Green Tea Extract in Treating Patients With Nonmetastatic Bladder Cancer

Stage III Bladder Cancer Clinical Trial

Official title:

A Phase II Randomized, Placebo-Controlled Trial of Polyphenon E to Evaluate Bladder Tissue Levels of EGCG

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00666562
• Other study ID #: NCI-2009-00906
• Secondary ID: NCI-2009-00906CO
• Status: Completed
• Phase: Phase 2
• First received: April 24, 2008
• Last updated: October 17, 2017
• Start date: July 2, 2008
• Est. completion date: June 9, 2017

Study information

• Verified date: October 2017
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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., 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 9, 2017
• Est. primary completion date: April 26, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Stage I Bladder Cancer
• Stage II Bladder Cancer
• Stage III Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Dietary Supplement:
• Defined Green Tea Catechin Extract
Given orally

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Drug:
• Placebo
Given orally

Procedure:
• Therapeutic Conventional Surgery
Undergo surgery

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Minneapolis Veterans Medical Center	Minneapolis	Minnesota
United States	University of Rochester	Rochester	New York
United States	Urology San Antonio Research PA	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Comparison of nonmalignant bladder tissue levels of EGCG between the placebo group and the EGCG groups combined using student t-test.	up to 28 days
Secondary	Levels of EGCG in Malignant Bladder Tissue		up to 28 days
Secondary	Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry		up to 28 days
Secondary	Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA		Baseline and up to day 28
Secondary	Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples		up to 28 days
Secondary	Absolute Change for Baseline From EGCG in Serum Samples	The difference between the amount at the end of study (up to 28 days) from baseline.	Baseline and up to 28 days
Secondary	Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT)		At Baseline
Secondary	Serum IGFBP-3 Levels Assessed by ELISA		Baseline and up to 28 days
Secondary	Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples		up to 28 days
Secondary	Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples	The difference between the amount at the end of study (up to 28 days) from baseline.	Baseline and up to 28 days
Secondary	Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples	The difference between the amount at the end of study (up to 28 days) from baseline.	Baseline and up to 28 days
Secondary	Absolute Change for Baseline of EGCG in Urine Samples	The difference between the amount at the end of study (up to 28 days) from baseline.	Baseline and up to 28 days
Secondary	Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT)		At Baseline