Oltipraz in the Prevention of Lung Cancer in People Who Smoke

June 7, 2012 updated by: Northwestern University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Raymond C. Bergan, MD, Robert H. Lurie Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2000

Primary Completion (Actual)

April 1, 2004

Study Completion (Actual)

April 1, 2004

Study Registration Dates

First Submitted

November 6, 2000

First Submitted That Met QC Criteria

May 29, 2003

First Posted (Estimate)

May 30, 2003

Study Record Updates

Last Update Posted (Estimate)

June 11, 2012

Last Update Submitted That Met QC Criteria

June 7, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI 00L1
  • NU-00L1
  • DUMC-000346-00-2
  • NCI-P00-0167

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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