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

Phase II Trial of Polyphenon E in Former Smokers With Abnormal Sputa

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.

Study Overview

• Status: Completed
• Conditions: Tobacco Use Disorder; Lung Cancer
• Intervention / Treatment: Other: placebo; Drug: defined green tea catechin extract

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: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm II; Patients receive oral placebo twice daily for 6 months.	Other: placebo; Given orally
Experimental: Arm I; Patients receive oral defined green tea catechin extract twice daily for 6 months.	Drug: defined green tea catechin extract; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in oncogene/tumor suppression gene expression (part 1; completed March 22, 2006)	36 months
Phase I and II enzyme regulation by Affymetrix chip analysis in bronchial brush cells (part 1)	60 months
C-reactive protein level in plasma before treatment and 1 and 2 months after treatment (part 1)	60 months
Quantitative sputum score by image analysis before and 6 months after treatment (part 2)	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in pathology grade of bronchial biopsies (part 2)	36 months
Morphometric index of bronchial biopsies and bronchoalveolar lavage cells (BAL) (part 2)	36 months
Methylation markers in sputa and BAL cells (part 2)	60 months
Ki-67 expression (part 2)	60 months
Cleaved caspase 3, p53, and VEGF assays in bronchial biopsies (part 2)	60 months
Oncogene and tumor suppression gene expression (part 2)	60 months
Phase I and II enzyme regulation by Affymetrix chip analysis of RNA from bronchial brush cells (part 2)	60 months
C-reactive protein levels in plasma before treatment, and 6 months after treatment (part 2)	36 months
Resolution or progression of non-calcified lung nodules on spiral CT (part 2)	60 months

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Collaborators: National Cancer Institute (NCI); University of Cincinnati

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: December 13, 2007
• First Submitted That Met QC Criteria: December 13, 2007
• First Posted (Estimate): December 14, 2007

Study Record Updates

• Last Update Posted (Estimate): March 9, 2012
• Last Update Submitted That Met QC Criteria: March 7, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; small cell lung cancer; tobacco use disorder
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Tobacco Use Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Epigallocatechin gallate
• Other Study ID Numbers: CDR0000578191; P01CA096964 (U.S. NIH Grant/Contract); BCCA-H03-61083; BCCA-R03-1083