Green Tea Extract in Preventing Cancer in Former and Current Heavy Smokers With Abnormal Sputum

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. Green tea extract may keep cancer from forming. PURPOSE: This randomized phase II trial is studying green tea extract in preventing cancer in former and current heavy smokers with abnormal sputum.

Detailed Description
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OBJECTIVES: Evaluate the efficacy and safety of defined green tea catechin extract (polyphenon E) in former smokers with abnormal sputum score using stringent, newly developed response criteria of combined nuclear morphometry and malignancy-associated changes as the primary surrogate endpoint. Evaluate if polyphenon E can modulate other surrogate endpoint biomarkers of aberrant methylation, cell cycle regulation, apoptosis, oncogene/tumor suppressor gene expression, as well as phase I and II enzyme regulation. Establish a library of in-vivo confocal micro-endoscopy and optical coherent tomography images of the bronchial epithelium with corresponding histopathology, nuclear morphometry, and other biomarker information to assess the potential of confocal micro-endoscopy as a non-biopsy method to assess the effect of chemoprevention agents. OUTLINE: This is an open label, part 1 study followed by a randomized, double-blind, part 2 study. Part 1 (completed March 22, 2006): Patients receive oral defined green tea catechin extract twice daily in months 1 and 2 and inhaled budesonide twice daily in month 2. Patients undergo autofluorescence bronchoscopy with biopsies, oral and bronchial brushing, and bronchoalveolar lavage at the end of months 1 and 2. Part 2: Patients are stratified by gender and randomized to 1 of 2 treatment arms. Arm I: Patients receive oral defined green tea catechin extract twice daily for 6 months. Arm II: Patients receive oral placebo twice daily for 6 months. Patients who have progressive or stable disease at 6 months may receive open-label defined green tea catechin extract. Patients undergo autofluorescence bronchoscopy with biopsies, oral and bronchial brushing, and bronchoalveolar lavage at the end of months 6 and 12. Blood samples are collected periodically for biomarker studies. After completion of study therapy, patients are followed periodically for 6 months.

Official Title
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Phase II Trial of Polyphenon E in Former Smokers With Abnormal Sputa

Conditions
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Lung Cancer, Tobacco Use Disorder

Intervention / Treatment
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* Drug: defined green tea catechin extract
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Current smokers who have smoked at least 30 pack-years (e.g., 1 pack per day for 30 years or more) (part 1; completed March 22, 2006) Former smokers who have smoked at least 30 pack-years (part 2) A former smoker is defined as one who has stopped smoking for one or more years Abnormal sputum score ≥ 0.25 by computer-assisted image analysis Exhaled carbon monoxide level < 5 ppm (part 2 ) Willing to take defined green tea catechin extract/placebo twice a day regularly No evidence of overt lung cancer No carcinoma in situ or invasive cancer on bronchoscopy or abnormal spiral chest CT suspicious of lung cancer PATIENT CHARACTERISTICS: Inclusion criteria: ECOG performance status 0-1 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Creatinine normal Bilirubin normal AST and ALT normal Alkaline phosphatase normal Exclusion criteria: Chronic active hepatitis/liver cirrhosis Severe heart disease (e.g., unstable angina, chronic congestive heart failure, use of antiarrhythmic agents) Ongoing gastric ulcer Acute bronchitis or pneumonia within one month Known reaction to lidocaine, albuterol sulfate, midazolam hydrochloride, and/or alfentanil hydrochloride Known allergy to green tea and/or corn starch, gelatin, or other nonmedicinal ingredients Any medical condition, such as acute or chronic respiratory failure or bleeding disorder that, in the opinion of the investigator, could jeopardize the patient's safety during participation in the study Unwilling to have a bronchoscopy Unwilling to have a spiral chest CT PRIOR CONCURRENT THERAPY: No more than 5 cups of tea a week No concurrent anticoagulant treatment such as warfarin or heparin No use of other natural health products containing green tea compounds

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral defined green tea catechin extract twice daily for 6 months. | Drug: defined green tea catechin extract<br>* Given orally<br>|
| Placebo Comparator: Arm II<br>Patients receive oral placebo twice daily for 6 months. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in oncogene/tumor suppression gene expression (part 1; completed March 22, 2006) |  | 36 months | 
| Phase I and II enzyme regulation by Affymetrix chip analysis in bronchial brush cells (part 1) |  | 60 months | 
| C-reactive protein level in plasma before treatment and 1 and 2 months after treatment (part 1) |  | 60 months | 
| Quantitative sputum score by image analysis before and 6 months after treatment (part 2) |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pathology grade of bronchial biopsies (part 2) |  | 36 months | 
| Morphometric index of bronchial biopsies and bronchoalveolar lavage cells (BAL) (part 2) |  | 36 months | 
| Methylation markers in sputa and BAL cells (part 2) |  | 60 months | 
| Ki-67 expression (part 2) |  | 60 months | 
| Cleaved caspase 3, p53, and VEGF assays in bronchial biopsies (part 2) |  | 60 months | 
| Oncogene and tumor suppression gene expression (part 2) |  | 60 months | 
| Phase I and II enzyme regulation by Affymetrix chip analysis of RNA from bronchial brush cells (part 2) |  | 60 months | 
| C-reactive protein levels in plasma before treatment, and 6 months after treatment (part 2) |  | 36 months | 
| Resolution or progression of non-calcified lung nodules on spiral CT (part 2) |  | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, small cell lung cancer, tobacco use disorder