Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00906 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CO06810 | |||
| CDR0000594276 | |||
| H-2007-0250 | |||
| UWI06-8-01 | Other Identifier | University of Wisconsin Hospital and Clinics | |
| UWI06-8-01 | Other Identifier | DCP | |
| N01CN35153 | U.S. NIH Grant/Contract | View source | |
| P30CA014520 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I (placebo) | Placebo Comparator | Patients receive six oral placebo capsules once daily for 14-28 days. |
|
| Arm II (polyphenon E, placebo) | Experimental | 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 (polyphenon E, trans-urethral resection or cystectomy) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Defined Green Tea Catechin Extract | Dietary Supplement | Given orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Tracy Downs | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham Cancer Center | Birmingham | Alabama | 35233 | United States | ||
| Lahey Hospital and Medical Center |
Not provided
Participants were recruited during a 4 year period by staff at 5 participating institutions (both University hospitals and community clinics).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Pharmacological Study | Other | Correlative studies |
|
| Placebo | Drug | Given orally |
|
|
| Therapeutic Conventional Surgery | Procedure | Undergo surgery |
|
| 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 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 |
| 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 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 |
| 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 |
| 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 |
| Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | At Baseline |
| Burlington |
| Massachusetts |
| 01805 |
| United States |
| Minneapolis Veterans Medical Center | Minneapolis | Minnesota | 55417 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| Urology San Antonio Research PA | San Antonio | Texas | 78229 | United States |
| University of Wisconsin Hospital and Clinics | Madison | Wisconsin | 53792 | United States |
| 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 |
| FG002 | 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 |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Error | ng/mL | up to 28 days |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Levels of EGCG in Malignant Bladder Tissue | Analysis was not able to be completed for 1 participant in Arm I, 1 participant in Arm II, and 3 participants in Arm III. | Posted | Mean | Standard Deviation | ng/mL | up to 28 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Levels of Surrogate Intermediate Endpoint Biomarkers in Malignant and Nonmalignant Bladder Tissue Assessed by Immunohistochemistry | Posted | Mean | Standard Deviation | optical density | up to 28 days |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Serum Insulin Growth Factor-1 (IGF-1) Levels Assessed by ELISA | Analysis was not able to be completed for 2 participants in Arm I. | Posted | Mean | Standard Deviation | ng/mL | Baseline and up to day 28 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Tumor Tissue Samples | Analysis was not able to be completed for 1 participant in Arm I, 1 participant in Arm II, and 3 participants in Arm III. | Posted | Mean | Standard Deviation | ng/mL | 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. | Analysis was not able to be completed for 2 participants in Arm I and 1 participant in Arm II. | Posted | Mean | Standard Deviation | ng/mL | Baseline and up to 28 days |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Catechol-O-Methyltransferase (COMT) | This outcome was assessed in all participants,combined irrespective of their randomization. Analysis was not able to be completed on 4 participants. | Posted | Mean | Standard Deviation | ng/mL | At Baseline |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Serum IGFBP-3 Levels Assessed by ELISA | Analysis was not able to be completed for 2 participants in Arm I. | Posted | Mean | Standard Deviation | ng/mL | Baseline and up to 28 days |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Levels of Other Catechins (Epicatechin Gallate, Epicatechin, and Epigallocatechin) Found in Polyphenon E Normal Tissue Samples | Analysis was not able to be completed for 2 participants in Arm I and 2 participants in Arm III. | Posted | Mean | Standard Deviation | ng/mL | 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. | Analysis was not able to be completed for 3 participants in Arm I and 1 participant in Arm II. | Posted | Mean | Standard Deviation | ng/mL | 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. | Analysis was not able to be completed for 2 participants in Arm I and 1 participant in Arm II. | Posted | Mean | Standard Deviation | ng/mL | 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. | Analysis was not able to be completed for 3 participants in Arm I and 1 participant in Arm II. | Posted | Mean | Standard Deviation | ng/mL | Baseline and up to 28 days |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Metabolism of EGCG in Serum and Urine in Relation to Pharmacogenetic Polymorphisms in Uridinediphosphate- Glucuronosyltransferase (UGT) | This outcome was assessed in all participants,combined irrespective of their randomization. Analysis was not able to be completed for 4 participants. | Posted | Mean | Standard Deviation | ng/mL | At Baseline |
|
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 0 | 11 | 3 | 11 | ||
| EG001 | 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 | 0 | 10 | 5 | 10 | ||
| EG002 | 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 | 0 | 10 | 6 | 10 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tinnitus | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Flushing | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| pruritus | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| heartburn | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Nausa | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| taste alteration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Urinary Tract infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
| |
| imb | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
| |
| hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
| |
| photophobia | Eye disorders | CTCAE (3.0) | Systematic Assessment |
| |
| abdominal pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| anal pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| |
| back pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| extremity limb pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| headache | General disorders | CTCAE (3.0) | Systematic Assessment |
| |
| joint pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| kidney pain | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
| |
| muscle pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
| |
| pelvis pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Howard H. Bailey | University of Wisconsin | 608-263-8624 | hhbailey@wisc.edu |
| ID | Term |
|---|---|
| D001749 | Urinary Bladder Neoplasms |
| ID | Term |
|---|---|
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C472086 | polyphenon E |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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
|
|
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
|
|
|
|
|