Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Stage I Colon Cancer, Stage II Colon Cancer, Stage III Colon Cancer, Stage III Rectal Cancer, Stage II Rectal Cancer, Stage I Rectal Cancer
Conditions
Brief summary
This phase I trial is studying the side effects and best dose of resveratrol in treating patients with colorectal cancer that can be removed by surgery. Resveratrol may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
OBJECTIVES: 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 circulating WBC. VI. Assess the Ki67 labeling index in normal and malignant tissues in at least 10 fields per section. VII. Correlate COX-2 expression in colorectal cancer tissue with COX-2 expression in circulating WBCs. 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 2. 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.
Interventions
DRUGresveratrol
Given orally
OTHERpharmacological study
Correlative studies
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage 1: * Radiological or clinical evidence of a colorectal malignancy * Requires colorectal endoscopy for diagnosis * Stage 2: * Histologically confirmed adenocarcinoma of the colon or rectum by colorectal endoscopy in stage 1 study * Resectable disease * Planning to undergo colorectomy * WHO performance status 0-2 * ALT ≤ 2.5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 times ULN * Creatinine ≤ 1.5 mg/dL * Hemoglobin ≥ 10 g/dL (transfusion allowed for anemia due to bleeding from the tumor) * Suitable for general anesthesia * No active peptic ulcer disease * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No excessive alcohol intake (more than UK recommended limit: 28 or 21 units per week for men or women, respectively) * No other cancer that is currently under treatment, clinically detectable, or has been treated within the past 5 years (other than basal cell or squamous cell carcinomas) * At least 6 months since prior and no concurrent participation in other invasive or drug studies * No radiotherapy or chemotherapy within 4 weeks of endoscopic tissue sampling * At least 24 hours since prior and no concurrent nonessential medications or nonsteroidal anti-inflammatory drugs * No concurrent resveratrol-containing food and drink (e.g., wine, grapes, peanuts, mulberries, cranberries, blueberries, huckleberries) * No concurrent vitamin supplements * No concurrent chronic medications, including over-the-counter medications, that may interfere with the pharmacokinetics or pharmacodynamics measured * No concurrent medication that could interfere with biomarker assay * No concurrent anticoagulants including, warfarin and low molecular weight heparin * No concurrent steroids
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacodynamics of resveratrol | Up to 8 days |
| Concentrations of biomarkers | Up to day 9 |
Countries
United States
Outcome results
None listed