Oltipraz in the Prevention of Lung Cancer in People Who Smoke - Full Text View

Sponsor:	Robert H. Lurie Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00006457

Purpose

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	Intervention	Phase
Lung Cancer	Drug: oltipraz	Phase I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Active Control
Official Title:	Clinical Phase I Multiple-Dose Safety Research Study of Oltipraz in Smokers

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Smoking

Drug Information available for: Oltipraz

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	August 2000
Primary Completion Date:	November 2003 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006457

Locations

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

Sponsors and Collaborators

Robert H. Lurie Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Raymond C. Bergan, MD

Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000068190, NU-00L1, DUMC-000346-00-2, NCI-P00-0167
Study First Received:	November 6, 2000
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00006457 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

non-small cell lung cancer
small cell lung cancer

Additional relevant MeSH terms:

Thoracic Neoplasms
Anticarcinogenic Agents
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Reverse Transcriptase Inhibitors
Antiparasitic Agents
Neoplasms by Site
Respiratory Tract Diseases
Anti-Retroviral Agents
Lung Neoplasms
Therapeutic Uses

Oltipraz
Nucleic Acid Synthesis Inhibitors
Respiratory Tract Neoplasms
Antiplatyhelmintic Agents
Anthelmintics
Enzyme Inhibitors
Schistosomicides
Antiviral Agents
Protective Agents
Pharmacologic Actions
Neoplasms
Lung Diseases

ClinicalTrials.gov processed this record on November 05, 2009