Stage I Bladder Cancer, Stage II Bladder Cancer, Stage III Bladder Cancer
Conditions
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.
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.
Interventions
DIETARY_SUPPLEMENTDefined Green Tea Catechin Extract
Given orally
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPharmacological Study
Correlative studies
DRUGPlacebo
Given orally
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Levels of EGCG in Malignant Bladder Tissue | up to 28 days | — |
| Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | up to 28 days | — |
| Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | Baseline and up to day 28 | — |
| Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | up to 28 days | — |
| 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. |
| Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | At Baseline | — |
| Serum IGFBP-3 Levels Assessed by ELISA | Baseline and up to 28 days | — |
| Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | up to 28 days | — |
| 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. |
| Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | At Baseline | — |
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited during a 4 year period by staff at 5 participating institutions (both University hospitals and community clinics).
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Placebo) 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 | 11 |
| Arm II (800mg Polyphenon E, Placebo) 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 | 10 |
| Arm III (1200mg Polyphenon E) 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 | 10 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Concomitant Medication | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm III (1200mg Polyphenon E) | Total | Arm I (Placebo) | Arm II (800mg Polyphenon E, Placebo) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 18 Participants | 8 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 13 Participants | 3 Participants | 7 Participants |
| Age, Continuous | 66.20 years STANDARD_DEVIATION 9.55 | 67.23 years STANDARD_DEVIATION 8.69 | 70.00 years STANDARD_DEVIATION 7.04 | 65.20 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 24 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 30 Participants | 11 Participants | 10 Participants |
| Region of Enrollment United States | 10 participants | 31 participants | 11 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 26 Participants | 9 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 11 | 5 / 10 | 6 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 0 / 10 |
Outcome results
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.
Time frame: up to 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Placebo) | 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) | 0.00 ng/mL | Standard Error 0 |
| Arm II (800mg Polyphenon E, Placebo) | 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) | 0.50 ng/mL | Standard Error 1.42 |
| Arm III (1200mg Polyphenon E) | 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) | 1.72 ng/mL | Standard Error 3.11 |
p-value: 0.046t-test, 2 sided
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.
Time frame: Baseline and up to 28 days
Population: Analysis was not able to be completed for 2 participants in Arm I and 1 participant in Arm II.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Placebo) | Absolute Change for Baseline From EGCG in Serum Samples | 0.28 ng/mL | Standard Deviation 1.11 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change for Baseline From EGCG in Serum Samples | 82.33 ng/mL | Standard Deviation 83.66 |
| Arm III (1200mg Polyphenon E) | Absolute Change for Baseline From EGCG in Serum Samples | 85.37 ng/mL | Standard Deviation 76.34 |
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.
Time frame: Baseline and up to 28 days
Population: Analysis was not able to be completed for 3 participants in Arm I and 1 participant in Arm II.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Placebo) | Absolute Change for Baseline of EGCG in Urine Samples | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change for Baseline of EGCG in Urine Samples | 1.93 ng/mL | Standard Deviation 0.98 |
| Arm III (1200mg Polyphenon E) | Absolute Change for Baseline of EGCG in Urine Samples | 3.38 ng/mL | Standard Deviation 1.6 |
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.
Time frame: Baseline and up to 28 days
Population: Analysis was not able to be completed for 3 participants in Arm I and 1 participant in Arm II.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | epicatechin (EC) | 0.52 ng/mL | Standard Deviation 1.46 |
| Arm I (Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | epicatechin gallate (ECG) | 0.00 ng/mL | Standard Deviation 0 |
| Arm I (Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | Epigallocatechin (EGC) | 0.20 ng/mL | Standard Deviation 0.55 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | epicatechin (EC) | 2.41 ng/mL | Standard Deviation 3.15 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | epicatechin gallate (ECG) | 1.13 ng/mL | Standard Deviation 1.78 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | Epigallocatechin (EGC) | 3.60 ng/mL | Standard Deviation 3.21 |
| Arm III (1200mg Polyphenon E) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | epicatechin gallate (ECG) | 1.49 ng/mL | Standard Deviation 2.13 |
| Arm III (1200mg Polyphenon E) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | Epigallocatechin (EGC) | 12.16 ng/mL | Standard Deviation 11.09 |
| Arm III (1200mg Polyphenon E) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E in Urine Samples | epicatechin (EC) | 5.33 ng/mL | Standard Deviation 6.78 |
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.
