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

Stage I Prostate Cancer Clinical Trial

Official title:

Phase II, Randomized, Double Blind, Placebo Controlled Pilot Study of Polyphenon E in Men With Localized Prostate Cancer Scheduled to Undergo Radical Prostatectomy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01340599
• Other study ID #: CASE13805
• Secondary ID: NCI-2011-00606
• Status: Terminated
• Phase: Phase 2
• First received: April 20, 2011
• Last updated: March 14, 2012
• Start date: October 2006
• Est. completion date: April 2007

Study information

• Verified date: March 2012
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: April 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 45 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Stage I Prostate Cancer
• Stage IIA Prostate Cancer
• Stage IIB Prostate Cancer

Intervention

Dietary Supplement:
• defined green tea catechin extract
Given PO

Other:
• placebo
Given PO
• immunohistochemistry staining method
Correlative studies
• immunoenzyme technique
Correlative studies
• questionnaire administration
Ancillary studies

Procedure:
• therapeutic conventional surgery
Undergo radical prostatectomy

Other:
• high performance liquid chromatography
Correlative studies
• mass spectrometry
Correlative studies

Locations

Country	Name	City	State
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Changes in the levels of free (f) PSA	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.	After 0, 4, and 6 weeks	No
Secondary	Catechin levels	Extraction of Catechins from Prostate Tissue, plasma and urine samples	At baseline, 4 weeks after supplementation, and at time of surgery	No
Secondary	Number of pts with adverse events as a measure of safety and tolerability	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.	At baseline and every 4 weeks	Yes
Secondary	Changes in the levels of total (t) PSA	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.	After 0, 4, and 6 weeks	No