Green Tea Extract in Preventing Cancer in Former and Current Heavy Smokers With Abnormal Sputum

This study has been completed.
Sponsor:
Collaborators:
University of Cincinnati
Information provided by (Responsible Party):
British Columbia Cancer Agency
ClinicalTrials.gov Identifier:
NCT00573885
First received: December 13, 2007
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. Green tea extract may keep cancer from forming.

PURPOSE: This randomized phase II trial is studying green tea extract in preventing cancer in former and current heavy smokers with abnormal sputum.


Condition Intervention Phase
Lung Cancer
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: Open Label
Primary Purpose: Prevention
Official Title: Phase II Trial of Polyphenon E in Former Smokers With Abnormal Sputa

Resource links provided by NLM:


Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:
  • Changes in oncogene/tumor suppression gene expression (part 1; completed March 22, 2006) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Phase I and II enzyme regulation by Affymetrix chip analysis in bronchial brush cells (part 1) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • C-reactive protein level in plasma before treatment and 1 and 2 months after treatment (part 1) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Quantitative sputum score by image analysis before and 6 months after treatment (part 2) [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in pathology grade of bronchial biopsies (part 2) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Morphometric index of bronchial biopsies and bronchoalveolar lavage cells (BAL) (part 2) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Methylation markers in sputa and BAL cells (part 2) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Ki-67 expression (part 2) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Cleaved caspase 3, p53, and VEGF assays in bronchial biopsies (part 2) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Oncogene and tumor suppression gene expression (part 2) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • Phase I and II enzyme regulation by Affymetrix chip analysis of RNA from bronchial brush cells (part 2) [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • C-reactive protein levels in plasma before treatment, and 6 months after treatment (part 2) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Resolution or progression of non-calcified lung nodules on spiral CT (part 2) [ Time Frame: 60 months ] [ Designated as safety issue: No ]

Enrollment: 53
Study Start Date: January 2008
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral defined green tea catechin extract twice daily for 6 months.
Drug: defined green tea catechin extract
Given orally
Placebo Comparator: Arm II
Patients receive oral placebo twice daily for 6 months.
Other: placebo
Given orally

Detailed Description:

OBJECTIVES:

  • Evaluate the efficacy and safety of defined green tea catechin extract (polyphenon E) in former smokers with abnormal sputum score using stringent, newly developed response criteria of combined nuclear morphometry and malignancy-associated changes as the primary surrogate endpoint.
  • Evaluate if polyphenon E can modulate other surrogate endpoint biomarkers of aberrant methylation, cell cycle regulation, apoptosis, oncogene/tumor suppressor gene expression, as well as phase I and II enzyme regulation.
  • Establish a library of in-vivo confocal micro-endoscopy and optical coherent tomography images of the bronchial epithelium with corresponding histopathology, nuclear morphometry, and other biomarker information to assess the potential of confocal micro-endoscopy as a non-biopsy method to assess the effect of chemoprevention agents.

OUTLINE: This is an open label, part 1 study followed by a randomized, double-blind, part 2 study.

  • Part 1 (completed March 22, 2006): Patients receive oral defined green tea catechin extract twice daily in months 1 and 2 and inhaled budesonide twice daily in month 2.

Patients undergo autofluorescence bronchoscopy with biopsies, oral and bronchial brushing, and bronchoalveolar lavage at the end of months 1 and 2.

  • Part 2: Patients are stratified by gender and randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive oral defined green tea catechin extract twice daily for 6 months.
    • Arm II: Patients receive oral placebo twice daily for 6 months. Patients who have progressive or stable disease at 6 months may receive open-label defined green tea catechin extract.

Patients undergo autofluorescence bronchoscopy with biopsies, oral and bronchial brushing, and bronchoalveolar lavage at the end of months 6 and 12.

Blood samples are collected periodically for biomarker studies. After completion of study therapy, patients are followed periodically for 6 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Current smokers who have smoked at least 30 pack-years (e.g., 1 pack per day for 30 years or more) (part 1; completed March 22, 2006)
  • Former smokers who have smoked at least 30 pack-years (part 2)

    • A former smoker is defined as one who has stopped smoking for one or more years
  • Abnormal sputum score ≥ 0.25 by computer-assisted image analysis
  • Exhaled carbon monoxide level < 5 ppm (part 2 )
  • Willing to take defined green tea catechin extract/placebo twice a day regularly
  • No evidence of overt lung cancer

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

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0-1
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Creatinine normal
  • Bilirubin normal
  • AST and ALT normal
  • Alkaline phosphatase normal

Exclusion criteria:

  • Chronic active hepatitis/liver cirrhosis
  • Severe heart disease (e.g., unstable angina, chronic congestive heart failure, use of antiarrhythmic agents)
  • Ongoing gastric ulcer
  • Acute bronchitis or pneumonia within one month
  • Known reaction to lidocaine, albuterol sulfate, midazolam hydrochloride, and/or alfentanil hydrochloride
  • Known allergy to green tea and/or corn starch, gelatin, or other nonmedicinal ingredients
  • Any medical condition, such as acute or chronic respiratory failure or bleeding disorder that, in the opinion of the investigator, could jeopardize the patient's safety during participation in the study
  • Unwilling to have a bronchoscopy
  • Unwilling to have a spiral chest CT

PRIOR CONCURRENT THERAPY:

  • No more than 5 cups of tea a week
  • No concurrent anticoagulant treatment such as warfarin or heparin
  • No use of other natural health products containing green tea compounds
  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: NCT00573885

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

Additional Information:
No publications provided

Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT00573885     History of Changes
Other Study ID Numbers: CDR0000578191, P01CA096964, BCCA-H03-61083, BCCA-R03-1083
Study First Received: December 13, 2007
Last Updated: March 7, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Lung Neoplasms
Tobacco Use Disorder
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Substance-Related Disorders
Mental Disorders
Epigallocatechin gallate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Neuroprotective Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014