Green Tea Extract in Treating Patients With Nonmetastatic Bladder Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00666562
• Collaborator: (none)
• Enrollment: 31
• Locations: 6
• Arms: 3
• Actual Duration (Months): 107.2
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Stage I Bladder Cancer; Stage II Bladder Cancer; Stage III Bladder Cancer	Dietary Supplement: Defined Green Tea Catechin Extract; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Placebo; Procedure: Therapeutic Conventional Surgery	Phase 2

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:

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

2. 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

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

2. 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.

3. 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.

4. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase II Randomized, Placebo-Controlled Trial of Polyphenon E to Evaluate Bladder Tissue Levels of EGCG
• Actual Study Start Date: Jul 2, 2008
• Actual Primary Completion Date: Apr 26, 2012
• Actual Study Completion Date: Jun 9, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Arm I (placebo) Patients receive six oral placebo capsules once daily for 14-28 days.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Placebo; Given orally; Other Names: placebo therapy PLCB sham therapy
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 Names: Polyphenon E Polyphenon E TM ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Placebo; Given orally; Other Names: placebo therapy PLCB sham therapy
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 Names: Polyphenon E Polyphenon E TM ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Procedure: Therapeutic Conventional Surgery; Undergo surgery

Outcome Measures

Primary Outcome Measures

1. Epigallocatechin Gallate (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) [up to 28 days]

   Comparison of nonmalignant bladder tissue levels of EGCG between the placebo group and the EGCG groups combined using student t-test.

Secondary Outcome Measures

1. Levels of EGCG in Malignant Bladder Tissue [up to 28 days]

2. Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry [up to 28 days]

3. Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA [Baseline and up to day 28]

4. Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples [up to 28 days]

5. Absolute Change for Baseline From EGCG in Serum Samples [Baseline and up to 28 days]

   The difference between the amount at the end of study (up to 28 days) from baseline.

6. Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) [At Baseline]

7. Serum IGFBP-3 Levels Assessed by ELISA [Baseline and up to 28 days]

8. Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples [up to 28 days]

9. Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples [Baseline and up to 28 days]

   The difference between the amount at the end of study (up to 28 days) from baseline.

10. Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples [Baseline and up to 28 days]

    The difference between the amount at the end of study (up to 28 days) from baseline.

11. Absolute Change for Baseline of EGCG in Urine Samples [Baseline and up to 28 days]

    The difference between the amount at the end of study (up to 28 days) from baseline.

12. Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) [At Baseline]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
3	Minneapolis Veterans Medical Center	Minneapolis	Minnesota	United States	55417
4	University of Rochester	Rochester	New York	United States	14642
5	Urology San Antonio Research PA	San Antonio	Texas	United States	78229
6	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Tracy Downs, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00666562
• Other Study ID Numbers: NCI-2009-00906; NCI-2009-00906; CO06810; CDR0000594276; H-2007-0250; UWI06-8-01; UWI06-8-01; N01CN35153; P30CA014520
• First Posted: Apr 25, 2008
• Last Update Posted: Nov 17, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Epigallocatechin gallate

Study Results

Participant Flow

Recruitment Details	Participants were recruited during a 4 year period by staff at 5 participating institutions (both University hospitals and community clinics).

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	11	10	10
COMPLETED	11	8	10
NOT COMPLETED	0	2	0

Baseline Characteristics

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)	Total
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	11	10	10	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 27.3%	7 70%	3 30%	13 41.9%
>=65 years	8 72.7%	3 30%	7 70%	18 58.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.00 (7.04)	65.20 (9.50)	66.20 (9.55)	67.23 (8.69)
Sex: Female, Male (Count of Participants)
Female	2 18.2%	1 10%	2 20%	5 16.1%
Male	9 81.8%	9 90%	8 80%	26 83.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 27.3%	2 20%	2 20%	7 22.6%
Not Hispanic or Latino	8 72.7%	8 80%	8 80%	24 77.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 10%	1 3.2%
White	11 100%	10 100%	9 90%	30 96.8%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%	10 100%	10 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Epigallocatechin Gallate (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)
Description	Comparison of nonmalignant bladder tissue levels of EGCG between the placebo group and the EGCG groups combined using student t-test.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	9	8	8
Mean (Standard Error) [ng/mL]	0.00 (0.00)	0.50 (1.42)	1.72 (3.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Placebo), Arm II (800mg Polyphenon E, Placebo), Arm III (1200mg Polyphenon E)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Levels of EGCG in Malignant Bladder Tissue
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 1 participant in Arm I, 1 participant in Arm II, and 3 participants in Arm III.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	10	7	7
Mean (Standard Deviation) [ng/mL]	0.00 (0.00)	0.00 (0.00)	2.54 (2.92)

3. Secondary Outcome

Title	Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	11	8	10
PCNA	0.41 (0.052)	0.38 (0.061)	0.35 (0.052)
MMP2	0.16 (0.026)	0.18 (0.054)	0.16 (0.069)
Clusterin	0.074 (0.032)	0.061 (0.020)	0.046 (0.013)
VEGF	0.011 (0.0065)	0.021 (0.0173)	0.013 (0.0066)
p27	0.36 (0.080)	0.35 (0.090)	0.31 (0.057)

4. Secondary Outcome

Title	Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA
Time Frame	Baseline and up to day 28

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 2 participants in Arm I.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	9	8	10
Baseline	135.06 (22.64)	122.22 (37.49)	132.12 (15.12)
End of Study	131.86 (15.59)	124.22 (38.06)	132.27 (27.77)

5. Secondary Outcome

Title	Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 1 participant in Arm I, 1 participant in Arm II, and 3 participants in Arm III.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	10	7	7
epicatechin gallate (ECG)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
epicatechin (EC)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
epigallocatechin (EGC)	0.00 (0.00)	0.00 (0.00)	0.60 (1.58)

6. Secondary Outcome

Title	Absolute Change for Baseline From EGCG in Serum Samples
Description	The difference between the amount at the end of study (up to 28 days) from baseline.
Time Frame	Baseline and up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 2 participants in Arm I and 1 participant in Arm II.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	9	7	10
Mean (Standard Deviation) [ng/mL]	0.28 (1.11)	82.33 (83.66)	85.37 (76.34)

7. Secondary Outcome

Title	Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT)
Time Frame	At Baseline

Outcome Measure Data

Analysis Population Description

This outcome was assessed in all participants,combined irrespective of their randomization. Analysis was not able to be completed on 4 participants.

Arm/Group Title	Glycine/Glycine	Alanine/Glycine	Alanine/Alanine
Arm/Group Description	G to G transition in the COMT gene	A to G transition in the COMT gene	A to A transition in the COMT gene
Measure Participants	6	11	8
Plasma	4.12 (4.80)	0.57 (1.89)	2.48 (3.48)
Serum	0.00 (0.00)	0.69 (1.82)	0.43 (1.21)

8. Secondary Outcome

Title	Serum IGFBP-3 Levels Assessed by ELISA
Time Frame	Baseline and up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 2 participants in Arm I.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	9	8	10
Baseline	1918.31 (607.16)	1679.61 (556.59)	1824.86 (559.58)
End of Study	2020.31 (701.46)	1800.08 (490.92)	1624.03 (611.89)

9. Secondary Outcome

Title	Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 2 participants in Arm I and 2 participants in Arm III.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	9	8	8
epicatechin gallate (ECG)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
epicatechin (EC)	0.00 (0.00)	0.00 (0.00)	0.20 (0.55)
epigallocatechin (EGC)	0.00 (0.00)	0.20 (0.55)	0.00 (0.00)

10. Secondary Outcome

Title	Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples
Description	The difference between the amount at the end of study (up to 28 days) from baseline.
Time Frame	Baseline and up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 3 participants in Arm I and 1 participant in Arm II.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	8	7	10
epicatechin gallate (ECG)	0.00 (0.00)	1.13 (1.78)	1.49 (2.13)
epicatechin (EC)	0.52 (1.46)	2.41 (3.15)	5.33 (6.78)
Epigallocatechin (EGC)	0.20 (0.55)	3.60 (3.21)	12.16 (11.09)

11. Secondary Outcome

Title	Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples
Description	The difference between the amount at the end of study (up to 28 days) from baseline.
Time Frame	Baseline and up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 2 participants in Arm I and 1 participant in Arm II.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	9	7	10
epicatechin gallate (ECG)	0.17 (0.52)	8.38 (11.03)	8.62 (9.14)
epicatechin (EC)	0.00 (0.00)	0.97 (1.97)	0.31 (0.66)
epigallocatechin (EGC)	0.00 (0.00)	6.93 (10.06)	3.46 (4.04)

12. Secondary Outcome

Title	Absolute Change for Baseline of EGCG in Urine Samples
Description	The difference between the amount at the end of study (up to 28 days) from baseline.
Time Frame	Baseline and up to 28 days

Outcome Measure Data

Analysis Population Description

Analysis was not able to be completed for 3 participants in Arm I and 1 participant in Arm II.

Arm/Group Title	Arm I (Placebo)	Arm II (800mg Polyphenon E, Placebo)	Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies	Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Measure Participants	8	7	10
Mean (Standard Deviation) [ng/mL]	0.00 (0.00)	1.93 (0.98)	3.38 (1.60)

13. Secondary Outcome

Title	Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT)
Time Frame	At Baseline

Outcome Measure Data

Analysis Population Description

This outcome was assessed in all participants,combined irrespective of their randomization. Analysis was not able to be completed for 4 participants.

Arm/Group Title	5/6 Genotype	6/6 Genotype	6/7 Genotype	7/7 Genotype
Arm/Group Description	Genotype of the UGT in EGCG	Genotype of the UGT in EGCG	Genotype of the UGT in EGCG	Genotype of the UGT in EGCG
Measure Participants	2	7	15	1
Plasma	2.97 (4.20)	2.09 (3.75)	2.02 (3.58)	0.00 (0.00)
Urine	1.72 (2.43)	0.86 (2.27)	0.10 (0.40)	0.00 (0.00)

Adverse Events

Arm/Group Title	Arm I (Placebo)		Arm II (800mg Polyphenon E, Placebo)		Arm III (1200mg Polyphenon E)
Arm/Group Description	Patients receive six oral placebo capsules once daily for 14-28 days. After completion of study treatment, patients undergo trans-urethral resection of bladder tumor or cystectomy. placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies		Patients receive four oral 800mg polyphenon E capsules and two oral placebo 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. defined green tea catechin extract: Given orally placebo: Given orally pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies		Patients receive six oral 1200mg 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. defined green tea catechin extract: Given orally therapeutic conventional surgery: Undergo surgery pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Arm I (Placebo)		Arm II (800mg Polyphenon E, Placebo)		Arm III (1200mg Polyphenon E)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Placebo)		Arm II (800mg Polyphenon E, Placebo)		Arm III (1200mg Polyphenon E)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Placebo)		Arm II (800mg Polyphenon E, Placebo)		Arm III (1200mg Polyphenon E)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		5/10 (50%)		6/10 (60%)
Cardiac disorders
Sinus bradycardia	1/11 (9.1%)	1	0/10 (0%)	0	0/10 (0%)	0
Hypertension	0/11 (0%)	0	1/10 (10%)	1	1/10 (10%)	1
Ear and labyrinth disorders
Tinnitus	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Eye disorders
photophobia	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Gastrointestinal disorders
Flatulence	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
heartburn	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Nausa	0/11 (0%)	0	0/10 (0%)	0	2/10 (20%)	2
taste alteration	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
abdominal pain	0/11 (0%)	0	1/10 (10%)	4	1/10 (10%)	1
anal pain	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
General disorders
Fatigue	0/11 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
headache	0/11 (0%)	0	1/10 (10%)	1	4/10 (40%)	4
Immune system disorders
imb	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Infections and infestations
Urinary Tract infection	1/11 (9.1%)	1	0/10 (0%)	0	0/10 (0%)	0
Metabolism and nutrition disorders
hyperglycemia	1/11 (9.1%)	1	0/10 (0%)	0	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
back pain	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
extremity limb pain	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
joint pain	0/11 (0%)	0	1/10 (10%)	2	1/10 (10%)	3
muscle pain	0/11 (0%)	0	0/10 (0%)	0	2/10 (20%)	2
pelvis pain	0/11 (0%)	0	1/10 (10%)	2	0/10 (0%)	0
Psychiatric disorders
Anxiety	0/11 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Renal and urinary disorders
kidney pain	0/11 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Flushing	0/11 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
pruritus	0/11 (0%)	0	1/10 (10%)	1	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.