Lung CancerPhase 2NCT00611650
Green Tea Extract in Treating Current or Former Smokers With Bronchial Dysplasia
A Phase 2 study testing defined green tea catechin extract in people with Lung Cancer and Precancerous Condition, run by British Columbia Cancer Agency at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 45 to 74 years
- Conditions the study is for
- Lung Cancer, Precancerous Condition, Tobacco Use Disorder
- What is being tested?
- defined green tea catechin extract
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2006to Jul 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
Canada1 site
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia
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.
Read the 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.
- Conditions
- Lung Cancer, Precancerous Condition, Tobacco Use Disorder
- Being tested
- defined green tea catechin extract, placebo
- Keywords
- non-small cell lung cancer, squamous lung dysplasia, tobacco use disorder
- Medical subject headings
- Lung Neoplasms, Precancerous Conditions, Tobacco Use Disorder, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
defined green tea catechin extractDrug
Given orally
placeboOther
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive oral Polyphenon E twice daily for 3 months in the absence of disease progression or unacceptable toxicity. Receives: Drug: defined green tea catechin extract |
| Arm II | Placebo comparator | Patients receive a placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the severity of dysplasia (as defined by WHO criteria) in bronchial biopsy specimens as assessed at baseline and at 3 months
Measured: 3 months
Secondary outcomes (8)
Change in the morphometric index in bronchial biopsy specimens as assessed at baseline and at 3 months
Measured: 3 months
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
Measured: 3 months
Methylation biomarkers in bronchoalveolar lavage (BAL) cells as assessed at baseline and at 3 months
Measured: 3 months
Oncogene/ tumor suppressor gene expression in bronchial brush cells as assessed by cDNA microarray analysis at baseline and at 3 months
Measured: 3 months
Phase I and II enzyme regulation in bronchial brush cells as assessed by Affymetrix microarray analysis at baseline and at 3 months
Measured: 3 months
Change in C-reactive protein levels in plasma as assessed by enzyme-linked immunoassay (ELISA) at baseline and then monthly for 3 months
Measured: 3 months
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
Measured: 24 months
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
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2008 (estimated)
- Study startOct 2006
- Primary completionJun 2011
- Study completionJul 2011
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- British Columbia Cancer Agency
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), University of Cincinnati
- Responsible party
- Sponsor
- Investigators
- Stephen Lam, MD, Study chair, British Columbia Cancer Agency
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00611650
- Sponsor's protocol ID
- CDR0000578224
- Other IDs
- P01CA096964, BCCA-H07-02401, H07-02401
- Status last verified
- Mar 2012
- First submitted
- 8 Feb 2008
- Last updated
- 9 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia
- ClinicalTrials.gov ID
- NCT00611650
- Acronym / sponsor ID
- CDR0000578224
- Conditions
- Lung Cancer, Precancerous Condition, Tobacco Use Disorder
- Keywords
- non-small cell lung cancer, squamous lung dysplasia, tobacco use disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 23 participants (actual)
- Lead sponsor
- British Columbia Cancer AgencyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), University of Cincinnati
- Study start
- Oct 2006
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: defined green tea catechin extractPatients receive oral Polyphenon E twice daily for 3 months in the absence of disease progression or unacceptable toxicity. |
| Arm II | Placebo comparator | Other: placeboPatients receive a placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 45 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| defined green tea catechin extractGiven orally | Drug | Arm I |
| placeboGiven orally | Other | Arm II |
Primary outcome
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
8 secondary outcomes
Change in the morphometric index in bronchial biopsy specimens as assessed at baseline and at 3 months
Time frame: 3 months
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
Methylation biomarkers in bronchoalveolar lavage (BAL) cells as assessed at baseline and at 3 months
Time frame: 3 months
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
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
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
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
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
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2012.
Related trials for Lung Cancer
RecruitingObservational study
Dual Energy CT - a Tool for Delineation of Tumor and Organs at Risk in Radiotherapy
Brain Metastases, Bone Metastases
Active, not recruitingPhase 3
A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions
Carcinoma, Non-Small-Cell Lung
RecruitingObservational study
Genetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer
Kidney Neoplasms, Kidney Cancer
RecruitingPhase 1
Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease
Recurrent Small Cell Lung Cancer, Extensive-Stage Small Cell Lung Cancer
Enrolling by invitationObservational study
Patient Reported Outcomes Following Percutaneous Lung Ablation
Lung Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Lam, MD study chair
British Columbia Cancer Agency
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing defined green tea catechin extract in people with Lung Cancer and Precancerous Condition, run by British Columbia Cancer Agency at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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 (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2012.