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

Sponsors and Collaborators:	Stony Brook University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00331786

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 I

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Acetylsalicylic acid Nitric oxide NCX 4016 NCX-4016

U.S. FDA Resources

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Basil Rigas, MD

Stony Brook University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000473094, SUNY-UH-20055574
Study First Received:	May 30, 2006
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00331786 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

colon cancer
rectal cancer

Study placed in the following topic categories:

Anti-Inflammatory Agents
Vasodilator Agents
Neurotransmitter Agents
Antioxidants
Gastrointestinal Diseases
Rectal Neoplasms
Colonic Diseases
Fibrinolytic Agents
Rectal Diseases
Nitroaspirin
Fibrin Modulating Agents
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Digestive System Neoplasms

Cyclooxygenase Inhibitors
Rectal Neoplasm
Anti-Asthmatic Agents
Cardiovascular Agents
Intestinal Diseases
Intestinal Neoplasms
Protease Inhibitors
Nitric Oxide
Rectal Cancer
Digestive System Diseases
Cysteine
Analgesics, Non-Narcotic
Gastrointestinal Neoplasms
Platelet Aggregation Inhibitors
Peripheral Nervous System Agents

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Respiratory System Agents
Vasodilator Agents
Neurotransmitter Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Hematologic Agents
Colonic Diseases
Physiological Effects of Drugs
Fibrinolytic Agents
Nitroaspirin
Rectal Diseases
Fibrin Modulating Agents
Neoplasms by Site

Aspirin
Sensory System Agents
Therapeutic Uses
Free Radical Scavengers
Endothelium-Dependent Relaxing Factors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Digestive System Neoplasms
Cyclooxygenase Inhibitors
Anti-Asthmatic Agents
Enzyme Inhibitors
Cardiovascular Agents
Intestinal Diseases
Protective Agents
Intestinal Neoplasms

ClinicalTrials.gov processed this record on July 06, 2009