Spectral Markers in Aspirin Chemoprevention of Colonic Neoplasia
Spectral Markers in Aspirin Chemoprevention of Colonic Neoplasia
This randomized phase II trial is studying how well aspirin works in preventing colorectal cancer in patients at increased risk of colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of aspirin may prevent colorectal cancer.
PRIMARY OBJECTIVE:
I. 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 OBJECTIVES:
I. Assess the effect of this drug on colonic epithelial apoptosis and cell proliferation in these patients.
II. Assess the effect of this drug on rectal prostaglandin levels in these patients.
III. Assess the effect of this drug on platelet cyclooxygenase activity in these patients.
IV. 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.
Criteria:
No active or metastatic cancer within the past 6 months
Scheduled to undergo colonoscopy for colonic neoplasia surveillance
Hemoglobin >= 12.0 g/dL
Platelet count >= 120,000/mm^3
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
History of significant colonic neoplasia, defined as 1 of the following:
INR =< 1.5
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