Nitric Oxide-Releasing Acetylsalicyclic Acid in Preventing Colorectal Cancer in Patients at High Risk of Colorectal Cancer

This study has been completed.
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: May 30, 2006
Last updated: February 6, 2009
Last verified: May 2007

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.

Condition Intervention Phase
Colorectal Cancer
Drug: nitric oxide-releasing acetylsalicylic acid derivative
Other: laboratory biomarker analysis
Procedure: biopsy
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Phase I Multiple-Dose Safety, Pharmacokinetic and Pharmacodynamic Clinical Study of Nitric Oxide Releasing Aspirin (NCX 4016)

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

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 ]

Estimated Enrollment: 240
Study Start Date: July 2006
Detailed Description:



  • 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.


Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
  Contacts and Locations
Please refer to this study by its identifier: NCT00331786

United States, New York
Stony Brook University Cancer Center
Stony Brook, New York, United States, 11794-8174
Sponsors and Collaborators
Stony Brook University
Principal Investigator: Basil Rigas, MD Stony Brook University
  More Information

Additional Information:
No publications provided Identifier: NCT00331786     History of Changes
Other Study ID Numbers: CDR0000473094, SUNY-UH-20055574
Study First Received: May 30, 2006
Last Updated: February 6, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
colon cancer
rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Nitric Oxide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors processed this record on April 21, 2014