Substance Related Disorders

Behaviors and Mental Disorders

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Tobacco Use Disorder

Lung Diseases

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorders

Psychotic Disorders

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Respiratory System Agents

Other Dietary Supplements

Celecoxib

Zileuton

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Leukotriene Antagonists

Hormones

Hormone Antagonists

Arachidonic Acid

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

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

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

200 mg twice daily given orally for 6 days

laboratory biomarker analysis

Powel Brown, MD

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

PRIMARY OBJECTIVES:

I. To determine whether short-term administration of zileuton, a 5-lipoxygenase (5-LO) inhibitor, in current smokers will suppress the formation of urinary leukotriene E4 (LTE4) and shunt arachidonic acid into the cyclooxygenase (COX) pathway, resulting in elevated urinary prostaglandin E-metabolite (PGE-M).

SECONDARY OBJECTIVES:

I. To determine whether short-term co-administration of celecoxib, a selective COX-2 inhibitor, and zileuton suppresses levels of both urinary LTE4 and PGE-M in current smokers.

II. To evaluate the association between baseline levels of urinary LTE4 and magnitude of the arachidonic acid shunt induced by zileuton.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive zileuton orally (PO) twice daily (BID) on days 1-6.

ARM II: Patients receive zileuton as in Arm I and celecoxib PO BID on days 1-6.

Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers

Modulation of Arachidonic Acid Metabolism by Chemopreventive Agents in Smokers

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).

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).

Proportion of cases with a post-treatment increase in urinary PGE-M levels by comparing those treated with Zileuton and Celecoxib combined therapy compared to those treated with Zileuton alone. Pre/postchange in levels (Increase) derived from baseline level to Day 6 +/- 1 day. Differences in baseline levels between 2 treatment arms were examined using the Wilcoxon rank-sum test.

National Cancer Institute (NCI)

Common Toxicity reporting for the study began with Common Toxicity Criteria for Adverse Effects (CTCAE) version 3.0 and completed with CTCAE version 4.0. Reporting has been combined in the provided tables.

Arm I: Zileuton

Arm II: Zileuton and Celecoxib

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Number of cigarette packs smoked annually; Measure includes the 70 compliant participants only.

Smoking (Packs per Year)

Prostaglandin E metabolite (PGE-M) levels via creatinine (Cr) in the urine measured by a chemical assay. Baseline measure includes the 70 compliant study participants only.

Baseline PGE-M (ng/mg Cr)

Leukotriene E4 (LTE4) levels via creatinine (Cr) in the urine measured by a chemical assay. Baseline measure includes the 70 compliant study participants only.

Baseline LTE4 (pg/mg CR)

Female

Male

Measure includes the 70 compliant study participants only.

Gender, Male/Female: Compliant Participants

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

Unknown or Not Reported

Baseline measure includes the 70 compliant study participants only.

Race, Compliant Participants

Age, Continuous, Compliant Participants

Of the 80 participants treated three (3) were lost to follow up leaving 77 who completed treatment, and of those reflected as a subset are the 70 compliant participants who completed treatment.

Dr. Powel H. Brown, MD Anderson Phase I/II Prevention Consortium

Pre PGE-M Levels

Post PGE-M Levels

Seventy-seven subjects completed the entire study with seven of those excluded from analysis as non-compliant (study medications were undetectable). Urine of two participants contained interfering substances thus were excluded from PGE-M related analysis.

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

Pre LTE4 levels

Post LTE4 levels

Seventy-seven subjects completed the entire study, three withdrew for personal reasons. Seven of those participants were excluded from analysis as non-compliant (study medications were undetectable).

Median Urinary LTE4 Levels (Pre and Post Treatment)

Analysis includes only number of participants in each treatment arm with post-treatment increase in urinary PGE-M levels as measured from baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers	NCT01021215	Tobacco Use Dis...	Zileuton Celecoxib laboratory biom...	18 Years -	National Cancer Institute (NCI)
Zileuton With or Without Celecoxib As Chemopreventive Agents in Smokers	NCT01021215	Tobacco Use Dis...	Zileuton Celecoxib laboratory biom...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for zyflo cr

Every month we try and update this database with for zyflo cr cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for zyflo cr

Every month we try and update this database with for zyflo cr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for zyflo cr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.