Clinical trial NCT00002650: High-Dose Folic Acid in Preventing Colorectal Cancer in Patients Who Have Had Polyps Surgically Removed
Official title: PHASE II DOUBLE-BLIND CHEMOPREVENTION TRIAL OF HIGH DOSE FOLIC ACID VERSUS PLACEBO IN PATIENTS WITH RESECTED COLORECTAL POLYPS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: colon cancer
rectal cancer
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-03-11
Enrollment: 80
Sex: ALL
Minimum age (years): 21
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility 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

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

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Boston
country: United States
facility: New England Medical Center Hospital
state: Massachusetts
city: Boston
country: United States
facility: USDA Human Nutrition Research Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: New York
country: United States
facility: Veterans Affairs Medical Center - New York
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
Study officials:
affiliation: Tufts Medical Center Cancer Center
name: Joel Mason, MD
role: STUDY_CHAIR
References: