Clinical trial NCT00433576: Resveratrol in Treating Patients With Colorectal Cancer That Can Be Removed By Surgery
Official title: Phase I Repeat-Dose Study of Resveratrol in Colorectal Cancer Patients: Tolerability, Target Tissue Levels and Pharmacodynamics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-02-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pharmacodynamics of resveratrol
timeFrame: Up to 8 days
measure: Concentrations of biomarkers
timeFrame: Up to day 9
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Dean Brenner
role: PRINCIPAL_INVESTIGATOR
References: