Green Tea or Polyphenon E in Preventing Lung Cancer in Former Smokers With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. The use of green tea or polyphenon E may prevent cancer from forming in former smokers with chronic obstructive pulmonary disease. PURPOSE: This randomized phase II trial is studying how well green tea or polyphenon E work in preventing lung cancer in former smokers with chronic obstructive pulmonary disease.

Detailed Description
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OBJECTIVES: Primary Evaluate the effects of high-level oral consumption of defined green tea (four 12-oz servings/day) or polyphenon E capsules (4 capsules/day) on markers of cellular oxidative damage, as measured by 8-hydroxydeoxyguanosine (8-OHdG) and 8-F_2-isoprostanes (8-epi-PGF2) in former smokers with chronic obstructive pulmonary disease. Secondary Evaluate the effects of high-level oral consumption of defined green tea or polyphenon E capsules on body antioxidant status (carotenoids, vitamins A and E, ascorbic acid [vitamin C] and antioxidant enzymes [catalase and glutathione peroxidase]) in blood in these patients. Evaluate the effects of high-level oral consumption of defined green tea or polyphenon E capsules on gene expression of markers of proliferation and apoptosis in induced sputum in these patients. Tertiary Evaluate the effects of high-level oral consumption of defined green tea or polyphenon E capsules on lung function in these patients. Evaluate the relative adherence to use of green tea beverage vs polyphenon E capsules in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to gender and inhaled steroid usage (yes vs no). All patients receive placebo tea beverage and placebo capsules 4 times a day for 2 weeks. Patients are randomized to 1 of 3 treatment arms after successful completion of the 2-week period. Arm I (green tea beverage): Patients receive oral green tea beverage and oral polyphenon E placebo daily for 6 months. Arm II (green tea capsule [polyphenon E]): Patients receive oral green tea beverage placebo and oral polyphenon E daily for 6 months. Arm III (placebo): Patients receive oral green tea beverage placebo and oral polyphenon E placebo daily for 6 months. Patients undergo blood, urine, exhaled breath condensate (EBC), induced sputum, and buccal cell collection at baseline and periodically during study for biomarker/laboratory analysis. Blood samples are analyzed for 8-hydroxydeoxyguanosine (8-OHdG), glutathione peroxidase, and catalase. Urine is examined for F_2-isoprostanes, 8-OHdG, and tea polyphenols. Induced sputum broncho-epithelial cells are analyzed for gene expression of genes implicated in cellular growth and apoptotic pathway via reverse transcriptase-polymerase chain reaction. EBC samples are examined for F_2-isoprostane levels. Buccal cells are stored for future analysis. PROJECTED ACCRUAL: A total of 195 patients will be accrued for this study.

Official Title
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Chemoprevention of Lung Carcinogenesis Using Green Tea: Phase IIb Randomized, Double-Blinded, Placebo Controlled Trial of Green Tea and Polyphenon E in Former Smokers With Chronic Obstructive Lung Disease (COPD)

Conditions
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Lung Cancer Prevention

Intervention / Treatment
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* Dietary Supplement: green tea
* Drug: Polyphenon E
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of chronic obstructive pulmonary disease FEV_1/FVC ≤ 78 History of smoking ≥ 1 pack daily for 30 years OR 2 packs daily for 15 years Stopped smoking for ≥ 1 year No previously diagnosed bronchiectasis No history of > 1 acute emphysema exacerbation within the past 3 months PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC ≥ 3,500/mm³ Platelet count > 130,000/mm³ Hemoglobin ≥ 11 g/dL (female) or 12 g/dL (male) AST and ALT normal Bilirubin ≤ 1.5 mg/dL (unless Gilbert's disease present) Creatinine ≤ 1.5 mg/dL Alkaline phosphatase ≤ 2 times upper limit of normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No invasive cancer within the past 5 years Able and willing to consume caffeinated beverages Able to produce induced sputum Able to perform forced expiratory maneuver during spirometry testing No immunosuppression by virtue of medication or disease including, but no limited to, any of the following: Organ transplantation Liver or kidney failure Autoimmune diseases Oral steroids Chemotherapy No serious concurrent illness that could preclude study compliance, such as uncontrolled high blood pressure, heart disease, or poorly controlled diabetes No myocardial infarction within the past 6 weeks PRIOR CONCURRENT THERAPY: At least 2 weeks since prior and no concurrent dietary supplements or herbal products, including any of the following: Herbal tea Ginkgo biloba > 60 mg/day Melatonin > 3 mg/day Echinacea > 300 mg/day Hypericum perforatum (St. John's wort) > 300 mg/day DHEA mustard > 5 mg/day At least 2 weeks since prior and no concurrent nontrial tea or tea products More than 3 weeks since prior chest or abdominal surgery More than 3 months since prior participation in chemoprevention or clinical intervention trials At least 3 months since prior and no concurrent megadoses of vitamins, defined as > 4,000 IU of vitamin A, 400 IU of vitamin E, 400 IU of cholecalciferol (vitamin D), 60 μg of selenium, or 1,000 mg of ascorbic acid (vitamin C) per day No regular consumption of ≥ 6 cups or glasses of tea per week No concurrent nontrial caffeine at > 1 serving/day (1 serving defined as 12 oz of regular soda or 8 oz of coffee) No concurrent participation in another interventional clinical trial

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Green Tea<br>Patients receive green tea beverage and placebo capsules for 6 months. | Dietary Supplement: green tea<br>* Given orally<br>|
| Experimental: Polyphenon E<br>Patients receive placebo beverage and Polyphenon E capsules daily for 6 months. | Drug: Polyphenon E<br>* Given orally<br>|
| Placebo Comparator: Placebo<br>Patients receive placebo beverage and placebo capsules 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 |
| --- | --- | --- |
| Change in Urinary 8-hydroxydeoxyguanosine Levels | the urinary concentrations of 8-hydroxydeoxyguanosine were normalized by the urinary creatinine concentrations to correct for variations in urine dilution/production and the change in urinary 8-hydroxydeoxyguanosine levels was calculated as the 6 months levels minus the baseline levels | Baseline and 6 months | 
| Change in Urinary 8-F2-isoprostanes Levels | the urinary concentrations of 8-F2-isoprostanes were normalized by the urinary creatinine concentrations to correct for variations in urine dilution/production and the change in urinary 8-F2-isoprostanes levels was calculated as 6 months levels minus baseline levels | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, prevention, green tea, former smokers