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Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia

Phase 2
45 Years
74 Years
Not Enrolling
Lung Cancer, Precancerous Condition, Tobacco Use Disorder

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Trial Information

Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia



- To evaluate the efficacy and safety of Polyphenon E, a defined green tea catechin
extract, in current or former smokers with bronchial dysplasia and increased
inflammatory load as measured by C-reactive protein.


- To evaluate the ability of Polyphenon E to modulate other surrogate endpoint biomarkers
of oxidation stress, inflammation, aberrant methylation, cell cycle regulation,
apoptosis, oncogene/tumor suppressor gene expression, as well as phase I and II enzyme
regulation in biological samples from these patients.

- To establish a library of optical coherent tomography (OCT) images of the bronchial
epithelium with corresponding histopathology, nuclear morphometry, and other biomarker

- To assess the potential of OCT as a non-biopsy method for evaluating chemoprevention

OUTLINE: This is a multicenter study. Patients are stratified by gender. Patients are
randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral Polyphenon E twice daily for 3 months in the absence of
disease progression or unacceptable toxicity.

- Arm II: Patients receive a placebo twice daily for 3 months in the absence of disease
progression or unacceptable toxicity.

Patients undergo standard white-light bronchoscopy and fluorescence bronchoscopy with
optical coherence tomography (OCT) at baseline and at 3 months. During these procedures,
patients are evaluated using the Onco-LIFE clinical device, which digitally records OCT
images of abnormal areas or areas suspicious for intraepithelial neoplasia or invasive
carcinoma. Once these areas have been localized, patients are biopsied under fluorescence
bronchoscopy guidance to obtain both dysplastic bronchial epithelial tissue and normal
bronchial mucosa. Biopsy specimens are examined by immunostaining for tissue-based
biomarkers (i.e., Ki-67, cleaved caspase-3, p53, and VEGF). Patients also undergo oral
brushing, bronchial brushing, and bronchoalveolar lavage at baseline and at 3 months to
obtain bronchial epithelial cells for differential gene expression and methylation biomarker
studies (e.g., cDNA microarray analysis, polymerase chain reaction, and northern blotting).
Cytokines and other molecular biomarkers (i.e., C-reactive protein, surfactant protein D,
oxidized glutathione, interleukin [IL]-6, IL-13, and macrophage inflammatory protein-1
levels) are measured in blood and bronchoalveolar lavage fluid samples by enzyme-linked
immunoassay. Plasma EGCG levels are assessed by high-performance liquid chromatography.
Urine cotinine levels and exhaled carbon monoxide levels are also assessed.

After completion of study therapy, patients are followed at 1 month.

Inclusion Criteria


- Current or former smoker who has smoked ≥ 30 pack-years (i.e., 1 pack per day for ≥
30 years)

- A former smoker is defined as one who has stopped smoking for ≥ 1 year

- C-reactive protein level > 1.2 mg/L

- One or more areas of dysplasia with a surface diameter > 1.2 mm on autofluorescence

- No carcinoma in situ or invasive cancer on bronchoscopy

- No abnormal spiral chest CT scan suspicious of lung cancer


- ECOG performance status 0-1

- Willing to take Polyphenon E or placebo twice a day regularly

- Willing to undergo bronchoscopy and spiral chest CT scan

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Creatinine normal

- Bilirubin normal

- AST and ALT normal

- Alkaline phosphatase normal

- No chronic active hepatitis or liver cirrhosis

- No severe heart disease (e.g., unstable angina or chronic congestive heart failure)

- No ongoing gastric ulcer

- No acute bronchitis or pneumonia within the past month

- No known reaction to xylocaine, salbutamol, midazolam, or alfentanil

- No known allergy to green tea and/or corn starch, gelatin, or other nonmedicinal

- No medical condition, such as acute or chronic respiratory failure or bleeding
disorder, that, in the opinion of the investigator, could jeopardize patient safety
during study participation


- No concurrent consumption of > 7 cups of tea a week

- No other concurrent natural health products containing green tea compounds

- No concurrent antiarrhythmic agents

- No concurrent anticoagulants, such as warfarin or heparin

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Change in the severity of dysplasia (as defined by WHO criteria) in bronchial biopsy specimens as assessed at baseline and at 3 months

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Stephen Lam, MD

Investigator Role:

Study Chair

Investigator Affiliation:

British Columbia Cancer Agency


United States: Food and Drug Administration

Study ID:




Start Date:

October 2006

Completion Date:

July 2011

Related Keywords:

  • Lung Cancer
  • Precancerous Condition
  • Tobacco Use Disorder
  • non-small cell lung cancer
  • squamous lung dysplasia
  • tobacco use disorder
  • Lung Neoplasms
  • Precancerous Conditions
  • Tobacco Use Disorder