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

Sponsor

British Columbia Cancer Agency (Other)

Overall Status

Terminated

CT.gov ID

NCT00611650

Collaborator

National Cancer Institute (NCI) (NIH), University of Cincinnati (Other)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer Precancerous Condition Tobacco Use Disorder	Drug: defined green tea catechin extract Other: placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia

Study Start Date :

Oct 1, 2006

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral Polyphenon E twice daily for 3 months in the absence of disease progression or unacceptable toxicity.	Drug: defined green tea catechin extract Given orally
Placebo Comparator: Arm II Patients receive a placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.	Other: placebo Given orally

Arm

Intervention/Treatment

Experimental: Arm I

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

Drug: defined green tea catechin extract

Given orally

Placebo Comparator: Arm II

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

Other: placebo

Given orally

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Current or former smoker who has smoked ≥ 30 pack-years (i.e., 1 pack per day for ≥ 30 years)
A former smoker is defined as one who has stopped smoking for ≥ 1 year
C-reactive protein level > 1.2 mg/L
One or more areas of dysplasia with a surface diameter > 1.2 mm on autofluorescence bronchoscopy
No carcinoma in situ or invasive cancer on bronchoscopy
No abnormal spiral chest CT scan suspicious of lung cancer

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Willing to take Polyphenon E or placebo twice a day regularly
Willing to undergo bronchoscopy and spiral chest CT scan
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Creatinine normal
Bilirubin normal
AST and ALT normal
Alkaline phosphatase normal
No chronic active hepatitis or liver cirrhosis
No severe heart disease (e.g., unstable angina or chronic congestive heart failure)
No ongoing gastric ulcer
No acute bronchitis or pneumonia within the past month
No known reaction to xylocaine, salbutamol, midazolam, or alfentanil
No known allergy to green tea and/or corn starch, gelatin, or other nonmedicinal ingredients
No medical condition, such as acute or chronic respiratory failure or bleeding disorder, that, in the opinion of the investigator, could jeopardize patient safety during study participation