Curcumin in Preventing Colon Cancer in Smokers With Aberrant Crypt Foci

Official Title: “Phase II A Trial of Curcumin Among Patients With Prevalent Subclinical Neoplastic Lesions (Aberrant Crypt Foci)”

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.

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.

Intervention(s) in this Clinical Trial

• Dietary Supplement: curcumin
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Curcumin

Primary Measures

• Mean percentage change in prostaglandin E2 (PGE2) within aberrant cryptic foci (ACF) from baseline to 30 days after treatment with curcumin
  • Time Frame: 30 days post-treatment
    Safety Issue?: No

Secondary Measures

• Mean percentage change in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF from baseline to 30 days after treatment with curcumin
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Mean percentage change in PGE2 and 5-HETE in normal mucosa from baseline to 30 days after treatment with curcumin
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Changes in cyclooxygenases (COX-1 and COX-2) and lipoxygenase (5-LOX) protein abundance
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Changes in total ACF number
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Proliferation of Ki-67 in rectal mucosa by immunohistochemistry before and after treatment with curcumin
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Correlation of proliferation of Ki-67 in rectal mucosa with changes in ACF number and size
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Curcumin concentration in rectal mucosa after 30 days of treatment with curcumin
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Correlation of curcumin concentration in rectal mucosa with PGE2 and 5-HETE changes
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Glutathione peroxidase (GP-x) activity within the colon before and after treatment with curcumin
  • Time Frame: 30 days post-treatment
    Safety Issue?: No
• Ensure safety of all participants during course of study investigation
  • Time Frame: 37 days post-treatment
    Safety Issue?: Yes
• Determine curcumin concentration in plasma before and after treatment
  • Time Frame: 30 days post-treatment
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of California, Irvine Other

Overall Clinical Trial Officials and Contacts

Frank L. Meyskens, MD, FACP Principal Investigator Chao Family Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00365209

Study ID Number: CDR0000483003

ClinicalTrials.gov Identifier: NCT00365209

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database

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