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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00331786
First received: May 30, 2006
Last updated: February 6, 2009
Last verified: May 2007
  Purpose

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:

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00331786

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

Additional Information:
No publications provided

ClinicalTrials.gov 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
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Aspirin
Nitroaspirin
Nitric Oxide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
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

ClinicalTrials.gov processed this record on April 16, 2014