Green Tea Extract in Treating Current or Former Smokers With Bronchial Dysplasia
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|ClinicalTrials.gov Identifier: NCT00611650|
Recruitment Status : Terminated (Slow recruitment)
First Posted : February 11, 2008
Last Update Posted : March 9, 2012
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|
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia|
|Study Start Date :||October 2006|
|Primary Completion Date :||June 2011|
|Study Completion Date :||July 2011|
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
Placebo Comparator: Arm II
Patients receive a placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
- Change in the severity of dysplasia (as defined by WHO criteria) in bronchial biopsy specimens as assessed at baseline and at 3 months [ Time Frame: 3 months ]
- Change in the morphometric index in bronchial biopsy specimens as assessed at baseline and at 3 months [ Time Frame: 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 [ Time Frame: 3 months ]
- Methylation biomarkers in bronchoalveolar lavage (BAL) cells as assessed at baseline and at 3 months [ Time Frame: 3 months ]
- Oncogene/ tumor suppressor gene expression in bronchial brush cells as assessed by cDNA microarray analysis at baseline and at 3 months [ Time Frame: 3 months ]
- Phase I and II enzyme regulation in bronchial brush cells as assessed by Affymetrix microarray analysis at baseline and at 3 months [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 3 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00611650
|Canada, British Columbia|
|British Columbia Cancer Agency - Vancouver Cancer Centre|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Study Chair:||Stephen Lam, MD||British Columbia Cancer Agency|