Aspirin in Preventing Colorectal Cancer in Patients at Increased Risk of Colorectal Cancer

• Observed change in spectral slope and fractal dimension from baseline [ Time Frame: Six Rectum Biopsies will be performed during pre-study and month 3 ] [ Designated as safety issue: No ]
  Six Rectum Biopsies will be performed during pre-study and month 3 to observe change in spectral slope and fractal dimension.
  
  

• Colonic epithelial apoptosis and cell proliferation as measured by immunohistochemical detection of cleaved caspase 3 and Ki-67 expression [ Time Frame: Once pre study and once at month 3 ] [ Designated as safety issue: No ]
  Colonic epithelial apoptosis and cell proliferation as assessed by immunohistochemical detection of cleaved caspase 3 and Ki-67, respectively once at pre study and once at month 3.
  
  
• Rectal prostaglandin levels as measured by ELISA [ Time Frame: Once at pre study and once at month 3 ] [ Designated as safety issue: No ]
  Rectal prostaglandin levels. These will be separate samples and, if in the unlikely event that there are not enough samples available for both, this will be considered lower priority than the 4-ELF-cellular parameter assessment once at pre study and once at month 3.
  
  
• Platelet cyclooxygenase (COX) activity as measured by a peroxidase-based COX enzyme activity assay [ Time Frame: Once at pre study and once at month 3 ] [ Designated as safety issue: No ]
  Platelet COX activity as measured by a peroxidase-based Cox enzyme activity assay once at pre study and once at month 3
  
  
• Correlation of spectral marker alterations with UGT1A6 genotype [ Time Frame: Once at pre study and once at month 3 ] [ Designated as safety issue: No ]
  UGT1A6 genotype. We will correlate the alterations with spectral markers with the genotype, hypothesizing that since UGT1A6 variant patients appear to have a better chemopreventive response from aspirin(1, 2), they should have a greater normalization of spectral markers. This will be considered lower priority over plasma COX activity if there is a limited amount of blood once at pre study and once at month 3.
  
  

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.