Clinical Phase I Multiple-Dose Safety Research Study of Oltipraz in Smokers
- Determine the effect of oltipraz on the level of BP-7,8-diol-9,10-epoxide (BPDE) DNA
adducts in the lung lining cells (macrophages and bronchial epithelial cells) of
- Determine the tolerability and toxicity of this treatment regimen in these patients.
- Determine the effect of this treatment regimen on the level of macromolecule adducts in
the blood (e.g., BPDE DNA, BPDE hemoglobin, and 8-hydroxy-deoxyguanine), oral lining
cells (BPDE DNA), bladder lining cells (4-aminobiphenyl DNA), and lung macrophages
(8-hydroxy-deoxyguanine) in these patients.
- Determine the effect of this treatment regimen on the change (decrease) in activation
of NNK as measured by change (increase) in urinary NNAL plus NNAL glucuronide in these
- Determine the effect of this treatment regimen on the oxidative state,
glutathione-S-transferase activity, and superoxide dismutase 3 and phase II enzymes in
the lungs and blood of these patients.
- Compare the changes in oxidative state and phase II enzymes with changes in adduct
levels in the lungs and blood of these patients.
- Determine the correlation between oltipraz-induced changes in phase II enzymes and
adduct formation with genotypic variation in glutathione-S-transferase isozymes in
- Compare the response to this treatment regimen in terms of oxidative state, phase II
enzymes, and adduct formation in the lungs vs the blood in these patients.
OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified
according to participating center. Patients are randomized to one of three treatment arms.
- Arm I: Patients receive an oral placebo weekly.
- Arm II: Patients receive low-dose oral oltipraz weekly.
- Arm III: Patients receive high-dose oral oltipraz weekly. Treatment continues for 12
weeks in the absence of unacceptable toxicity.
Patients are followed at 4 weeks.
PROJECTED ACCRUAL: A total of 66 patients (22 per treatment arm) will be accrued for this
study within 21 months.
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Raymond C. Bergan, MD
Robert H. Lurie Cancer Center
United States: Federal Government
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|Robert H. Lurie Comprehensive Cancer Center, Northwestern University||Chicago, Illinois 60611|