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

• ClinicalTrials.gov Identifier: NCT00433576
• Recruitment Status: Completed
• First Posted: February 12, 2007
• Last Update Posted: September 15, 2014
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Repeat-Dose Study of Resveratrol in Colorectal Cancer Patients: Tolerability, Target Tissue Levels and Pharmacodynamics
• Study Start Date: December 2006
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: March 2009

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures :

1. Pharmacodynamics of resveratrol [ Time Frame: Up to 8 days ]
2. Concentrations of biomarkers [ Time Frame: Up to day 9 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Dean Brenner; University of Michigan

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00433576
• Other Study ID Numbers: NCI-2009-00864; NCI-2009-00864 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000528296; LRI-6930; N01-CN-25025; CCUM-TASK2B ( Other Identifier: University of Michigan ); N01-CN-25025-4 ( Other Identifier: DCP ); P30CA046592 ( U.S. NIH Grant/Contract )
• First Posted: February 12, 2007
• Last Update Posted: September 15, 2014
• Last Verified: October 2011

Additional relevant MeSH terms:

Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Resveratrol; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Enzyme Inhibitors; Platelet Aggregation Inhibitors