Phase II Study of Isoflavone G-2535 (Genistein) in Patien... | NCT00118040

NCT00118040

Secondary IDs

ID	Type	Description	Link
NCI-2013-00453	Registry Identifier	CTRP (Clinical Trial Reporting Program)
CDR0000433520
WCCC-UWI03-1-01
WCCC-CO-04307
UWI03-1-01	Other Identifier	University of Wisconsin Chemoprevention Consortium
UWI03-1-01	Other Identifier	DCP
N01CN35153	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. To measure the effect of G-2535 on EGF-R phosphorylation. Two EGF-R phosphorylation sites with functional significance are phosphotyrosine 992, which is a direct binding site for the PLC-gamma SH2 domain, and phosphotyrosine 1068, a binding site for the Grb2/SH2 domain. The expression of EGF-R and phosphorylated EGF-R will be determined in tumors as well as adjacent and remote normal appearing urothelium.

SECONDARY OBJECTIVES:

I. Measuring tissue intermediate endpoint biomarkers such as EGF-R mutations (EGFR vIII, exon 19-21), Ki67, activated Caspase 3, Akt, P-Akt, MAP kinase, P-MAP kinase, COX-2, survivin, and BLCA-4 and we will also determine survivin and BLCA-4 levels in urine specimens as surrogate tumor markers. Biomarkers associated with the EGF-R pathway, including Akt and P-Akt will be studied by immunohistochemistry. Additionally, Ki67, activated Caspase 3 (as a marker of apoptosis), and COX-2 will serve as biological endpoint biomarkers to measure the effects of G-2535 on proliferation, apoptosis, and other processes and molecules relevant to bladder cancer. These studies will be performed on tumors as well as adjacent and remote normal urothelium. II. Safety will also be studied.

OUTLINE: This is a randomized, placebo-controlled, multicenter study. Patients are stratified according to invasiveness of disease (non-invasive [stage Ta, Tis, or T1] vs invasive [stage T2, T3, or T4]). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive oral genistein twice daily for approximately 14-30 days.

Arm II: Patients receive oral genistein as in arm I but at a higher dose. Arm III: Patients receive oral placebo twice daily for approximately 14-30 days.

One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Patients undergo blood, urine, and tissue sample collection for pharmacogenomic, pharmacokinetic, and biomarker laboratory studies. Blood and urine samples are collected at baseline, after 1 week of treatment, and at the time of surgery for pharmacokinetic and urine biomarker (survivin and BLCA-4) studies. Pharmacogenomic studies (epidermal growth factor receptor [EGFR] polymorphisms and CYP3A 4/5 genotypes) are performed at baseline using blood samples. Tissue biomarker (EGFR polymorphism, EGFR mutations [EGFR vIII, exon 19-21], EGFR, phosphorylated EGFR, Ki67, activated caspase 3, Akt, P-Akt, MAP kinase, P-MAP kinase, COX-2, survivin, and BLCA4) studies using tumor tissue and adjacent and remote normal urothelium are performed at baseline and at the completion of treatment.

PROJECTED ACCRUAL: A total of 60 patients (20 per treatment arm) will be accrued for this study within 1 year.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm I (lower dose genistein)	Experimental	Patients receive oral genistein twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.	Drug: Genistein Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Therapeutic Conventional Surgery
Arm II (higher dose genistein)	Experimental	Patients receive oral genistein as in arm I but at a higher dose. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.	Drug: Genistein Other: Laboratory Biomarker Analysis Other: Pharmacological Study Procedure: Therapeutic Conventional Surgery
Arm III (placebo)	Placebo Comparator	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.	Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Placebo Administration Procedure: Therapeutic Conventional Surgery

Name	Type	Description	Arm Group Labels	Other Names
Genistein	Drug	Given orally	Arm I (lower dose genistein) Arm II (higher dose genistein)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment	Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.	up to 21 days
pEGFR in Benign Tissue	Detecting the signal of the biomarker, pEGFR, in the benign tissue after being on study drug for between 14-21 days. Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.	up to 21 days on Study Drug

Secondary Outcomes

Measure	Description	Time Frame
BLCA-4 in Urine by Visit	Detecting the mean amount of the biomarker BLCA-4 in the urine of patients prior to starting study agent, at Day 8 and pre-surgery time (when they have been on study agent between 14-21 days). This is measured by urine analysis at each of the time points to serve as a surrogate tumor marker.	up to 21 days

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants eligible for this study will have been evaluated by diagnostic office cystoscopy and found to have a bladder tumor; enrollment (signing of the consent form) must be within 60 days of pre-study cystoscopy demonstrating bladder tumor; the participant should have no evidence of distant metastasis and the primary tumor may represent either an initial diagnosis or recurrent disease of any clinical stage. Study participants must also be candidates for either subsequent cystoscopy/transurethral resection of bladder tumor (TURBT) or complete or partical cystectomy; histologic diagnosis is not required for enrollment; pre-enrollment diagnostic cystoscopy must be at least 45 days after treatment of the bladder with other agents such as BCG (participants with recurrent disease)
ECOG performance status 0 or 1
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
Ability to understand and the willingness to sign a written informed consent document
WBC >= 3000/mm^3
Platelets >= 100,000mm^3
Hemoglobin >= 10 g/dL
Bilirubin =< 1.4 mg/dl
AST =< 3x normal
Creatinine =< 2.0mg/dl
Serum calcium =< 10.2 mg/dl,
Amylase =< 3 x normal
Na >= 125 and =< 155 mmol/L
K >= 3.2 and =< 6 mmol/L
Cl >= 85 and =< 114 mmol/L
CO2 >= 11 mEQ/dL
TSH within 1.3 x the upper range of normal and normal T4
Females of child-bearing potential must have a negative pregnancy test; patients who have had a bilateral oophorectomy, hysterectomy, are greater than 1 year since their last menses, or are greater than 51 years of age are not considered to be of child-baring potential
Participants must agree to stop soy supplements before enrolling in the study
Patients must agree to stop taking NSAIDS before enrolling in the study; patients may, however, take cardioprotective doses of aspirin equal to or less than 81mg per day

Exclusion Criteria:

Participant may not have received other treatment for bladder cancer between the pre-enrollment cystoscopy and subsequent surgery
Participants may not be receiving any other investigational agents
Participant may not have received prior pelvic irradiation for any reason
Participant may not be receiving concurrent systemic cancer treatment for other cancers
Participant may not be taking concurrent soy supplements while on the study medication
Participant may not be taking concurrent NSAIDS (aspirin doses of =< 81 mg acceptable) while on the study medication
Participant may not be taking thyroid medications
History of allergic reactions attributed to compounds of similar chemical or biologic composition to genistein, soy isoflavones or other allergies to soy-based products will render a participant ineligible
Uncontrolled concurrent illness will render a participant ineligible including, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unregulated cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Women may not be pregnant or lactating; the effects of G-2535 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Contacts/Locations Module

Name	Affiliation	Role
Howard H Bailey	University of Wisconsin Chemoprevention Consortium	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham Cancer Center		Birmingham	Alabama	35233	United States
South Orange County Surgical Medical Group Inc

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22293631	Derived	Messing E, Gee JR, Saltzstein DR, Kim K, diSant'Agnese A, Kolesar J, Harris L, Faerber A, Havighurst T, Young JM, Efros M, Getzenberg RH, Wheeler MA, Tangrea J, Parnes H, House M, Busby JE, Hohl R, Bailey H. A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients. Cancer Prev Res (Phila). 2012 Apr;5(4):621-30. doi: 10.1158/1940-6207.CAPR-11-0455. Epub 2012 Jan 31.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
FG001	Arm II (600mg Genistein)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

4'',5, 7-Trihydroxyisoflavone

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
BG001	Arm II (600mg Genistein)	Patients receive oral genistein as in arm I but at a higher dose (600mg). One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
BG002	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00020 BG00120 BG00220 BG00360

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00068.60± 9.16 BG00168.65± 9.16 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0005 BG0011 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00020 BG00120 BG002

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

Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

For this outcome Arm 1 and Arm II were analyzed together which lead to Arm IV. Also for Arm III although 14 participants successfully completed the study for this group they were able to analyzed 15 for this outcome.

Posted

Number

percentage of pEGFR strength signal

up to 21 days

ID	Title	Description
OG000	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG001	Arm II (600mg Genistein)	Patients receive oral genistein as in arm I but at a higher dose (600mg). One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG003	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein

Units	Counts
Participants	OG00019 OG00118 OG00215 OG003

Title

Denominators

Categories

Strong

Title	Measurements
	OG00052.63 OG00183.33 OG00293.33 OG003

Secondary

BLCA-4 in Urine by Visit

Detecting the mean amount of the biomarker BLCA-4 in the urine of patients prior to starting study agent, at Day 8 and pre-surgery time (when they have been on study agent between 14-21 days). This is measured by urine analysis at each of the time points to serve as a surrogate tumor marker.

