Phase IIA Trial of Curcumin Among Patients With Prevalent Subclinical Neoplastic Lesions (Aberrant Crypt Foci)
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.
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
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
After completion of study therapy, patients are followed at 1 week.
PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Mean change from baseline in PGE2 within ACF pre and post 30 days of curcumin administration at a specified dose
The changes in ACF PGE2 will be calculated as absolute change from baseline in paired specimens of log-transformed values. The logarithmic transformation of PGE2 is applied only as required for variance stabilization. To estimate treatment effect, the median and 95% percent confidence interval for the median percent change will be calculated. Significance will be assessed by the distribution-free Sign test.
Baseline to 30 days
Chao Family Comprehensive Cancer Center
United States: Food and Drug Administration
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