Oltipraz in the Prevention of Lung Cancer in People Who Smoke

Original Study ID : CDR0000068190

Secondary ID : Array

NCT ID : NCT00006457

Brief Title : Oltipraz in the Prevention of Lung Cancer in People Who Smoke

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

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.

Source : National Cancer Institute (NCI)

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.

Overall Status : Active, not recruiting

Start Date : August 2000

Official Title : Phase 1

Phase : Interventional

Study Design : Prevention, Randomized, Double-Blind, Active Control

Verification Date : July 2002

First Received Date : November 6, 2000

Trial Eligibility

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

Gender : Both

Minimum Age : 18 Years

Maximum Age : N/A

Healthy Volunteers : No

Facilities

Facility Name : Robert H. Lurie Comprehensive Cancer Center, Northwestern University

City : Chicago

State : Illinois

Zip Code : 60611-3013

Country : United States

Facility Name : Duke Comprehensive Cancer Center

City : Durham

State : North Carolina

Zip Code : 27710

Country : United States

Interventions

Type : Drug

Name : oltipraz

Clinical Trial Name - Oltipraz in the Prevention of Lung Cancer in People Who Smoke