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

Adenocarcinoma of the Rectum Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00433576
• Other study ID #: NCI-2009-00864
• Secondary ID: NCI-2009-00864CD
• Status: Completed
• Phase: Phase 1
• First received: February 8, 2007
• Last updated: September 12, 2014
• Start date: December 2006
• Est. completion date: March 2009

Study information

• Verified date: October 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2009
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• resveratrol
Given orally

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacodynamics of resveratrol		Up to 8 days	No
Primary	Concentrations of biomarkers		Up to day 9	No