Green Tea Extract in Treating Current or Former Smokers With Bronchial Dysplasia

This study has been terminated.
(Slow recruitment)
Sponsor:
Collaborators:
University of Cincinnati
Information provided by (Responsible Party):
British Columbia Cancer Agency
ClinicalTrials.gov Identifier:
NCT00611650
First received: February 8, 2008
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of Polyphenon E, a substance found in green tea, may keep cancer from forming in current or former smokers with bronchial dysplasia.

PURPOSE: This randomized phase II trial is studying the side effects and how well green tea extract works in treating current or former smokers with bronchial dysplasia.


Condition Intervention Phase
Lung Cancer
Precancerous Condition
Tobacco Use Disorder
Drug: defined green tea catechin extract
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia

Resource links provided by NLM:


Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:
  • Change in the severity of dysplasia (as defined by WHO criteria) in bronchial biopsy specimens as assessed at baseline and at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in the morphometric index in bronchial biopsy specimens as assessed at baseline and at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Change in the concentrations (or grades) of Ki-67, p53, cleaved caspase-3, and VEGF in bronchial biopsy specimens as assessed by immunostaining at baseline and at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Methylation biomarkers in bronchoalveolar lavage (BAL) cells as assessed at baseline and at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Oncogene/ tumor suppressor gene expression in bronchial brush cells as assessed by cDNA microarray analysis at baseline and at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Phase I and II enzyme regulation in bronchial brush cells as assessed by Affymetrix microarray analysis at baseline and at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Change in C-reactive protein levels in plasma as assessed by enzyme-linked immunoassay (ELISA) at baseline and then monthly for 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Volumetric measurement of CT-detected lung nodules at baseline and then every 3-12 months for up to 24 months, depending on the size of the nodule [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Change in the concentrations (or grades) of surfactant protein D, oxidized glutathione, interleukin (IL)-6, IL-13, and MPIF-1 in plasma and BAL cells as assessed by ELISA at baseline and at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: October 2006
Study Completion Date: July 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral Polyphenon E twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
Drug: defined green tea catechin extract
Given orally
Placebo Comparator: Arm II
Patients receive a placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
Other: placebo
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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 information.
  • To assess the potential of OCT as a non-biopsy method for evaluating chemoprevention agents.

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.

  Eligibility

Ages Eligible for Study:   45 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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 bronchoscopy
  • No carcinoma in situ or invasive cancer on bronchoscopy
  • No abnormal spiral chest CT scan suspicious of lung cancer

PATIENT CHARACTERISTICS:

  • 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 ingredients
  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00611650

Locations
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Sponsors and Collaborators
British Columbia Cancer Agency
University of Cincinnati
Investigators
Study Chair: Stephen Lam, MD British Columbia Cancer Agency
  More Information

No publications provided

Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT00611650     History of Changes
Other Study ID Numbers: CDR0000578224, P01CA096964, BCCA-H07-02401, H07-02401
Study First Received: February 8, 2008
Last Updated: March 7, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by British Columbia Cancer Agency:
non-small cell lung cancer
squamous lung dysplasia
tobacco use disorder

Additional relevant MeSH terms:
Tobacco Use Disorder
Lung Neoplasms
Precancerous Conditions
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014