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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00433576
First received: February 8, 2007
Last updated: May 1, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: resveratrol
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Repeat-Dose Study of Resveratrol in Colorectal Cancer Patients: Tolerability, Target Tissue Levels and Pharmacodynamics

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pharmacodynamics of resveratrol [ Time Frame: Up to 8 days ] [ Designated as safety issue: No ]
  • Concentrations of biomarkers [ Time Frame: Up to day 9 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: December 2006
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433576

Locations
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Investigators
Principal Investigator: Dean Brenner University of Michigan University Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00433576     History of Changes
Other Study ID Numbers: NCI-2009-00864, CCUM-TASK2B, LRI-6930, CDR0000528296, N01-CN-25025-4
Study First Received: February 8, 2007
Last Updated: May 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Resveratrol
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 21, 2014