Curcumin in Treating Patients With Familial Adenomatous Polyposis
|Familial Adenomatous Polyposis||Drug: Curcumin Other: Laboratory Biomarker Analysis Other: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)|
- Change in activation of NFKB pathway [ Time Frame: Baseline to up to 12 months ]
- Change in Akt phosphorylation levels [ Time Frame: Baseline to up to 12 months ]
- Change in apoptosis index levels [ Time Frame: Baseline to up to 12 months ]
- Change in Ki-67 anti-proliferative cell nuclear antibody index levels [ Time Frame: Baseline to up to 12 months ]
- Change in mucosa and adenoma histology assessed by light microscopy [ Time Frame: Baseline to up to 12 months ]
- Change in mucosal DNA methylation levels [ Time Frame: Baseline to up to 12 months ]
- Change in mucosal leukotriene levels [ Time Frame: Baseline to up to 12 months ]
- Change in mucosal prostaglandin levels [ Time Frame: Baseline to up to 12 months ]
- Change in ODC activity levels expressed as nmol of activity/mg of musosal tissue/hr [ Time Frame: Baseline to up to 12 months ]
- Change in polyamines levels expressed pg/mg protein [ Time Frame: Baseline to up to 12 months ]
- Change in vascular density [ Time Frame: Baseline to up to 12 months ]
- Incidence of grade >= 2 adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 12 months ]A safety review will be performed at the time of interim analysis.
- Mean polyp size in mm (mean size of the 5 largest polyps) [ Time Frame: Up to 16 months ]Continuous variables relating to colorectal proliferation and polyp size will be compared in the two treatment groups by parametric statistics.
- Medication compliance [ Time Frame: Up to 12 months ]
- Number of patients failing study [ Time Frame: Up to 16 months ]
- Side effects of curcumin treatment [ Time Frame: Up to 12 months ]
- Total number of polyps [ Time Frame: Up to 16 months ]The average number of polyps in the treatment groups will be compared by the t-test (or a distribution free analog if distribution assumptions are not met). Multivariate regression models will be used to adjust for strongly predictive factors that are not balanced in the treatment groups.
|Study Start Date:||October 2010|
|Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm I (curcumin)
Patients receive curcumin PO BID for 12 months.
Other Names:Other: Laboratory Biomarker Analysis
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID for 12 months.
Other: Laboratory Biomarker Analysis
Correlative studiesOther: Placebo
I. To determine in a randomized, double-blinded, placebo-controlled study the tolerability and effectiveness of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp number, and polyp size in familial adenomatous polyposis patients with intact colons, ileorectal anastomosis surgery, or ileo-anal pullthrough (reservoir) surgery.
II. To measure markers of cell proliferation including colorectal mucosal levels of ornithine decarboxylase (ODC), polyamines, mucosal deoxyribonucleic acid (DNA) methylation, proliferative index (Ki67 antiproliferative cell nuclear antibody), apoptosis index, vascular density, mucosal prostaglandin, leukotriene levels, and activation of the nuclear factor kappa B (NFKB), and v-akt murine thymoma viral oncogene homolog 1 (Akt) survival pathways.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive curcumin orally (PO) twice daily (BID) for 12 months.
ARM II: Patients receive placebo PO BID for 12 months.
After completion of study treatment, patients are followed up at 4 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00641147
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|University of Puerto Rico|
|San Juan, Puerto Rico, 00936|
|Principal Investigator:||Francis Giardiello||Johns Hopkins University/Sidney Kimmel Cancer Center|