Clinical Phase I Multiple-Dose Safety Research Study of Oltipraz in Smokers
18 Years
N/A
Both
Lung Cancer
Trial Information
Clinical Phase I Multiple-Dose Safety Research Study of Oltipraz in Smokers
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention
Principal Investigator
Raymond C. Bergan, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Robert H. Lurie Cancer Center
Authority:
United States: Federal Government
Study ID:
NCI 00L1
NCT ID:
NCT00006457
Start Date:
August 2000
Completion Date:
April 2004
Related Keywords:
- Lung Cancer
- non-small cell lung cancer
- small cell lung cancer
- Lung Neoplasms
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Robert H. Lurie Comprehensive Cancer Center, Northwestern University | Chicago, Illinois 60611 |
