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

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

Tracking Information

• First Submitted Date: May 30, 2006
• First Posted Date: May 31, 2006
• Last Update Posted Date: February 9, 2009
• Study Start Date: July 2006
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (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: Not Provided

Current Secondary Outcome Measures (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: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nitric Oxide-Releasing Acetylsalicyclic Acid in Preventing Colorectal Cancer in Patients at High Risk of Colorectal Cancer
• Official Title: 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Masking: Double; Primary Purpose: Prevention
• Condition: Colorectal Cancer

Intervention

• Drug: nitric oxide-releasing acetylsalicylic acid derivative
• Other: laboratory biomarker analysis
• Procedure: biopsy

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: November 8, 2006): 240
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00331786
• Other Study ID Numbers: CDR0000473094; SUNY-UH-20055574
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Stony Brook University
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Basil Rigas, MD; Stony Brook University

• PRS Account: National Cancer Institute (NCI)
• Verification Date: May 2007