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

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)

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer Prevention
• Intervention / Treatment: Other: placebo; Dietary supplement: green tea; Drug: Polyphenon E

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center at University of Arizona Health Sciences Center
    • Tucson, Arizona, United States, 85258
      • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Green Tea; Patients receive green tea beverage and placebo capsules for 6 months.	Dietary supplement: green tea; Given orally
Experimental: Polyphenon E; Patients receive placebo beverage and Polyphenon E capsules daily for 6 months.	Drug: Polyphenon E; Given orally
Placebo Comparator: Placebo; Patients receive placebo beverage and placebo capsules daily for 6 months.	Other: placebo; Given orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sherry Chow
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Iman Hakim, MD, PhD, MPH, University of Arizona

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: August 10, 2006
• First Submitted That Met QC Criteria: August 10, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Estimate): November 28, 2013
• Last Update Submitted That Met QC Criteria: September 27, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: lung cancer; prevention; green tea; former smokers
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: CDR0000487501; P30CA023074 (U.S. NIH Grant/Contract); U01CA101204 (U.S. NIH Grant/Contract); UARIZ-HSC-0353