Phase I Repeat-Dose Study of Resveratrol in Colorectal Cancer Patients: Tolerability, Target Tissue Levels and Pharmacodynamics
I. Determine the relationship between oral dose of resveratrol and the colon mucosal levels
of resveratrol and its metabolites in patients with resectable colorectal cancer.
II. Determine the relationship between colon mucosal levels of resveratrol and its
metabolites and plasma concentrations of resveratrol and its metabolites in these patients.
III. Determine cyclooxygenase-2 (COX-2) expression in colorectal cancer tissue before and
after treatment in these patients.
IV. Determine M_1G concentration in colonic cancer tissue and in circulating white blood
cells (WBC) before and after treatment.
V. Correlate M_1G concentration in colorectal cancer tissue with M_1G concentration in
VI. Assess the Ki67 labeling index in normal and malignant tissues in at least 10 fields per
VII. Correlate COX-2 expression in colorectal cancer tissue with COX-2 expression in
VIII. Assess the toxicity profile of this drug.
OUTLINE: This is a two-stage nonrandomized, open-label study. Patients are assigned to 1 of
2 dose levels in stage 2.
STAGE I: Patients undergo an colorectal endoscopy. Patients whose biopsies confirm
colorectal adenocarcinoma histology and require surgical resection continue on study stage
STAGE II: Patients receive oral resveratrol on days 1-8. Patients undergo colorectomy on day
9. A tumor biopsy is performed during endoscopy and colorectomy for research purposes.
Two biomarkers of the potential activity of resveratrol are measured in nonmalignant and
malignant colorectal tissue biopsy samples: levels of M_1G adducts by immunoslot blot
analysis and levels of cyclooxygenase-2 protein/Ki67 by immunohistochemistry. Blood samples
are collected at baseline and during colorectomy for analysis of resveratrol and its
metabolites and other pharmacokinetic studies.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pharmacodynamics of resveratrol
Up to 8 days
University of Michigan University Hospital
United States: Food and Drug Administration
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