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

Phase 1
18 Years
Not Enrolling
Lung Cancer

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Trial Information

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


- 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

- 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

- 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


- 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

- 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



- 18 and over

Performance status:

- ECOG 0

Life expectancy:

- Not specified


- CBC normal

- Hemostasis normal


- PT and PTT normal


- Blood chemistries normal

- Nonfasting glucose no greater than 200 mg/dL

- No active renal disease

- No urinary tract infection by urinalysis (trace protein allowed)


- EKG normal

- No coronary artery disease requiring continuous medication


- 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


- 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

- 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


Biologic therapy:

- Not specified


- At least 3 months since prior potential chemoprevention agent (e.g., oltipraz,
retinoids, or acetylcysteine)

Endocrine therapy:

- Not specified


- Not specified


- See Disease Characteristics

Type of Study:


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


United States: Federal Government

Study ID:

NCI 00L1



Start Date:

August 2000

Completion Date:

April 2004

Related Keywords:

  • Lung Cancer
  • non-small cell lung cancer
  • small cell lung cancer
  • Lung Neoplasms



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