NCT00666562

Green Tea Extract in Treating Patients With Nonmetastatic Bladder Cancer

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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., 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

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

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Defined Green Tea Catechin Extract	Given orally
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Placebo	Given orally
PROCEDURE	Therapeutic Conventional Surgery	Undergo surgery

Timeline

• Start date: 2008-07-02
• Primary completion: 2012-04-26
• Completion: 2017-06-09
• First posted: 2008-04-25
• Last updated: 2017-11-17
• Results posted: 2016-03-28

Locations

6 sites across 1 country: United States