Oltipraz in the Prevention of Lung Cancer in People Who Smoke
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer.
PURPOSE: Randomized phase I trial to study the effectiveness of oltipraz in preventing lung cancer in people who smoke.
|Study Design:||Allocation: Randomized
Primary Purpose: Prevention
|Official Title:||Clinical Phase I Multiple-Dose Safety Research Study of Oltipraz in Smokers|
|Study Start Date:||August 2000|
|Study Completion Date:||April 2004|
|Primary Completion Date:||April 2004 (Final data collection date for primary outcome measure)|
- 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 smokers.
- 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 patients.
- 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 these patients.
- 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.
|United States, Illinois|
|Robert H. Lurie Comprehensive Cancer Center, Northwestern University|
|Chicago, Illinois, United States, 60611-3013|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Study Chair:||Raymond C. Bergan, MD||Robert H. Lurie Cancer Center|