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

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ClinicalTrials.gov Identifier: NCT00331786
Recruitment Status : Completed
First Posted : May 31, 2006
Last Update Posted : February 9, 2009
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE May 30, 2006
First Posted Date  ICMJE May 31, 2006
Last Update Posted Date February 9, 2009
Study Start Date  ICMJE July 2006
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
Effects of nitric oxide-releasing acetylsalicyclic acid (NCX 4016) on aberrant cryptic foci (ACF) multiplicity after the second dose at 6 months
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
  • Pharmacokinetic profile by blood, urine, and colon tissue sampling
  • Incidence of ACF as measured by magnification chromoendoscopy
  • 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
  • Data on C-Reactive protein as a marker for inflammation
  • Safety and tolerability of long-term oral administration of NCX 4016 as measured by NCI CTCAE v3.0
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nitric Oxide-Releasing Acetylsalicyclic Acid in Preventing Colorectal Cancer in Patients at High Risk of Colorectal Cancer
Official Title  ICMJE Phase I Multiple-Dose Safety, Pharmacokinetic and Pharmacodynamic Clinical Study of Nitric Oxide Releasing Aspirin (NCX 4016)
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Masking: Double
Primary Purpose: Prevention
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: nitric oxide-releasing acetylsalicylic acid derivative
  • Other: laboratory biomarker analysis
  • Procedure: biopsy
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
240
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00331786
Other Study ID Numbers  ICMJE CDR0000473094
SUNY-UH-20055574
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Stony Brook University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Basil Rigas, MD Stony Brook University
PRS Account National Cancer Institute (NCI)
Verification Date May 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP