Green Tea Extract in Treating Current or Former Smokers With Bronchial Dysplasia

Phase 2

Terminated

• Conditions: Lung Cancer; Precancerous Condition; Tobacco Use Disorder
• Interventions: Drug: defined green tea catechin extract; Other: placebo

• Registration Number: NCT00611650
• Lead Sponsor: British Columbia Cancer Agency

Brief Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of Polyphenon E, a substance found in green tea, may keep cancer from forming in current or former smokers with bronchial dysplasia.

PURPOSE: This randomized phase II trial is studying the side effects and how well green tea extract works in treating current or former smokers with bronchial dysplasia.

Detailed Description

OBJECTIVES:

Primary

* To evaluate the efficacy and safety of Polyphenon E, a defined green tea catechin extract, in current or former smokers with bronchial dysplasia and increased inflammatory load as measured by C-reactive protein.

Secondary

* To evaluate the ability of Polyphenon E to modulate other surrogate endpoint biomarkers of oxidation stress, inflammation, aberrant methylation, cell cycle regulation, apoptosis, oncogene/tumor suppressor gene expression, as well as phase I and II enzyme regulation in biological samples from these patients.

* To establish a library of optical coherent tomography (OCT) images of the bronchial epithelium with corresponding histopathology, nuclear morphometry, and other biomarker information.

* To assess the potential of OCT as a non-biopsy method for evaluating chemoprevention agents.

OUTLINE: This is a multicenter study. Patients are stratified by gender. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral Polyphenon E twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive a placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

Patients undergo standard white-light bronchoscopy and fluorescence bronchoscopy with optical coherence tomography (OCT) at baseline and at 3 months. During these procedures, patients are evaluated using the Onco-LIFE clinical device, which digitally records OCT images of abnormal areas or areas suspicious for intraepithelial neoplasia or invasive carcinoma. Once these areas have been localized, patients are biopsied under fluorescence bronchoscopy guidance to obtain both dysplastic bronchial epithelial tissue and normal bronchial mucosa. Biopsy specimens are examined by immunostaining for tissue-based biomarkers (i.e., Ki-67, cleaved caspase-3, p53, and VEGF). Patients also undergo oral brushing, bronchial brushing, and bronchoalveolar lavage at baseline and at 3 months to obtain bronchial epithelial cells for differential gene expression and methylation biomarker studies (e.g., cDNA microarray analysis, polymerase chain reaction, and northern blotting). Cytokines and other molecular biomarkers (i.e., C-reactive protein, surfactant protein D, oxidized glutathione, interleukin \[IL\]-6, IL-13, and macrophage inflammatory protein-1 levels) are measured in blood and bronchoalveolar lavage fluid samples by enzyme-linked immunoassay. Plasma EGCG levels are assessed by high-performance liquid chromatography. Urine cotinine levels and exhaled carbon monoxide levels are also assessed.

After completion of study therapy, patients are followed at 1 month.

Study Timeline

• Study Start: 2006-10
• Study First Submitted: 2008-02-08
• Study First Submitted QC: 2008-02-08
• Study First Posted: 2008-02-11
• Primary Completion: 2011-06
• Study Completion: 2011-07
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-07
• Last Update Posted: 2012-03-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	defined green tea catechin extract	Patients receive oral Polyphenon E twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
Arm II	placebo	Patients receive a placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Change in the severity of dysplasia (as defined by WHO criteria) in bronchial biopsy specimens as assessed at baseline and at 3 months	3 months

Secondary Outcome Measures

Name	Time	Method
Change in the morphometric index in bronchial biopsy specimens as assessed at baseline and at 3 months	3 months
Change in the concentrations (or grades) of Ki-67, p53, cleaved caspase-3, and VEGF in bronchial biopsy specimens as assessed by immunostaining at baseline and at 3 months	3 months
Methylation biomarkers in bronchoalveolar lavage (BAL) cells as assessed at baseline and at 3 months	3 months
Oncogene/ tumor suppressor gene expression in bronchial brush cells as assessed by cDNA microarray analysis at baseline and at 3 months	3 months
Phase I and II enzyme regulation in bronchial brush cells as assessed by Affymetrix microarray analysis at baseline and at 3 months	3 months
Change in C-reactive protein levels in plasma as assessed by enzyme-linked immunoassay (ELISA) at baseline and then monthly for 3 months	3 months
Volumetric measurement of CT-detected lung nodules at baseline and then every 3-12 months for up to 24 months, depending on the size of the nodule	24 months
Change in the concentrations (or grades) of surfactant protein D, oxidized glutathione, interleukin (IL)-6, IL-13, and MPIF-1 in plasma and BAL cells as assessed by ELISA at baseline and at 3 months	3 months

Trial Locations

Locations (1)

British Columbia Cancer Agency - Vancouver Cancer Centre; 🇨🇦 Vancouver, British Columbia, Canada