Time frame: Baseline and up to 28 days
Population: Analysis was not able to be completed for 2 participants in Arm I and 1 participant in Arm II.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epicatechin (EC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm I (Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epicatechin gallate (ECG) | 0.17 ng/mL | Standard Deviation 0.52 |
| Arm I (Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epigallocatechin (EGC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epicatechin (EC) | 0.97 ng/mL | Standard Deviation 1.97 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epicatechin gallate (ECG) | 8.38 ng/mL | Standard Deviation 11.03 |
| Arm II (800mg Polyphenon E, Placebo) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epigallocatechin (EGC) | 6.93 ng/mL | Standard Deviation 10.06 |
| Arm III (1200mg Polyphenon E) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epicatechin gallate (ECG) | 8.62 ng/mL | Standard Deviation 9.14 |
| Arm III (1200mg Polyphenon E) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epigallocatechin (EGC) | 3.46 ng/mL | Standard Deviation 4.04 |
| Arm III (1200mg Polyphenon E) | Absolute Change From Baseline of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Plasma Samples | epicatechin (EC) | 0.31 ng/mL | Standard Deviation 0.66 |
Secondary
Levels of EGCG in Malignant Bladder Tissue
Time frame: up to 28 days
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Placebo) | Levels of EGCG in Malignant Bladder Tissue | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of EGCG in Malignant Bladder Tissue | 0.00 ng/mL | Standard Deviation 0 |
| Arm III (1200mg Polyphenon E) | Levels of EGCG in Malignant Bladder Tissue | 2.54 ng/mL | Standard Deviation 2.92 |
Secondary
Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples
Time frame: up to 28 days
Population: Analysis was not able to be completed for 2 participants in Arm I and 2 participants in Arm III.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epicatechin (EC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm I (Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epicatechin gallate (ECG) | 0.00 ng/mL | Standard Deviation 0 |
| Arm I (Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epigallocatechin (EGC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epicatechin (EC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epicatechin gallate (ECG) | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epigallocatechin (EGC) | 0.20 ng/mL | Standard Deviation 0.55 |
| Arm III (1200mg Polyphenon E) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epicatechin gallate (ECG) | 0.00 ng/mL | Standard Deviation 0 |
| Arm III (1200mg Polyphenon E) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epigallocatechin (EGC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm III (1200mg Polyphenon E) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | epicatechin (EC) | 0.20 ng/mL | Standard Deviation 0.55 |
Secondary
Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples
Time frame: up to 28 days
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epicatechin (EC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm I (Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epicatechin gallate (ECG) | 0.00 ng/mL | Standard Deviation 0 |
| Arm I (Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epigallocatechin (EGC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epicatechin (EC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epicatechin gallate (ECG) | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epigallocatechin (EGC) | 0.00 ng/mL | Standard Deviation 0 |
| Arm III (1200mg Polyphenon E) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epicatechin gallate (ECG) | 0.00 ng/mL | Standard Deviation 0 |
| Arm III (1200mg Polyphenon E) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epigallocatechin (EGC) | 0.60 ng/mL | Standard Deviation 1.58 |
| Arm III (1200mg Polyphenon E) | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | epicatechin (EC) | 0.00 ng/mL | Standard Deviation 0 |
Secondary
Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry
Time frame: up to 28 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | VEGF | 0.011 optical density | Standard Deviation 0.0065 |
| Arm I (Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | Clusterin | 0.074 optical density | Standard Deviation 0.032 |
| Arm I (Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | PCNA | 0.41 optical density | Standard Deviation 0.052 |
| Arm I (Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | MMP2 | 0.16 optical density | Standard Deviation 0.026 |
| Arm I (Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | p27 | 0.36 optical density | Standard Deviation 0.08 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | Clusterin | 0.061 optical density | Standard Deviation 0.02 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | PCNA | 0.38 optical density | Standard Deviation 0.061 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | MMP2 | 0.18 optical density | Standard Deviation 0.054 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | VEGF | 0.021 optical density | Standard Deviation 0.0173 |
| Arm II (800mg Polyphenon E, Placebo) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | p27 | 0.35 optical density | Standard Deviation 0.09 |
| Arm III (1200mg Polyphenon E) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | p27 | 0.31 optical density | Standard Deviation 0.057 |
| Arm III (1200mg Polyphenon E) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | VEGF | 0.013 optical density | Standard Deviation 0.0066 |
| Arm III (1200mg Polyphenon E) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | PCNA | 0.35 optical density | Standard Deviation 0.052 |
| Arm III (1200mg Polyphenon E) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | Clusterin | 0.046 optical density | Standard Deviation 0.013 |
| Arm III (1200mg Polyphenon E) | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | MMP2 | 0.16 optical density | Standard Deviation 0.069 |
Secondary
Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT)
Time frame: At Baseline
Population: This outcome was assessed in all participants,combined irrespective of their randomization.~Analysis was not able to be completed on 4 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | Plasma | 4.12 ng/mL | Standard Deviation 4.8 |
| Arm I (Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | Serum | 0.00 ng/mL | Standard Deviation 0 |
| Arm II (800mg Polyphenon E, Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | Plasma | 0.57 ng/mL | Standard Deviation 1.89 |
| Arm II (800mg Polyphenon E, Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | Serum | 0.69 ng/mL | Standard Deviation 1.82 |
| Arm III (1200mg Polyphenon E) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | Plasma | 2.48 ng/mL | Standard Deviation 3.48 |
| Arm III (1200mg Polyphenon E) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | Serum | 0.43 ng/mL | Standard Deviation 1.21 |
Secondary
Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT)
Time frame: At Baseline
Population: This outcome was assessed in all participants,combined irrespective of their randomization. Analysis was not able to be completed for 4 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Plasma | 2.97 ng/mL | Standard Deviation 4.2 |
| Arm I (Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Urine | 1.72 ng/mL | Standard Deviation 2.43 |
| Arm II (800mg Polyphenon E, Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Urine | 0.86 ng/mL | Standard Deviation 2.27 |
| Arm II (800mg Polyphenon E, Placebo) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Plasma | 2.09 ng/mL | Standard Deviation 3.75 |
| Arm III (1200mg Polyphenon E) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Plasma | 2.02 ng/mL | Standard Deviation 3.58 |
| Arm III (1200mg Polyphenon E) | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Urine | 0.10 ng/mL | Standard Deviation 0.4 |
| 7/7 Genotype | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Plasma | 0.00 ng/mL | Standard Deviation 0 |
| 7/7 Genotype | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | Urine | 0.00 ng/mL | Standard Deviation 0 |
Secondary
Serum IGFBP-3 Levels Assessed by ELISA
Time frame: Baseline and up to 28 days
Population: Analysis was not able to be completed for 2 participants in Arm I.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Serum IGFBP-3 Levels Assessed by ELISA | Baseline | 1918.31 ng/mL | Standard Deviation 607.16 |
| Arm I (Placebo) | Serum IGFBP-3 Levels Assessed by ELISA | End of Study | 2020.31 ng/mL | Standard Deviation 701.46 |
| Arm II (800mg Polyphenon E, Placebo) | Serum IGFBP-3 Levels Assessed by ELISA | Baseline | 1679.61 ng/mL | Standard Deviation 556.59 |
| Arm II (800mg Polyphenon E, Placebo) | Serum IGFBP-3 Levels Assessed by ELISA | End of Study | 1800.08 ng/mL | Standard Deviation 490.92 |
| Arm III (1200mg Polyphenon E) | Serum IGFBP-3 Levels Assessed by ELISA | Baseline | 1824.86 ng/mL | Standard Deviation 559.58 |
| Arm III (1200mg Polyphenon E) | Serum IGFBP-3 Levels Assessed by ELISA | End of Study | 1624.03 ng/mL | Standard Deviation 611.89 |
Secondary
Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA
Time frame: Baseline and up to day 28
Population: Analysis was not able to be completed for 2 participants in Arm I.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Placebo) | Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | Baseline | 135.06 ng/mL | Standard Deviation 22.64 |
| Arm I (Placebo) | Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | End of Study | 131.86 ng/mL | Standard Deviation 15.59 |
| Arm II (800mg Polyphenon E, Placebo) | Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | Baseline | 122.22 ng/mL | Standard Deviation 37.49 |
| Arm II (800mg Polyphenon E, Placebo) | Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | End of Study | 124.22 ng/mL | Standard Deviation 38.06 |
| Arm III (1200mg Polyphenon E) | Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | Baseline | 132.12 ng/mL | Standard Deviation 15.12 |
| Arm III (1200mg Polyphenon E) | Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | End of Study | 132.27 ng/mL | Standard Deviation 27.77 |