Trial Information

PHASE II DOUBLE-BLIND CHEMOPREVENTION TRIAL OF HIGH DOSE FOLIC ACID VERSUS PLACEBO IN PATIENTS WITH RESECTED COLORECTAL POLYPS

OBJECTIVES: I. Determine whether high-dose folic acid decreases global DNA hypomethylation,
as well as other intermediary markers, in normal-appearing colonic epithelium of patients
with colonic adenomas. II. Determine whether a decrease in global DNA hypomethylation and
other intermediary markers can be induced safely and whether these effects persist after
folic acid is discontinued in these patients. III. Confirm pilot data that indicates
patients with adenomas have widespread DNA hypomethylation of the colorectal mucosa compared
to controls. IV. Evaluate the effect of folic acid on the clinical course and rate of
recurrence of adenomatous polyps in these patients. V. Study a control group of patients
with no history of neoplastic, hyperplastic, or inflammatory colorectal lesions.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to participating center and age (50-70 vs 30-49 and over 70).
Patients with adenomatous polyps at least 10 mm at colonoscopy are randomized to 1 of 2
treatment arms. Patients found to have no neoplastic, hyperplastic, or inflammatory polyps
at colonoscopy are assigned to a control (untreated) group and complete laboratory studies
and a baseline food frequency questionnaire only. Arm I: Patients receive folic acid daily.
Arm II: Patients receive placebo daily. Treatment continues in both arms for 1 year in the
absence of unacceptable toxicity or disease progression. Patients are followed at 1 year.

PROJECTED ACCRUAL: A total of 80 patients (30 per arm and 20 for the control group) will be
accrued for this study within 24 months.