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.

Condition	Treatment or Intervention	Phase
Small Cell Lung Cancer prevention of lung cancer Non-small cell lung cancer	Drug: chemoprevention of cancer  Procedure: cancer prevention intervention  Drug: oltipraz	Phase I

Further Study Details: 

OBJECTIVES: I. 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. II. Determine the tolerability and toxicity of this treatment regimen in these patients. III. 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. IV. 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. V. 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. VI. Compare the changes in oxidative state and phase II enzymes with changes in adduct levels in the lungs and blood of these patients. VII. 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. VIII. 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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--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

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States

Study chairs or principal investigators

Raymond C. Bergan,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000068190; NU-00L1; NCI-P00-0167; DUMC-000346-00-2
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  November 6, 2000
ClinicalTrials.gov Identifier:  NCT00006457
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08