Clinical trial NCT00365209
Conditions: Healthy, no Evidence of Disease Tobacco Use Disorder
Sponsor: National Cancer Institute (NCI)
Start date: 2006-10-01; Completion date: 2011-01-01
Enrollment: 44 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. Curcumin is a compound found in plants that may prevent colon cancer from forming. This phase II trial is studying how well curcumin works in preventing colon cancer in smokers with aberrant crypt foci.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine mean percentage change from baseline in prostaglandin E2 (PGE2) within ACF pre and post 30 days of curcumin administration at a specified dose.

SECONDARY OBJECTIVS:

I. To determine mean percentage change from baseline in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF pre and post 30 days of curcumin administration at a specified dose.

II. To determine mean percentage change from baseline in PGE2 and 5-HETE within comparison normal mucosa pre and post 30 days of curcumin administration at a specified dose.

III. To quantify corresponding enzyme changes in the cyclooxygenases (COX-1, COX-2,) and lipoxygenase (5-LOX) protein abundance. Semi-quantitative changes in these proteins will be measured by western blotting and correlated with changes in prostaglandins and leukotrienes respectively.

IV. Document changes in total ACF number. V. Determine proliferation by Ki-67 IHC in rectal mucosa pre and post therapy and correlate with changes in ACF number and size.

VI. Determine curcumin concentration in rectal mucosa after 30 days therapy and correlate with PGE2 and 5-HETE changes described above.

VII. Measure glutathione peroxidase (GPx) activity within the colon pre and post therapy as an indirect marker of reduced oxidative stress within the colonic epithelium.

VIII. Ensure safety of all participants during course of study investigation. IX. Determine the curcumin concentration in plasma before and after treatment.

OUTLINE: This is a multicenter, nonrandomized, uncontrolled study.

Patients receive 1 of 2 doses of oral curcumin once daily. Treatment continues for 30 days in the absence of unacceptable toxicity or disease progression.

Blood and tissue biopsies are obtained by sigmoidoscopy or colonoscopy at baseline and at day 30 for correlative biomarker studies. The change in prostaglandin E\_2 (PGE\_2) is assessed by enzyme immunoassay, 5-hydroxy-eicosatetraenoic acid (5-HETE) by high-performance liquid chromatography, cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) by western blotting, Ki-67 by immunohistochemistry, and glutathione peroxidase (GPx) by spectrophotometric assay.

After completion of study therapy, patients are followed at 1 week.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.

Arms: arm 1: Patients receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. arm 2: Patients receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.
Interventions: intervention 1: laboratory biomarker analysis intervention 2: pharmacological study intervention 3: curcumin
Intervention descriptions: intervention 1: Correlative studies intervention 2: Correlative studies intervention 3: Given orally

Protocol documents: