Nitric Oxide-Releasing Acetylsalicyclic Acid in Preventing Colorectal Cancer in Patients at High Risk of Colorectal Cancer
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of nitric oxide-releasing acetylsalicyclic acid may prevent colorectal cancer.
PURPOSE: This randomized phase I trial is studying the side effects and best dose of nitric oxide-releasing acetylsalicyclic acid in preventing colorectal cancer in patients at high risk of colorectal cancer.
Drug: nitric oxide-releasing acetylsalicylic acid derivative
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Primary Purpose: Prevention
|Official Title:||Phase I Multiple-Dose Safety, Pharmacokinetic and Pharmacodynamic Clinical Study of Nitric Oxide Releasing Aspirin (NCX 4016)|
- 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 ]
- 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 ]
|Study Start Date:||July 2006|
- Evaluate the effects of nitric oxide-releasing acetylsalicyclic acid on aberrant cryptic foci (ACF) in patients at high risk for colon cancer.
- 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.
|United States, New York|
|Stony Brook University Cancer Center|
|Stony Brook, New York, United States, 11794-8174|
|Principal Investigator:||Basil Rigas, MD||Stony Brook University|