    Identify the adverse event using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
  • Disappearance of dysplasia in previously marked areas [ Designated as safety issue: No ]
  • p53 and Ki67 staining within dysplasia [ Designated as safety issue: No ]
  • Mucosal apoptosis (cleaved caspase-3) within dysplasia [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Inositol in Preventing Colorectal Cancer in Patients With Colitis-Associated Dysplasia
Myo-Inositol Chemoprevention in Colitis-Associated Dysplasia

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Colon Cancer
  • Crohn Disease-associated Dysplasia
  • Rectal Cancer
  • Ulcerative Colitis-associated Low-grade Dysplasia
  • Drug: inositol
    Given PO
    Other Name: myo-inositol
  • Other: placebo
    Given PO
    Other Name: PLCB
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm I (inositol)
    Beginning within 14 days after colonoscopy, patients receive inositol PO QD on days 1-14 and BID on days 15-90.
    Interventions:
    • Drug: inositol
    • Other: laboratory biomarker analysis
  • Placebo Comparator: Arm II (placebo)
    Beginning within 14 days after colonoscopy, patients receive placebo PO QD on days 1-14 and BID on days 15-90.
    Interventions:
    • Other: placebo
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
20
Not Provided
September 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01111292
NCI-2011-01434, NCI-2011-01434, CDR0000671302, NCI09-13-02, NWU09-13-02, N01CN35157, P30CA060553
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Terrence Barrett Northwestern University
National Cancer Institute (NCI)
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP