RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of folic acid may be an effective way to prevent colorectal cancer in patients with polyps that have been surgically removed. PURPOSE: Randomized phase II trial to study the effectiveness of high-dose folic acid in preventing colorectal cancer in patients who have had polyps surgically removed within 18 months of the trial.

Condition	Treatment or Intervention	Phase
Rectal Cancer prevention of colorectal cancer Colon Cancer	Drug: folic acid	Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  21 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Colonic adenoma(s) of at least 10 mm completely resected within 18 months prior to randomization or suspected adenomatous polyp(s)
• Colonoscopy with submission of at least 7 rectosigmoid biopsies required at entry; No benign hyperplastic polyps or polyps less than 10 mm to be eligible for treatment; No polyposis coli (i.e., more than 100 polyps in colon)
• No history of invasive colorectal cancer

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No concurrent methotrexate
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: See Disease Characteristics; No prior small bowel resection
• Other: No concurrent anticonvulsants; No concurrent drugs that markedly interfere with folate absorption or metabolism (e.g., sulfasalazine and phenytoin); No concurrent vitamins during and for 2 years after beginning of study

--Patient Characteristics--

• Age: 21 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Platelet count greater than 100,000/mm3; Hemoglobin greater than 10 g/dL; No untreated pernicious anemia
• Hepatic: Bilirubin less than 2 mg/dL; ALT less than 2 times normal; Alkaline phosphatase less than 2 times normal; PT normal
• Renal: Not specified
• Gastrointestinal: No intestinal malabsorption; No inflammatory bowel disease
• Other: No seizure within the past year; No poor medical risk; No other malignancy within past 5 years except basal cell cancer, superficial skin cancer, or carcinoma in situ of the cervix; No vitamin B12 deficiency (less than 200 pg/mL); Not pregnant or nursing; Fertile patients must use effective barrier contraception

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
      New England Medical Center Hospital, Boston,  Massachusetts,  02111,  United States
      USDA Human Nutrition Research Center, Boston,  Massachusetts,  02111,  United States
New York
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Veterans Affairs Medical Center - New York, New York,  New York,  10010,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States

Study chairs or principal investigators

Joel Mason,  Study Chair,  Eastern Cooperative Oncology Group   

Study ID Numbers:  CDR0000064180; E-8292; NCI-P95-0066
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002650
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08