Green Tea Extract in Treating Patients With Nonmetastatic Bladder Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00666562
First received: April 24, 2008
Last updated: May 31, 2013
Last verified: May 2013
  Purpose

Green tea extract contains ingredients that may slow the growth of certain cancers. It is not yet known whether green tea extract is more effective than a placebo when given before surgery in treating patients with bladder. This randomized phase II trial is studying green tea extract to see how well it works compared to a placebo when given before surgery in treating patients with nonmetastatic bladder cancer.


Condition Intervention Phase
Stage I Bladder Cancer
Stage II Bladder Cancer
Stage III Bladder Cancer
Dietary Supplement: defined green tea catechin extract
Drug: placebo
Procedure: therapeutic conventional surgery
Other: pharmacological study
Other: laboratory biomarker analysis
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: A Phase II Randomized, Placebo-Controlled Trial of Polyphenon E to Evaluate Bladder Tissue Levels of EGCG

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • EGCG levels in nonmalignant bladder tissue (e.g., normal-appearing urothelium, inflammatory lesions in the bladder, sessile noninvasive bladder tumors, and papillary noninvasive bladder tumors) [ Time Frame: End of surgery ] [ Designated as safety issue: No ]
    Comparison of nonmalignant bladder tissue levels of EGCG between the placebo group and the EGCG groups combined using student t-test. In the case of violation of normality assumptions, an appropriate transformation of the data such as logarithm will be considered or a nonparametric test such as Wilcoxon rank-sum test will be used for comparison.


Secondary Outcome Measures:
  • Levels of EGCG in malignant bladder tissue [ Time Frame: End of surgery ] [ Designated as safety issue: No ]
  • Levels of surrogate intermediate endpoint biomarkers in malignant and nonmalignant bladder tissue assessed by immunohistochemistry [ Time Frame: End of surgery ] [ Designated as safety issue: No ]
  • Serum IGF-1 and IGFBP-3 levels assessed by ELISA [ Time Frame: Baseline and up to day 28 ] [ Designated as safety issue: No ]
  • Levels of other catechins found in polyphenon E (i.e., epicatechin, epicatechin gallate, and epigallocatechin) in serum, urine, and tissue samples [ Time Frame: Baseline and at end of surgery ] [ Designated as safety issue: No ]
  • Levels of EGCG in serum, urine, and tissue samples [ Time Frame: End of surgery ] [ Designated as safety issue: No ]
  • Metabolism of EGCG in serum, urine and tissue by COMT and UGT [ Time Frame: Baseline and at end of surgery ] [ Designated as safety issue: No ]
  • Intracellular distribution of EGCG in nonmalignant bladder tissue samples assessed by MALDI-qTOR [ Time Frame: End of surgery ] [ Designated as safety issue: No ]
  • Incidence of toxicities as assessed by NCI CTCAE v3.0 [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: July 2008
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm I (placebo)
Patients receive six oral placebo capsules once daily for 14-28 days.
Drug: placebo
Given orally
Other Name: PLCB
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (polyphenon E, placebo)
Patients receive four oral polyphenon E capsules and two oral placebo capsules once daily for 14-28 days in the absence of unacceptable toxicity.
Dietary Supplement: defined green tea catechin extract
Given orally
Other Name: Polyphenon E
Drug: placebo
Given orally
Other Name: PLCB
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (polyphenon E, trans-urethral resection or cystectomy)
Patients receive six oral polyphenon E capsules once daily for 14-28 days in the absence of unacceptable toxicity. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy.
Dietary Supplement: defined green tea catechin extract
Given orally
Other Name: Polyphenon E
Procedure: therapeutic conventional surgery
Undergo surgery
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

  Hide Detailed Description

Detailed Description:

PRIMARY OBJECTIVES I. To compare the levels of epigallocatechin-3-gallate (EGCG) in nonmalignant bladder tissue from patients with bladder cancer treated with oral polyphenon E 800 mg EGCG or polyphenon E 1200 mg EGCG once daily for 14-28 days.

SECONDARY OBJECTIVES:

I. To compare the levels of EGCG in nonmalignant versus malignant bladder tissue samples from these patients.

II. To examine the dose-response modulation of surrogate intermediate endpoint biomarkers (e.g., PCNA, MMP2, clusterin, VEGF, p27, and ODC) in malignant and nonmalignant samples of bladder tissue from these patients after administration of polyphenon E.

III. To correlate EGCG levels in samples of serum, urine, and tissue from these patients.

IV. To examine the levels of other catechins (i.e., epicatechin, epicatechin gallate, and epigallocatechin) found in polyphenon E in samples of serum, urine, and tissue from these patients.

