Clinical trial NCT00363805: Green Tea or Polyphenon E in Preventing Lung Cancer in Former Smokers With Chronic Obstructive Pulmonary Disease
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer Prevention
Keywords: lung cancer
prevention
green tea
former smokers
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-08-15
Enrollment: 178
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Urinary 8-hydroxydeoxyguanosine Levels
timeFrame: Baseline and 6 months
measure: Change in Urinary 8-F2-isoprostanes Levels
timeFrame: Baseline and 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
state: Arizona
city: Tucson
country: United States
facility: Veterans Affairs Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
Study officials:
affiliation: University of Arizona
name: Iman Hakim, MD, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References: