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Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Lung Carcinoma; Tobacco Use Disorder

Intervention: Aspirin (Drug); Laboratory Biomarker Analysis (Other); Placebo (Other); Placebo (Other); Zileuton (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Hsiao-Hui (Sherry) Chow, Principal Investigator, Affiliation: The University of Arizona Medical Center-University Campus

Summary

This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Smokers are at increased risk for developing lung and other cancers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers.

Clinical Details

Official title: Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Primary outcome: Changes in a smoking-related gene expression signature score in the nasal epithelium of current smokers after ASA and zileuton intervention

Secondary outcome:

Change in urinary LTE (4) levels

Change in urinary PGE-M levels

Changes in the metabolomics profile of the arachidonic acid pathway

Gender effect on smoking-related gene expression signature

Impact of ASA and zileuton on three lung cancer gene signatures (an 80-gene bronchial signature, a PI3K pathway gene signature and a nasal diagnostic gene signature)

Incidence of adverse events graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Whole-genome gene expression

Detailed description: PRIMARY OBJECTIVES: I. To analyze the impact of combined treatment of ASA (aspirin) and zileuton on smoking-related gene expression signature in the nasal epithelium in current smokers and to analyze any difference between the ASA and zileuton intervention and placebo control. SECONDARY OBJECTIVES: I. To assess the impact of ASA and zileuton on three lung cancer gene signatures (an 80- gene bronchial signature, a phosphatidylinositol 3-kinase (PI3K) pathway gene signature and a nasal diagnostic gene signature) and to compare this to placebo control. II. To measure urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) ( LTE[4]) levels in current smokers after ASA and zileuton. III. To assess the safety in current smokers of 12 week exposure to ASA and zileuton. IV. To evaluate a gender effect in the modulatory effects of ASA and zileuton on smoking related-gene expression signature. V. To explore the effect of ASA and zileuton on the metabolomics profile of the arachidonic acid pathway. VI. To explore, in a discovery-driven fashion, the effect of ASA and zileuton on whole-genome gene expression. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive aspirin orally (PO) once daily (QD) and zileuton PO twice daily (BID) for 12 weeks. ARM I: Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks. After completion of study treatment, patients are followed up for 2 weeks.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female current tobacco smokers with >= 20 pack years of self-reported smoking

exposure and an average use of >= 10 cigarettes/day

- Karnofsky >= 70%

- Leukocytes >= 3,000/microliter

- Absolute neutrophil count >= 1,500/microliter

- Hematocrit within normal institutional limits

- Platelets >= 150,000/microliter

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase

[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) within normal institutional limits

- Creatinine within normal institutional limits

- Prothrombin time (PT)/partial thromboplastin time (PTT) within normal institutional

limits

- Fertile subjects must use adequate contraception (abstinence, barrier methods, or

birth control pills) prior to study entry and for the duration of study participation; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

- Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging

if nodule follow-up has been completed or the study procedures would not interfere with nodule follow-up

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- History of allergic reaction to aspirin or attributed to compounds of similar

chemical or biologic composition to aspirin, including other nonsteroidal anti-inflammatory drugs (NSAIDs)

- Gastric intolerance attributable to ASA or NSAIDs

- History of gastric ulcer (with or without bleeding)

- Use of ASA or NSAIDs for more than 5 days per month within 3 months of enrollment

- Not willing or are unable to refrain from use of any non-study ASA, NSAIDs and

leukotriene antagonists during the study period

- Require chronic anticoagulation or anti-platelet therapy

- History of bleeding disorder or hemorrhagic stroke

- Chronic, current or recent (within the past three months) use of leukotriene

antagonists

- Chronic, current or recent (within the past three months) use of glucocorticoids

(systemic, topical and/or nasal sprays)

- History of chronic sinusitis or recent nasal polyps

- History of, or current, active or chronic liver disease even if transaminases have

normalized

- History of allergic reaction to zileuton or attributed to compounds of similar

chemical or biologic composition to zileuton

- Are taking drugs known to interact with zileuton, including theophylline, warfarin,

and propranolol

- Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a

day during the study period

- Pregnant or lactating women; breastfeeding should be discontinued if the mother is

treated with aspirin; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

- Participants may not be receiving any other investigational agents

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active

infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

- Have a known history of inability to absorb an oral agent

- Invasive cancer within the past five years except non-melanoma skin cancer

Locations and Contacts

The University of Arizona Medical Center-University Campus, Tucson, Arizona 85724, United States; Not yet recruiting
Linda L. Garland, Phone: 520-626-3434, Email: lgarland@azcc.arizona.edu
Linda L. Garland, Principal Investigator

University of California Davis Comprehensive Cancer Center, Sacramento, California 95817, United States; Not yet recruiting
Jun Yan, Phone: 530-752-5109, Email: junyang@ucdavis.edu
Jun Yan, Principal Investigator

Boston University School of Medicine, Boston, Massachusetts 02118, United States; Not yet recruiting
Avrum Spira, Phone: 617-414-6960, Email: aspira@bu.edu
Avrum Spira, Principal Investigator

Additional Information

Starting date: April 2015
Last updated: May 6, 2015

Page last updated: August 23, 2015

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