Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: 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.

PURPOSE: This phase II trial is studying how well curcumin works in preventing colon cancer in smokers with aberrant crypt foci.

Further Study Information

OBJECTIVES:

Primary

• Determine mean percentage change in prostaglandin E_2 (PGE_2) within aberrant crypt foci (ACF) from baseline to 30 days after treatment with curcumin in current smokers.

Secondary

• Determine the mean percentage change in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF from baseline to 30 days after treatment with curcumin in these patients.

• Determine the mean percentage change in PGE_2 and 5-HETE within normal mucosa from baseline to 30 days after treatment with curcumin in these patients.

• Quantify corresponding enzyme changes in the cyclooxygenases (COX-1 and COX-2) and lipoxygenase (5-LOX) protein abundance in patients treated with curcumin.

• Document changes in total ACF number.

• Determine proliferation by Ki-67 immunohistochemistry (IHC) in rectal mucosa before and after treatment with curcumin and correlate changes in ACF number and size in these patients.

• Determine curcumin concentration in rectal mucosa after 30 days of treatment with curcumin and correlate with PGE_2 and 5-HETE changes described above in these patients.

• Measure glutathione peroxidase (GPx) activity within the colon before and after treatment with curcumin as an indirect marker of reduced oxidative stress within the colonic epithelium in these patients.

• Ensure the safety of all patients during course of study investigation.

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.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Current smokers who have smoked > 3 total pack years

• At least 8 aberrant crypt foci by magnification chromoendoscopy

• No newly diagnosed colorectal cancer or advanced adenoma within the past year

• No hereditary colon cancer syndromes (familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer)

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100%

• No severe organ dysfunction that might increase bleeding risk

• WBC > 3,000/mm³

• Hemoglobin > 10.0 g/dL

• Platelet count >100,000/mm³

• Bilirubin < 1.5 mg/dL

• Transaminases < 1.5 times upper limit of normal

• Creatinine < 2.0 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No history of any of the following:

• Chronic inflammatory bowel disease

• Peptic ulcer disease endoscopically confirmed within the past 5 years

• Unspecified bleeding or coagulation disorder

• Contact dermatitis from turmeric

• No uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

• No prior pelvic irradiation

• More than 14 days since prior limited (< 10 days/month) and no concurrent nonsteroidal anti-inflammatory drugs or acetylsalicylic acid

• No concurrent glucocorticoids or omega 3-fatty acid supplements

• No other concurrent investigational agents

Trial Contact Information

Trial Lead Organizations/Sponsors

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Frank L. Meyskens

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00365209
Information obtained from ClinicalTrials.gov on December 14, 2011

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