Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers

NCT01021215 | Completed Phase 1 Results

• 3 other identifiers: NCI-2013-007302009-0804N01CN35159
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical research study is to learn how zileuton alone or the combination of zileuton and celecoxib may affect certain chemicals in the body that may be linked with a risk for smoking-related lung disease. These effects will be measured by a urine test

Conditions

Tobacco Use Disorder

Keywords

Cancer Prevention; Smoking-related lung disease; Smoking; Celecoxib; Celebrex; Zileuton; Zyflo CR; Prevention

Outcome Measures

Primary Outcomes (2)

• Median Urinary PGE-M Levels (Pre and Post Treatment)

  Pre and Post treatment differences in urinary PGE-M levels measured in each treatment arm. PGE-M levels reported as median with full range (ng/mg creatinine) for Pre treatment versus Post treatment PGE-M levels among study participants compliant to treatment with evaluable urine samples at both time points (baseline and Day 6 +/- 1 day).

  Baseline and Day 6

• Median Urinary LTE4 Levels (Pre and Post Treatment)

  Pre and Post treatment differences in urinary LTE4 levels measured in each treatment arm compared using paired t-test should the data conform to the normality assumption or one-sample Wilcoxon rank-sum test. LTE4 levels reported as median with full range (pg/mg creatinine) for Pre treatment versus Post treatment LTE4 levels among study participants compliant to treatment with evaluable urine samples at both time points (baseline and Day 6 +/- 1 day).

  Baseline and day 6

Secondary Outcomes (1)

• Proportion of Cases With a Post-treatment Increase in Urinary PGE-M Levels

  Baseline to Day 6

Study Arms (2)

Arm I: Zileuton

EXPERIMENTAL

Zileuton 1200 mg twice orally twice a day on days 1-6.

Drug: Zileuton; Other: laboratory biomarker analysis

Arm II: Zileuton and Celecoxib

EXPERIMENTAL

Combined Zileuton 1200 mg twice daily plus Celecoxib 200 mg twice daily on days 1-6.

Drug: Zileuton; Drug: Celecoxib; Other: laboratory biomarker analysis

Interventions

Zileuton DRUG

1200 mg twice daily given orally (PO) for 6 days

Also known as: Zyflo CR

Arm I: Zileuton; Arm II: Zileuton and Celecoxib

Celecoxib DRUG

200 mg twice daily given orally for 6 days

Also known as: Celebrex

Arm II: Zileuton and Celecoxib

laboratory biomarker analysis OTHER

Correlative studies

Arm I: Zileuton; Arm II: Zileuton and Celecoxib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female current tobacco smokers with more or equal to 10 pack years of self-reported smoking exposure and an average of more or equal to 10 cigarettes/day
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky 70-100%)
• Total bilirubin less or equal to 2 \* upper limit of normal (ULN)
• Direct bilirubin less or equal to 2 \* ULN
• aspartate aminotransferase (AST)/(SGOT) less or equal to 2 \* ULN
• alanine aminotransferase (ALT)/(SGPT) less or equal to 2 \* ULN
• Alkaline phosphatase less or equal to 2 \* ULN
• If the participant is female, of childbearing potential and not lactating, she has a documented negative serum pregnancy test within 14 days prior to randomization

You may not qualify if:

• The participant has active cancer (excluding non-melanoma skin cancer)
• The participant has a history of curatively treated cancer with surgical therapy finished within 6 months prior to the Screening visit; or has had chemotherapy, cancer-related immunotherapy, hormonal therapy (other than Hormone replacement therapy (HRT) for menopause), or radiation therapy within 12 months of the screening visit
• The participant has a chronic inflammatory condition, including but not limited to, ulcerative colitis, Crohn's disease, rheumatoid arthritis, psoriasis, gout and pancreatitis
• The participant has an ongoing or active infection, including but not limited to HIV, pneumonia, urinary tract infection
• The participant has a history of nonsteroidal anti-inflammatory drugs (NSAIDs) use, including aspirin (low-dose aspirin also prohibited) and selective COX-2 inhibitors within the previous 4 weeks
• The participant has used zileuton or a leukotriene receptor antagonist within the previous 4 weeks
• The participant has a history of corticosteroid use (excluding topical nasal sprays and dermal application) within the last 6 weeks
• The participant has an acute or chronic kidney disorder
• The participant exhibits clinical evidence of active liver disease or history of chronic liver disease
• The participant has active cardiac disease, or a history of myocardial infarction, angina or coronary artery disease within the past 6 months
• The participant has a history of a cerebrovascular accident (CVA) or transient ischemic attack (TIA)
• The participant has a bleeding history
• The participant is taking drugs known to interact with zileuton or celecoxib, including theophylline, warfarin, propranolol, fluconazole or lithium
• The participant has received any investigational medication within 30 days of the screening visit or is scheduled to receive an investigational agent during the study
• The participant is pregnant or nursing; women must not be pregnant or lactating

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Weill Cornell Medical College in New York City, Cornell University

New York, New York, 10021, United States

Location

MD Anderson Cancer Center - Consortium Lead Organzation

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas (UT) MD Anderson Cancer Center Official Website

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking

Interventions

zileuton; Celecoxib

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Powel H. Brown, MD Anderson Phase I/II Prevention Consortium
• Organization: University of Texas (UT) MD Anderson Cancer

CR_Study_Registration@mdanderson.org

(713) 745-3672

Study Officials

• Powel Brown, MD

  University of Texas (UT) MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2009
• First Posted: November 26, 2009
• Study Start: May 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: March 1, 2013
• Last Updated: April 2, 2015
• Results First Posted: April 2, 2015

Record last verified: 2013-10

Locations

US (2)