RATIONALE: Chemoprevention therapy is the use of certain agents to try to prevent the development of cancer. The use of folic acid may be effective in preventing colorectal cancer. Eating a diet rich in folic acid may prevent the development of colorectal cancer.

PURPOSE: This randomized phase I trial is studying how well a folate-depleted diet works compared to a folate-supplemented diet in preventing colorectal cancer in patients who are at high risk for developing colorectal cancer.

Condition	Treatment or Intervention	Phase
Colon Cancer Rectal Cancer	Drug: folic acid  Procedure: biologically based therapies  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: complementary and alternative therapy  Procedure: dietary intervention  Procedure: dietary modification  Procedure: nutritional supplementation	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Analyze the effects of a folate-depleted vs a folate-supplemented diet on folate-related DNA endpoints (e.g., genomic and gene-specific DNA methylation and DNA strand breaks) in rectal epithelial cells in patients at high risk for colorectal neoplasia.
• Analyze the effects of these dietary interventions on folate-related DNA endpoints (e.g., genomic and gene-specific DNA methylation, DNA strand breaks, and uracil incorporation into DNA) in blood mononuclear cells in these patients.

Secondary

• Analyze the effects of these dietary interventions on the patterns of differential gene expression in rectal epithelial cells and blood mononuclear cells in these patients.

OUTLINE: This is a randomized, single-blind study.

• Run-in period: Patients are placed on an average folate-containing diet for 56 days.
• After completion of the run-in period, patients are randomized to 1 of 2 arms.
• Arm I (folate depleted diet): Patients are placed on a low-folate diet for 84 days. Patients receive oral folic acid supplementation once daily on days 57-84.
• Arm II (folate supplemented diet): Patients continue on an average folate-containing diet for an additional 56 days. Patients receive oral folic acid supplementation once daily on days 1-56. Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 20 patients (10 per arm) will be accrued for this study within 2.5 years.

Ages Eligible for Study:  40 Years   -   72 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

DISEASE CHARACTERISTICS:

• Healthy persons at increased risk for colorectal neoplasia due to 1 of the following reasons:
• Personal history of colorectal adenomatous polyps
• Family history of colorectal adenoma or adenocarcinoma
• No history of multiple family members with colorectal neoplasia that is suggestive of dominant hereditary neoplasia

PATIENT CHARACTERISTICS: Age

• 40 to 72

Performance status

• Ambulatory

Life expectancy

• At least 6 months

Hematopoietic

• No excessive bleeding or coagulation disorder

Hepatic

• ALT or AST ≤ 2 times upper limit of normal
• No unexplained elevated alkaline phosphatase

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• Homocysteine concentration ≤ 17um/L
• No sustained blood pressure > 150/95 mm Hg for 3 consecutive readings

Other

• Vitamin B_12 ≥ 250 pg/mL
• Folate level ≤ 20 mg/dL
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study participation
• No intestinal malabsorption or inflammatory bowel disease
• No prior malignancy except nonmelanoma skin cancer
• No calcium metabolism abnormalities or predisposing conditions, such as hyperparathyroidism
• No untreated hyperthyroidism
• No untreated insulin-requiring diabetes mellitus
• No daily alcohol intake > 2 ½ shot glasses of whiskey or three 8 ounce glasses of beer or wine
• No other serious illness that might limit life expectancy to < 6 months

PRIOR CONCURRENT THERAPY: Biologic therapy

• None

Chemotherapy

• None

Endocrine therapy

• No concurrent hormone replacement therapy, including oral, transplanted, or injected contraceptives
• Concurrent thyroid hormone replacement is allowed as long as the patient is euthyroid for 3 months

Radiotherapy

• None

Surgery

• No prior gastrointestinal surgery, including gastrectomy or small or large bowel resections
• Prior appendectomy or surgery of the esophagus allowed

Other

• More than 3 months since regular ingestion of ≥ 650 mg per day of aspirin (≥ 2 tablets of 325 mg regular strength OR > 1 tablet of 500 mg extra strength aspirin)
• More than 3 months since regular daily ingestion of nonsteroidal anti-inflammatory drugs
• At least 1 month since vitamin, mineral, or herbal supplementation
• No other concurrent vitamin, mineral, or herbal supplementation
• No concurrent anticoagulants
• No concurrent sterol-binding resins (i.e., cholestyramine)
• No other concurrent investigational drugs or medications that might alter rectal mucosal proliferation, folate metabolism, or renal/hepatic impairment
• No concurrent weight control medications
• No concurrent supplemental folate preparations containing > 400 mcg of folic acid per day
• No concurrent lipid-lowering medications
• The following concurrent statin drugs are allowed provided patient has been taking a stable dose for ≥ 1 month:
• Atorvastatin 10 or 20 mg/day
• Fluvastatin 20 or 40 mg/day
• Lovastatin 10 or 20 mg/day
• Pravastatin 10 or 20 mg/day
• Simivastatin 5 or 10 mg/day

Massachusetts
      Cancer Center at Tufts - New England Medical Center, Boston,  Massachusetts,  02111-1854,  United States; Recruiting
New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10461,  United States; Recruiting
      Rockefeller University Hospital, New York,  New York,  10021-6399,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-001,  United States; Recruiting
      Strang Cancer Prevention Center, New York,  New York,  10021-6399,  United States; Recruiting

Study chairs or principal investigators

Jim Marshall, PhD,  Principal Investigator,  Roswell Park Cancer Institute   

Study ID Numbers:  CDR0000393455; RUH-PHO-0514-0404; RPCI-EPR-20703; AECM-0401022E; NEMCH-6060; NCT00096330
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00096330
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08