Defined Green Tea Catechin Extract in Treating Patients With Localized Prostate Cancer Undergoing Surgery

Phase 2

Terminated

• Conditions: Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer
• Interventions: Dietary Supplement: defined green tea catechin extract; Other: placebo; Other: immunohistochemistry staining method; Other: immunoenzyme technique; Other: questionnaire administration; Procedure: therapeutic conventional surgery; Other: high performance liquid chromatography; Other: mass spectrometry

• Registration Number: NCT01340599
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

This randomized pilot phase II trial studies the side effects and how well defined green tea catechin extract works in treating patients with localized prostate cancer undergoing surgery. Defined green tea catechin extract contains ingredients that may prevent or slow the growth of certain cancers.

Detailed Description

OBJECTIVES:

I. To evaluate the short-term effects of daily Polyphenon E (defined green tea catechin extract) administration (800 mg epigallocatechin-3-gallate \[EGCG\] once daily \[QD\]) during the interval between prostate biopsy and radical prostatectomy (approximately 6 weeks) in men with localized prostate cancer.

II. Compare the change in levels of intermediate biomarkers (Ki-67, B-cell lymphoma 2 \[Bcl2\], cyclin D, KiP1/P27, vascular endothelial growth factor \[VEGF\], and cluster of differentiation \[CD\]31) in biopsy (pre-treatment) and prostatectomy (post-treatment) specimens collected from subjects treated with Polyphenon E or placebo during the period between biopsy and prostatectomy.

III. Compare the change in pre- and post-treatment serum prostate-specific antigen (PSA) level in subjects treated with Polyphenon E or placebo during the period between biopsy and prostatectomy.

IV. Evaluate bioavailability of catechins from Polyphenon E (plasma and tissue catechin levels, catechin metabolites in urine).

V. Evaluate the safety and tolerability of Polyphenon E in this subject population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive defined green tea catechin extract orally (PO) QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.

ARM II: Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.

After completion of study treatment, patients are followed up periodically.

Study Timeline

• Study Start: 2006-10
• Primary Completion: 2007-04
• Study Completion: 2007-04
• Study First Submitted: 2011-04-20
• Study First Submitted QC: 2011-04-21
• Study First Posted: 2011-04-22
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-14
• Last Update Posted: 2012-03-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 5

Inclusion Criteria

• Prostate biopsy positive for cancer; clinically localized T1 and T2 stage disease expected, with biopsy specimen available for baseline biomarker measurements
• Scheduled for a radical prostatectomy
• Willing to sign an Institutional Review Board (IRB)-approved informed consent document and adhere to the protocol
• Willing and able to take oral medications
• Willing to refrain from drinking any kind of tea (including herbal tea) or using supplements containing green tea constituents for the duration of the study

Exclusion Criteria

• Prior hormonal or surgical therapy for prostate cancer; including prior brachytherapy or radiation therapy
• Recent consumption of tea (six or more cups per day) or use of supplements containing green tea within one week of randomization
• Signs or symptoms of progressive or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic or cerebral disease
• Serum creatinine >= 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) >= ULN
• Aspartate aminotransferase (AST) >= ULN
• Alkaline phosphatase (ALP) >= ULN
• Albumin (ALB) =< lower limit of normal (LLN)
• Total bilirubin >= ULN
• Known malignancy at any site within the last five years; with the exception of basal cell carcinoma (BCC)
• Participation in a research trial within the past three months
• Any condition that would interfere with the ability to give informed consent or comply with the study protocol
• Hypersensitivity to tea products or any of the inactive ingredients found in the drug product capsules
• Concomitant use of at least 400 mg per day of a nonsteroidal anti-inflammatory (NSAID) agent two or more times per week

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (Polyphenon E)	defined green tea catechin extract	Patients receive defined green tea catechin extract PO once daily QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm I (Polyphenon E)	immunohistochemistry staining method	Patients receive defined green tea catechin extract PO once daily QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm I (Polyphenon E)	immunoenzyme technique	Patients receive defined green tea catechin extract PO once daily QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm I (Polyphenon E)	questionnaire administration	Patients receive defined green tea catechin extract PO once daily QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm I (Polyphenon E)	therapeutic conventional surgery	Patients receive defined green tea catechin extract PO once daily QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm I (Polyphenon E)	high performance liquid chromatography	Patients receive defined green tea catechin extract PO once daily QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm I (Polyphenon E)	mass spectrometry	Patients receive defined green tea catechin extract PO once daily QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm II (placebo)	placebo	Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm II (placebo)	immunohistochemistry staining method	Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm II (placebo)	immunoenzyme technique	Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm II (placebo)	questionnaire administration	Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm II (placebo)	therapeutic conventional surgery	Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm II (placebo)	high performance liquid chromatography	Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.
Arm II (placebo)	mass spectrometry	Patients receive placebo PO QD for 4-10 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo radical prostatectomy between days 28-70.

Primary Outcome Measures

Name	Time	Method
Change in levels of intermediate biomarkers in prostate tissue (Ki-67, Bcl2, cyclin D, KiP1/P27, VEGF, and CD31) during treatment with defined green tea catechin extract or placebo during the period between biopsy and prostatectomy	Baseline and at or after 6 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Changes in the levels of free (f) PSA	After 0, 4, and 6 weeks	PSA exists in the serum in different molecular forms and that the proportion of "complexed" PSA (PSA-ACT) to "free" PSA(F-PSA) is higher in prostate cancer patients \[16\]. F-PSA-to-PSA ratio remains constant in men without prostate cancer while total PSA increases. This F-PSA to-PSA ratio is useful diagnostic tool with borderline total PSA values (4.0 to 10.0 ng/mL); additionally values of 20% to 25% F-PSA eliminates 1/3 of biopsies in some studies; and F-PSA of 15.6% and PSA-ACT of 26.7% yielded 95% sensitivity \[17\]. The F-PSA-to-PSA ratio does not correlate to grade or stage of cancer.
Catechin levels	At baseline, 4 weeks after supplementation, and at time of surgery	Extraction of Catechins from Prostate Tissue, plasma and urine samples
Number of pts with adverse events as a measure of safety and tolerability	At baseline and every 4 weeks	AEs will be recorded from the date the informed consent document is signed until the day of surgery. Liver function tests including the Hepatic Function Panel \[Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Aminotransferace (AST), total and direct Bilirubin\], as well as amylase and lipase tests will be monitored at baseline and every four (4) weeks for the duration of the study.
Changes in the levels of total (t) PSA	After 0, 4, and 6 weeks	PSA exists in the serum in different molecular forms and that the proportion of "complexed" PSA (PSA-ACT) to "free" PSA(F-PSA) is higher in prostate cancer patients \[16\]. F-PSA-to-PSA ratio remains constant in men without prostate cancer while total PSA increases. This F-PSA to-PSA ratio is useful diagnostic tool with borderline total PSA values (4.0 to 10.0 ng/mL); additionally values of 20% to 25% F-PSA eliminates 1/3 of biopsies in some studies; and F-PSA of 15.6% and PSA-ACT of 26.7% yielded 95% sensitivity \[17\]. The F-PSA-to-PSA ratio does not correlate to grade or stage of cancer.

Trial Locations

Locations (1)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States