Oltipraz in the Prevention of Lung Cancer in People Who Smoke

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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.

Official Title
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Clinical Phase I Multiple-Dose Safety Research Study of Oltipraz in Smokers

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: oltipraz


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Current cigarette smokers At least 20 cigarettes a day No variation of more than 10 in the number of cigarettes smoked per day within the past 3 months At least 10 years of smoking any amount Failed to stop smoking after at least one attempt to quit within the last 3 years Prior stage I non-small cell lung cancer allowed if surgically resected with at least a lobectomy No concurrent evidence of lung cancer Willing to undergo 2 bronchoscopies PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0 Life expectancy: Not specified Hematopoietic: CBC normal Hemostasis normal Hepatic: PT and PTT normal Renal: Blood chemistries normal Nonfasting glucose no greater than 200 mg/dL No active renal disease No urinary tract infection by urinalysis (trace protein allowed) Cardiovascular: EKG normal No coronary artery disease requiring continuous medication Pulmonary: Chest radiograph normal (postsurgical changes allowed) No acute or significant chronic abnormality FEV1 greater than 1.8 L or 75% predicted No chronic obstructive pulmonary disease requiring continuous medication Other: No known hypersensitivity or prior adverse reaction to oltipraz No inmates or prisoners No medical or psychological condition that would preclude study (e.g., acute psychosis) No prior malignancy except nonmelanomatous skin cancer, cervical dysplasia, or curatively treated stage I or II cancer of the head and neck Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 3 months since prior potential chemoprevention agent (e.g., oltipraz, retinoids, or acetylcysteine) Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: oltipraz|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, small cell lung cancer