Resveratrol in Treating Patients With Colorectal Cancer That Can Be Removed By Surgery

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

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.

Study Overview

• Status: Completed
• Conditions: 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 of the Colon
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: resveratrol

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (resveratrol, colorectomy); 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.

Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: resveratrol; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics of resveratrol	Up to 8 days
Concentrations of biomarkers	Up to day 9

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Dean Brenner, University of Michigan

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: February 8, 2007
• First Submitted That Met QC Criteria: February 8, 2007
• First Posted (Estimate): February 12, 2007

Study Record Updates

• Last Update Posted (Estimate): September 15, 2014
• Last Update Submitted That Met QC Criteria: September 12, 2014
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: NCI-2009-00864 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA046592 (U.S. NIH Grant/Contract); CDR0000528296; LRI-6930; N01-CN-25025; CCUM-TASK2B (Other Identifier: University of Michigan); N01-CN-25025-4 (Other Identifier: DCP)