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

NCT ID: NCT00433576

Last Updated: 2014-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2009-03-31

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

resveratrol

Intervention Type: DRUG

Given orally

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

resveratrol

Given orally

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

pharmacological studies

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dean Brenner

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

NCI-2009-00864

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000528296

Identifier Type: -

Identifier Source: secondary_id

LRI-6930

Identifier Type: -

Identifier Source: secondary_id

N01-CN-25025

Identifier Type: -

Identifier Source: secondary_id

CCUM-TASK2B

Identifier Type: OTHER

Identifier Source: secondary_id

N01-CN-25025-4

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA046592

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00864

Identifier Type: -

Identifier Source: org_study_id