Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Prevention Active 40 to 80 NCI UARIZ-HSC-0353 U01-CA-101204, NCT00363805

Objectives

Primary

1. 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-F₂-isoprostanes (8-epi-PGF2) in former smokers with chronic obstructive pulmonary disease.

Secondary

1. 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.
2. Evaluate the effects of high-level oral consumption of defined green tea or polyphenon E capsules on gene expression of markers of proliferation (epidermal growth factor receptor [EGFR], proliferating cell nuclear antigen [PCNA], JUN, FOS, and Ki-67) and apoptosis (bcl-2 and caspase 3) in induced sputum in these patients.

Tertiary

1. Evaluate the effects of high-level oral consumption of defined green tea or polyphenon E capsules on lung function, in terms of FEV₁ and FVC improvement, in these patients.
2. Evaluate the relative adherence to use of green tea beverage vs polyphenon E capsules in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of chronic obstructive pulmonary disease
  • FEV₁/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

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

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

Expected Enrollment

A total of 195 patients will be accrued for this study.

Outcomes

Biomarkers of cellular oxidative damage
Clinical improvement in pulmonary function

Modulation of gene expression in induced sputum

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 F₂-isoprostanes, 8-OHdG, and tea polyphenols. Induced sputum bronchoepithelial cells are analyzed for gene expression of genes implicated in cellular growth and apoptotic pathway (i.e., epidermal growth factor receptor [EGFR], proliferating cell nuclear antigen [PCNA], JUN, FOS, Ki-67, bcl-2, and caspase 3) via reverse transcriptase-polymerase chain reaction. EBC samples are examined for F₂-isoprostane levels. Buccal cells are stored for future analysis.

Trial Contact Information

Trial Lead Organizations

Arizona Cancer Center at University of Arizona Health Sciences Center

Iman Hakim, MD, PhD, MPH, Principal investigator		Ph: 520-626-5355; 800-622-2673 Email: ihakim@azcc.arizona.edu

U.S.A.
Arizona
	Tucson
	Arizona Cancer Center at University of Arizona Health Sciences Center
		Clinical Trials Office - Arizona Cancer Center at University of Arizona Health Sciences Center	Ph:  520-626-9008

Registry Information
Official Title		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)
Trial Start Date		2004-05-01
Trial Completion Date		2009-03-15 (estimated)
Registered in ClinicalTrials.gov		NCT00363805
Date Submitted to PDQ		2006-05-30
Information Last Verified		2008-10-24
NCI Grant/Contract Number		CA101204, CA23074