Primary Outcome Measures:
- Effects of nitric oxide-releasing acetylsalicyclic acid (NCX 4016) on aberrant cryptic foci (ACF) multiplicity after the second dose at 6 months [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Pharmacokinetic profile by blood, urine, and colon tissue sampling [ Designated as safety issue: No ]
- Incidence of ACF as measured by magnification chromoendoscopy [ Designated as safety issue: No ]
- Assessment of biomarkers expressed in colon tissue, including PGE2 (measured by immunoassay), COX-1, COX-2, NF-kB, and β-catenin (measured by immunohistochemistry) at baseline and at the final visit [ Designated as safety issue: No ]
- Data on C-Reactive protein as a marker for inflammation [ Designated as safety issue: No ]
- Safety and tolerability of long-term oral administration of NCX 4016 as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
OBJECTIVES:
Primary
- Evaluate the effects of nitric oxide-releasing acetylsalicyclic acid on aberrant cryptic foci (ACF) in patients at high risk for colon cancer.
Secondary
- Determine the pharmacokinetic profile of this drug in these patients.
- Determine the presence or absence of ACF in these patients.
- Determine the expression of PGE2, COX-1, COX-2, NF-kB, and β-catenin in colon tissue.
- Determine the safety and tolerability of long-term nitric oxide-releasing acetylsalicyclic acid in these patients.
OUTLINE: This is a multicenter, double-blind, randomized, placebo-controlled, parallel group study. Patients are stratified according to gender and race (black vs non-Hispanic white vs Hispanic white vs Asian). Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive oral nitric oxide-releasing acetylsalicyclic acid twice daily for 6 months.
- Arm II: Patients receive nitric oxide-releasing acetylsalicyclic acid twice daily for 6 months at a higher dose than in arm I.
- Arm III: Patients receive oral placebo twice daily for 6 months. Patients undergo sigmoidoscopies at baseline and at the completion of study treatment. Biopsies of aberrant cryptic foci (ACF) and non-ACF sites are collected at both sigmoidoscopies. Tissue is examined for biomarkers (PGE_2, COX, NF-kB, β-catenin).
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 240 patients will be accrued for this study.