Oltipraz in the Prevention of Lung Cancer in People Who Smoke

NCT ID: NCT00006457

Last Updated: 2012-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-08-31
• Study Completion Date: 2004-04-30

Brief Summary

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

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Interventions

oltipraz

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raymond C. Bergan, MD

Role: STUDY_CHAIR

Robert H. Lurie Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

NU-00L1

Identifier Type: -

Identifier Source: secondary_id

DUMC-000346-00-2

Identifier Type: -

Identifier Source: secondary_id

NCI-P00-0167

Identifier Type: -

Identifier Source: secondary_id

NCI 00L1

Identifier Type: -

Identifier Source: org_study_id