Phase I Multiple-Dose Safety, Pharmacokinetic and Pharmacodynamic Clinical Study of Nitric Oxide Releasing Aspirin (NCX 4016)
50 Years
N/A
Both
Colorectal Cancer
Trial Information
Phase I Multiple-Dose Safety, Pharmacokinetic and Pharmacodynamic Clinical Study of Nitric Oxide Releasing Aspirin (NCX 4016)
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- At risk for colorectal cancer
- History of histologically proven sporadic colon adenomas or colon cancer
- At least 5 aberrant cryptic foci on sigmoidoscopy
- Less than 20 prior cumulative adenomas and no heredity nonpolyposis colorectal
cancer
- No significant asymptomatic lesions on sigmoidoscopy, including any of the following:
- Inflammation
- Strictures
- Anorectal lesions
- Fistulae
- Vascular lesions
- No adenomas or colon carcinomas on flexible sigmoidoscopy
- No history of gastrointestinal (GI) cancer other than colorectal cancer
- No inherited colorectal cancer syndromes
PATIENT CHARACTERISTICS:
- No other GI mucosal epithelial diseases (e.g., Barrett's esophagus, chronic or
recurrent peptic ulcer disease, celiac sprue, or other disorders of nutrient
absorption)
- No active peptic ulcer disease
- No history of inflammatory bowel disease (ulcerative colitis or Crohn's disease)
- No known or suspected alcohol ( > 5 glasses of wine or beer per day), drug, or
medication abuse
- No quantitative or qualitative platelet or coagulation abnormalities
- No personal or family history of a bleeding disorder
- No uncontrolled diabetes
- No uncontrolled hypertension, or chronic congestive heart failure (New York Heart
Association class II-IV heart disease)
- No myocardial infarction, transient ischemic attack, or stroke within the past 6
months
- No equilibrium disorders affecting gait or ability to stand that would preclude study
participation
- No involuntary change in weight (up or down) of ≥ 15% of usual body weight within the
past year
- Creatinine ≤ 2.0 mg/dL
- No chronic liver disease or pancreatitis
- No allergies to aspirin
- No prior severe adverse reactions to NSAIDs such as asthma, GI bleeding, or renal
insufficiency
- No institutionalized, mentally disabled patients
- No prisoners
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
- No concurrent antibiotic prophylaxis
- More than 7 days since prior nonsteroidal anti-inflammatory drug (NSAID) treatment,
including aspirin
- No concurrent frequent use (> 7 days in previous month) of NSAIDs, cyclooxygenase
(COX)-2 inhibitors, nitrovasodilators, or oral corticosteroids
- No concurrent macronutrient consumption below the 1st or above the 99th percentile of
U.S. consumption
- No concurrent anticoagulants, ticlopidine, and clopidogrel
- More than 3 months since prior general anesthesia
- More than 3 months since prior investigational agents
- No concurrent NSAIDs, including aspirin or COX-2 inhibitors
- Acetaminophen allowed
- No concurrent nitrovasodilating drugs
- More than 3 months since prior participation in other investigational trials
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Outcome Measure:
Effects of nitric oxide-releasing acetylsalicyclic acid (NCX 4016) on aberrant cryptic foci (ACF) multiplicity after the second dose at 6 months
Safety Issue:
No
Principal Investigator
Basil Rigas, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Stony Brook University
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000473094
NCT ID:
NCT00331786
Start Date:
July 2006
Completion Date:
Related Keywords:
- Colorectal Cancer
- colon cancer
- rectal cancer
- Colorectal Neoplasms
Name | Location |
|---|---|
| Stony Brook University Cancer Center | Stony Brook, New York 11794-8174 |
