Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Curcumin in Preventing Colon Cancer in Smokers With Aberrant Crypt Foci

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Prevention Closed 40 and over NCI UCIRVINE-UCI04-2-01 UCIRVINE-2005-4586, UIC-2005-0617, CCUM-HUM00000731, UCI04-2-01, NCT00365209

Special Category: NCI Web site featured trial

Objectives

Primary

1. Determine mean percentage change in prostaglandin E₂ (PGE₂) within aberrant crypt foci (ACF) from baseline to 30 days after treatment with curcumin in current smokers.

Secondary

1. 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.
2. Determine the mean percentage change in PGE₂ and 5-HETE within normal mucosa from baseline to 30 days after treatment with curcumin in these patients.
3. Quantify corresponding enzyme changes in the cyclooxygenases (COX-1 and COX-2) and lipoxygenase (5-LOX) protein abundance in patients treated with curcumin.
4. Document changes in total ACF number and size, as well as the individual change in a previously marked ACF in patients treated with curcumin.
5. 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.
6. Determine curcumin concentration in rectal mucosa after 30 days of treatment with curcumin and correlate with PGE₂ and 5-HETE changes described above in these patients.
7. 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.
8. Ensure the safety of all patients during course of study investigation.

Entry 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)

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

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

Expected Enrollment

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

Outcomes

Mean percentage change in prostaglandin E2 (PGE2) within aberrant cryptic foci (ACF) from baseline to 30 days after treatment with curcumin

Mean percentage change in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF from baseline to 30 days after treatment with curcumin
Mean percentage change in PGE2 and 5-HETE in normal mucosa from baseline to 30 days after treatment with curcumin
Changes in cyclooxygenases (COX-1 and COX-2) and lipoxygenase (5-LOX) protein abundance
Changes in total ACF number and size
Individual change in a previously marked ACF
Proliferation of Ki-67 in rectal mucosa by immunohistochemistry before and after treatment with curcumin
Correlation of proliferation of Ki-67 in rectal mucosa with changes in ACF number and size
Curcumin concentration in rectal mucosa after 30 days of treatment with curcumin
Correlation of curcumin concentration in rectal mucosa with PGE2 and 5-HETE changes
Glutathione peroxidase (GP-x) activity within the colon before and after treatment with curcumin

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 E₂ (PGE₂) 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.

Trial Contact Information

Trial Lead Organizations

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

Frank Meyskens, MD, FACP, Principal investigator		Ph: 714-456-6310 Email: flmeyske@uci.edu

Related Information

Featured trial article

Registry Information
Official Title		Phase II A Trial of Curcumin Among Patients with Prevalent Subclinical Neoplastic Lesions (Aberrant Crypt Foci)
Trial Start Date		2006-09-29
Registered in ClinicalTrials.gov		NCT00365209
Date Submitted to PDQ		2006-04-28
Information Last Verified		2008-04-15
NCI Grant/Contract Number		CN35160, CA62203