High-Dose Folic Acid in Preventing Colorectal Cancer in Patients Who Have Had Polyps Surgically Removed

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Dietary supplement: folic acid

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Joel Mason, MD, Tufts Medical Center Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 1995
• Primary Completion (Actual): October 17, 2004
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: March 10, 2004
• First Posted (Estimated): March 11, 2004

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: rectal cancer; colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid
• Other Study ID Numbers: CDR0000064180; E-8292; NCI-P95-0066