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Phase I Repeat-Dose Study of Resveratrol in Colorectal Cancer Patients: Tolerability, Target Tissue Levels and Pharmacodynamics

Phase 1
18 Years
Not Enrolling
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Stage I Colon Cancer, Stage I Rectal Cancer, Stage II Colon Cancer, Stage II Rectal Cancer, Stage III Colon Cancer, Stage III Rectal Cancer

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Trial Information

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
circulating WBC.

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
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

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.

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pharmacodynamics of resveratrol

Outcome Time Frame:

Up to 8 days

Safety Issue:


Principal Investigator

Dean Brenner

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan University Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

December 2006

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum
  • Stage I Colon Cancer
  • Stage I Rectal Cancer
  • Stage II Colon Cancer
  • Stage II Rectal Cancer
  • Stage III Colon Cancer
  • Stage III Rectal Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms



University of Michigan University Hospital Ann Arbor, Michigan  48109