Green Tea Extract in Treating Patients With Nonmetastatic Bladder Cancer

NCT ID: NCT00666562

Last Updated: 2017-11-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-02

Study Completion Date

2017-06-09

Brief Summary

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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.

Detailed Description

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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., Proliferating Cell Nuclear Antigen \[PCNA\], Matrix Metallopeptidase 2 \[MMP2\], clusterin, Vascular endothelial Growth Factor \[VEGF\], 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 Catechol-O-Methyltransferase (COMT) and Uridinediphosphate-Glucuronosyltransferase (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 Insulin Growth Factor 1 (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.

Conditions

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Stage I Bladder Cancer Stage II Bladder Cancer Stage III Bladder Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm I (placebo)

Patients receive six oral placebo capsules once daily for 14-28 days.

Group Type PLACEBO_COMPARATOR

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Placebo

Intervention Type DRUG

Given orally

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.

Group Type EXPERIMENTAL

Defined Green Tea Catechin Extract

Intervention Type DIETARY_SUPPLEMENT

Given orally

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Placebo

Intervention Type DRUG

Given orally

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.

Group Type EXPERIMENTAL

Defined Green Tea Catechin Extract

Intervention Type DIETARY_SUPPLEMENT

Given orally

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Interventions

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Defined Green Tea Catechin Extract

Given orally

Intervention Type DIETARY_SUPPLEMENT

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Placebo

Given orally

Intervention Type DRUG

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Other Intervention Names

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Polyphenon E Polyphenon E TM placebo therapy PLCB sham therapy

Eligibility Criteria

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Inclusion Criteria

* 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
* White Blood Cell (WBC) \>= 3,000/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 10 g/dL
* Alkaline phosphatase =\< upper limit of normal (ULN)
* Bilirubin =\< ULN
* Asparate Aminotransferase (AST) and Alanine Transaminase (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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tracy Downs

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status

Minneapolis Veterans Medical Center

Minneapolis, Minnesota, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Urology San Antonio Research PA

San Antonio, Texas, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2009-00906

Identifier Type: REGISTRY

Identifier Source: secondary_id

CO06810

Identifier Type: -

Identifier Source: secondary_id

CDR0000594276

Identifier Type: -

Identifier Source: secondary_id

H-2007-0250

Identifier Type: -

Identifier Source: secondary_id

UWI06-8-01

Identifier Type: OTHER

Identifier Source: secondary_id

UWI06-8-01

Identifier Type: OTHER

Identifier Source: secondary_id

N01CN35153

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014520

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00906

Identifier Type: -

Identifier Source: org_study_id