Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer - Full Text View

Sponsors and Collaborators:	Robert H. Lurie Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00468910

Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of aspirin may prevent colorectal cancer.

PURPOSE: This randomized phase II trial is studying how well aspirin works in preventing colorectal cancer in patients at increased risk of colorectal cancer.

Condition	Intervention	Phase
Colorectal Cancer Precancerous/Nonmalignant Condition	Drug: acetylsalicylic acid Procedure: biopsy Procedure: immunoenzyme technique Procedure: immunohistochemistry staining method Procedure: laboratory biomarker analysis Procedure: light-scattering spectroscopy Procedure: polymerase chain reaction Procedure: polymorphism analysis	Phase I

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Acetylsalicylic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Placebo Control
Official Title:	Spectral Markers In Aspirin Chemoprevention of Colonic Neoplasia

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

Primary Outcome Measures:

Observed change in spectral slope and fractal dimension from baseline [ Designated as safety issue: No ]
Reversal of neoplastic micro-architectural changes by acetylsalicylic acid (aspirin) as assessed by 4D-ELF parameters [ Designated as safety issue: No ]

Secondary Outcome Measures:

Colonic epithelial apoptosis and cell proliferation as measured by immunohistochemical detection of cleaved caspase 3 and Ki-67 expression [ Designated as safety issue: No ]
Rectal prostaglandin levels as measured by ELISA [ Designated as safety issue: No ]
Platelet cyclooxygenase (COX) activity as measured by a peroxidase-based COX enzyme activity assay [ Designated as safety issue: No ]
Correlation of spectral marker alterations with UGT1A6 genotype [ Designated as safety issue: No ]
Rectal apoptosis [ Designated as safety issue: No ]
Rectal proliferation [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	March 2007
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine whether acetylsalicylic acid (aspirin) will alter spectral markers (i.e., spectral slope and fractal dimension) in distal colonic mucosa of patients who are at increased risk for the development or recurrence of colorectal cancer.

Secondary

Assess the effect of this drug on colonic epithelial apoptosis and cell proliferation in these patients.
Assess the effect of this drug on rectal prostaglandin levels in these patients.
Assess the effect of this drug on platelet cyclooxygenase activity in these patients.
Correlate changes in spectral markers with UGT1A6 genotype in patients treated with this drug.

OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled study. Patients are stratified by clinical site and adenoma/carcinoma maximal size. Patients with abnormal spectral biomarkers are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral acetylsalicylic acid (aspirin) once daily.
Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for 3 months in the absence of unacceptable toxicity.

Patients undergo flexible sigmoidoscopy and biopsies as well as blood collection at baseline (during prestudy colonoscopy) and at completion of study treatment for comparison of spectral signatures with biomarkers of both aspirin activity (including plasma cyclooxygenase activity and rectal prostaglandin levels) as well as with biomarkers associated with antineoplastic alteration (including apoptosis and cell proliferation). UGT1A6 genotyping analysis is also performed.

After completion of study treatment, patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 115 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

History of significant colonic neoplasia, defined as 1 of the following:
- Adenoma within the past 6 years
- Colorectal cancer within the past 6 years
- Known adenoma on present exam OR histologically confirmed polyps seen on imaging
No active or metastatic cancer within the past 6 months
Scheduled to undergo colonoscopy for colonic neoplasia surveillance

PATIENT CHARACTERISTICS:

Hemoglobin ≥ 12.0 g/dL
Platelet count ≥ 120,000/mm³
INR ≤ 1.5
AST or ALT ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 1.5 times ULN
Bilirubin ≤ 1.5 times ULN
BUN ≤ 40 mg/dL
Glomerular filtration rate ≥ 45 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No coagulopathy
No anemia
No history of peptic ulcer disease or gastrointestinal hemorrhage
No history of cerebrovascular accident
No uncontrolled hypertension
No history of intolerance or allergy to aspirin or to NSAIDs
No liver disease as manifested by signs or symptoms of cirrhosis
No endoscopic or radiographic evidence of portal hypertension
No active colitis by endoscopy
No history of inflammatory bowel disease
No requirement for aspirin as medical therapy (i.e., post-myocardial infarction or transient ischemic attack)
No untreated helicobacter pylori infection

PRIOR CONCURRENT THERAPY:

At least 6 months since prior cancer treatment
No other concurrent acetylsalicylic acid (aspirin)-containing products or non-steroidal anti-inflammatory drugs (NSAIDs)
No concurrent systemic corticosteroids
No other concurrent anticoagulants or antiplatelet agents
No concurrent investigational drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468910

Locations

United States, Illinois
Evanston Northwestern Healthcare - Evanston Hospital	Recruiting
Evanston, Illinois, United States, 60201-1781
Contact: Clinical Trials Office - Evanston Northwestern Healthcare - Ev 847-570-1381
Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Recruiting
Chicago, Illinois, United States, 60611-3013
Contact: Clinical Trials Office - Robert H. Lurie Comprehensive Cancer 312-695-1301 cancer@northwestern.edu
University of Chicago Cancer Research Center	Recruiting
Chicago, Illinois, United States, 60637
Contact: David T. Rubin, MD 773-702-4708 drubin@uchicago.edu

Sponsors and Collaborators

Robert H. Lurie Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Raymond C. Bergan, MD

Robert H. Lurie Cancer Center

More Information

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

Study ID Numbers:	CDR0000540545, NU-NWU04-2-03
Study First Received:	May 2, 2007
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00468910
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

colon cancer
rectal cancer
precancerous/nonmalignant condition

Study placed in the following topic categories:

Digestive System Neoplasms
Precancerous Conditions
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

Intestinal Neoplasms
Rectal neoplasm
Digestive System Diseases
Aspirin
Gastrointestinal Neoplasms
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Hematologic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents
Neoplasms

Neoplasms by Site
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009