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

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ClinicalTrials.gov Identifier: NCT00573885
Recruitment Status : Completed
First Posted : December 14, 2007
Last Update Posted : March 9, 2012
Sponsor:
Collaborators:
National Cancer Institute (NCI)
University of Cincinnati
Information provided by (Responsible Party):
British Columbia Cancer Agency

Tracking Information
First Submitted Date  ICMJE December 13, 2007
First Posted Date  ICMJE December 14, 2007
Last Update Posted Date March 9, 2012
Study Start Date  ICMJE January 2008
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2012)
  • Changes in oncogene/tumor suppression gene expression (part 1; completed March 22, 2006) [ Time Frame: 36 months ]
  • Phase I and II enzyme regulation by Affymetrix chip analysis in bronchial brush cells (part 1) [ Time Frame: 60 months ]
  • C-reactive protein level in plasma before treatment and 1 and 2 months after treatment (part 1) [ Time Frame: 60 months ]
  • Quantitative sputum score by image analysis before and 6 months after treatment (part 2) [ Time Frame: 36 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 13, 2007)
  • Changes in oncogene/tumor suppression gene expression (part 1; completed March 22, 2006)
  • Phase I & II enzymes regulation by Affymetrix chip analysis in bronchial brush cells (part 1)
  • C-reactive protein level in plasma before treatment and 1 and 2 months after treatment (part 1)
  • Quantitative sputum score by image analysis before and 6 months after treatment (part 2)
Change History Complete list of historical versions of study NCT00573885 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2012)
  • Change in pathology grade of bronchial biopsies (part 2) [ Time Frame: 36 months ]
  • Morphometric index of bronchial biopsies and bronchoalveolar lavage cells (BAL) (part 2) [ Time Frame: 36 months ]
  • Methylation markers in sputa and BAL cells (part 2) [ Time Frame: 60 months ]
  • Ki-67 expression (part 2) [ Time Frame: 60 months ]
  • Cleaved caspase 3, p53, and VEGF assays in bronchial biopsies (part 2) [ Time Frame: 60 months ]
  • Oncogene and tumor suppression gene expression (part 2) [ Time Frame: 60 months ]
  • Phase I and II enzyme regulation by Affymetrix chip analysis of RNA from bronchial brush cells (part 2) [ Time Frame: 60 months ]
  • C-reactive protein levels in plasma before treatment, and 6 months after treatment (part 2) [ Time Frame: 36 months ]
  • Resolution or progression of non-calcified lung nodules on spiral CT (part 2) [ Time Frame: 60 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2007)
  • Change in pathology grade of bronchial biopsies (part 2)
  • Morphometric index of bronchial biopsies and bronchoalveolar lavage cells (BAL) (part 2)
  • Methylation markers in sputa and BAL cells (part 2)
  • Ki-67 expression (part 2)
  • Cleaved caspase 3, p53, and VEGF assays in bronchial biopsies (part 2)
  • Oncogene and tumor suppression gene expression (part 2)
  • Phase I & II enzymes regulation by Affymetrix chip analysis of RNA from bronchial brush cells (part 2)
  • C-reactive protein levels in plasma before treatment, and 6 months after treatment (part 2)
  • Resolution or progression of non-calcified lung nodules on spiral CT (part 2)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Green Tea Extract in Preventing Cancer in Former and Current Heavy Smokers With Abnormal Sputum
Official Title  ICMJE Phase II Trial of Polyphenon E in Former Smokers With Abnormal Sputa
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Lung Cancer
  • Tobacco Use Disorder
Intervention  ICMJE
  • Drug: defined green tea catechin extract
    Given orally
  • Other: placebo
    Given orally
Study Arms  ICMJE
  • Experimental: Arm I
    Patients receive oral defined green tea catechin extract twice daily for 6 months.
    Intervention: Drug: defined green tea catechin extract
  • Placebo Comparator: Arm II
    Patients receive oral placebo twice daily for 6 months.
    Intervention: Other: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 7, 2012)
53
Original Enrollment  ICMJE
 (submitted: December 13, 2007)
120
Actual Study Completion Date  ICMJE December 2008
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years to 74 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00573885
Other Study ID Numbers  ICMJE CDR0000578191
P01CA096964 ( U.S. NIH Grant/Contract )
BCCA-H03-61083
BCCA-R03-1083
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party British Columbia Cancer Agency
Study Sponsor  ICMJE British Columbia Cancer Agency
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • University of Cincinnati
Investigators  ICMJE
Study Chair: Stephen Lam, MD British Columbia Cancer Agency
PRS Account British Columbia Cancer Agency
Verification Date March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP