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Phase II Chemoprevention Study of Curcumin in Current Smokers With Aberrant Crypt Foci
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
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Status
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Age
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Sponsor
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Protocol IDs
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Phase II
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Biomarker/Laboratory analysis, Prevention
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Closed
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40 and over
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NCI
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UCIRVINE-UCI04-2-01 UCIRVINE-2005-4586, UIC-2005-0617, CCUM-HUM00000731, UCI04-2-01, NCT00365209
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Special Category:
NCI Web site featured trial Objectives Primary - 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 - 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 PGE2 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 and size, as well as the individual change in a previously marked ACF in patients treated with curcumin.
- 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 PGE2 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.
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 48A total of 48 patients will be accrued for this study. Outcomes Primary Outcome(s)Mean percentage change in prostaglandin E2 (PGE2) within aberrant cryptic foci (ACF) from baseline to 30 days after treatment with curcumin
Secondary Outcome(s)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 | | | |
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 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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