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Phase I Clinical Study of Folate


Phase 1
40 Years
72 Years
Not Enrolling
Both
Colorectal Cancer

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Trial Information

Phase I Clinical Study of Folate


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.

- Randomization: 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.

Inclusion 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

- Simvastatin 5 or 10 mg/day

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

•Analyze the effects of a folate-depleted vs a folate-supplemented diet on folate-related DNA endpoints

Outcome Time Frame:

pre and post treatment

Safety Issue:

No

Principal Investigator

James Marshall, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000393455

NCT ID:

NCT00096330

Start Date:

September 2004

Completion Date:

March 2008

Related Keywords:

  • Colorectal Cancer
  • colon cancer
  • rectal cancer
  • Colorectal Neoplasms

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263