V. To compare the metabolism of EGCG by COMT and UGT in relation to pharmacogenetic polymorphisms in COMT and UGT in samples of serum, urine, and tissue from these patients.

VI. To examine the changes in serum IGF-1 and IGFBP-3 levels after administration of polyphenon E in these patients.

OUTLINE:

This is a multicenter study. Patients are stratified according to tumor site and disease invasiveness (invasive vs noninvasive). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive six oral placebo capsules once daily for 14-28 days in the absence of unacceptable toxicity.

Arm II: Patients receive four oral polyphenon E capsules and two oral placebo capsules once daily for 14-28 days in the absence of unacceptable toxicity.

Arm III: Patients receive six oral polyphenon E capsules once daily for 14-28 days in the absence of unacceptable toxicity.

After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy.

Blood, urine, and tissue samples are obtained at baseline and at the end of study treatment for correlative laboratory studies. Samples are evaluated for pharmacokinetics of polyphenon E using high performance liquid chromatography. Levels of epigallocatechin-3-gallate [EGCG] and other catechins found in polyphenon E are assessed for correlation in serum, urine, and tissue. Intermediate endpoint biomarkers are evaluated for dose-response modulation in serum (i.e., IGF-1 and IGFBP-3) via ELISA and in bladder tissue obtained at the time of bladder surgery (i.e., PCNA, MMP2, clusterin, VEGF, p27, and ODS) via IHC. Patients at the University of Wisconsin undergo additional biopsy of bladder tissue for matrix-assisted laser desorption quadrupole time-of-flight (O-MALDI-qTOF) analysis of EGCG pharmacokinetics. Tissue samples are examined for intracellular concentration and distribution of EGCG. Genotyping studies for pyrosequencing of UGT and COMT polymorphisms are also performed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Diagnosis of bladder cancer
  • Bladder tumor discovered on cystoscopy within the past 60 days
  • Invasive or non-invasive tumor
  • Primary tumor may represent either an initial diagnosis or recurrent disease of any clinical stage
  • No metastatic disease
  • Must be an eligible candidate for a partial cystectomy, radical cystectomy, or trans-urethral resection of bladder tumor (TURBT)
  • Has not undergone any treatment for superficial or invasive bladder cancer since the diagnostic cystoscopy
  • TURBT or radical cystectomy is the planned curative surgical treatment
  • ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
  • More than 30 days since any prior intravesical therapy or adjuvant chemotherapy
  • More than 30 days since prior bladder surgery
  • Biopsies are not considered surgeries
  • No prior pelvic radiotherapy
  • No concurrent systemic chemotherapy for any other cancer, except nonmelanoma skin cancer
  • No concurrent NSAIDs (e.g., ibuprofen, naproxen, or cyclooxygenase-2 inhibitors) except =< 81 mg aspirin per day
  • Concurrent acetaminophen (Tylenol) or prescription opioids combined with acetaminophen (i.e., Percocet, Darvocet, Vicodin, Tylenol #3) allowed for pain
  • No other concurrent investigational agents
  • WBC >= 3,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 10 g/dL
  • Alkaline phosphatase =< upper limit of normal (ULN)
  • Bilirubin =< ULN
  • AST and ALT =< ULN
  • Sodium 135-144 mmol/L (inclusive)
  • Potassium 3.2-4.8 mmol/L (inclusive)
  • Chloride 85-114 mmol/L (inclusive)
  • Bicarbonate >11 mEQ/dL
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Willing to avoid green tea beverages and green tea-containing products during study participation
  • No evidence of other cancers, except nonmelanoma skin cancer
  • No history of allergic reactions attributed to tea or to any of the compounds of similar chemical or biologic composition to Polyphenon E or any of the inactive ingredients in Polyphenon E capsules
  • No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection, Symptomatic congestive heart failure, Unstable angina pectoris, Cardiac arrhythmia, Psychiatric illness/social situations that would limit study compliance
  • More than 24 hours since prior and no concurrent consumption of any other green tea supplements or more than 2 cups (16 oz) of green tea either through dietary sources or through nutritional supplementation
  • Topical cosmetics (i.e., lotions, shampoos, makeup) that contain green tea are allowed
  • Creatinine normal
  • Not pregnant or nursing
  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: NCT00666562

Locations
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Tracy Downs University of Wisconsin Hospital and Clinics
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00666562     History of Changes
Other Study ID Numbers: NCI-2009-00906, UWI06-8-01, CO06810, CDR0000594276, H-2007-0250, N01CN35153
Study First Received: April 24, 2008
Last Updated: May 31, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014