Posted

Mean

Standard Deviation

pg/ml

up to 21 days

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

Survivin in Urine by Visit (pg/ml)

Detecting the mean amount of the biomarker Survivin in the urine of patients prior to starting study agent, at Day 8 and pre-surgery time (when they have been on study agent between 14-21 days). This is measured by urine analysis at each of the time points to serve as a surrogate tumor marker.

Posted

Mean

Standard Deviation

pg/ml

up to 21 days

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

Survivin in Tumor Tissue

Detecting the signal of the biomarker, Survivin, in the tumor tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of Survivin strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

EGFR Mutations in Tumor Tissue

Detecting the signal of EGFR mutations in the tumor tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of EGFR strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Primary

pEGFR in Benign Tissue

Detecting the signal of the biomarker, pEGFR, in the benign tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

For this outcome Arm 1 and Arm II were analyzed together which lead to Arm IV.

Posted

Number

percentage of pEGFR strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

EGFR in Benign Tissue

Detecting the signal of the biomarker, EGFR, in the benign tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

For this outcome Arm 1 and Arm II were analyzed together which lead to Arm IV.

Posted

Number

percentage of EGFR strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

Ki-67 in Tumor Tissue

Detecting the signal of the biomarker, Ki-67, in the tumor tissue after being on study drug for between 14-21 days as a way to measuring the effects G-2535 have on it with regards to proliferation, apoptosis, and other processes relevant to bladder cancer.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of Ki-67 strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

Activated Caspase 3 in Tumor Tissue

Detecting the signal of the biomarker, Activated Caspase 3, in the tumor tissue after being on study drug for between 14-21 days as a way to measuring the effects G-2535 have on it with regards to proliferation, apoptosis, and other processes relevant to bladder cancer.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of Caspase 3 strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)

Secondary

COX2 in Tumor Tissue

Detecting the signal of the biomarker, COX2, in the tumor tissue after being on study drug for between 14-21 days as a way to measuring the effects G-2535 have on it with regards to proliferation, apoptosis, and other processes relevant to bladder cancer.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of COX2 strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

AKT in Tumor Tissue

Detecting the signal of the biomarker, AKT, in the tumor tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of AKT strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

pAKT in Tumor Tissue

Detecting the signal of the biomarker, pAKT, in the tumor tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of pAKT strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

MAP Kinase in Tumor Tissue

Detecting the signal of the biomarker, MAP Kinase, in the tumor tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of MAP Kinase strength signal

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Secondary

pMAP Kinase in Tumor Tissue

Detecting the signal of the biomarker, pMAP Kinase, in the tumor tissue after being on study drug for between 14-21 days.

Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

Posted

Number

percentage of pMAP Kinase strength signa

up to 21 days on Study Drug

ID	Title	Description
OG000	Arm IV (300mg Genistein + 600mg Genistein)	This is a combination analysis those on 300mg of genistein and 600mg genistein
OG001	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.
OG002	Arm I (300mg Genistein)	Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm I (Lower Dose Genistein)	Patients receive oral genistein twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy. genistein: Given orally laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy. pharmacological study: Correlative studies	1	20	18	20
EG001	Arm II (Higher Dose Genistein)	Patients receive oral genistein as in arm I but at a higher dose. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy. genistein: Given orally laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy. pharmacological study: Correlative studies	0	20	17	20
EG002	Arm III (Placebo)	Patients receive oral placebo twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy. laboratory biomarker analysis: Correlative studies placebo: Given orally therapeutic conventional surgery: Undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy. pharmacological study: Correlative studies	0	20	12	20

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Supraventricular arrhythmia- Supraventricular tachycardia	Cardiac disorders	CTCAE (3.0)	Systematic Assessment		EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	Social circumstances	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
Sweating	Social circumstances	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Itiching	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Rash	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Urticaria	Skin and subcutaneous tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Diabetes	Endocrine disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Hypothyroidism	Endocrine disorders	CTCAE (3.0)	Systematic Assessment	EG0004 events4 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Constipation	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected20 at risk EG0023 events2 affected20 at risk
Dry Mouth	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Flatulence	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected20 at risk EG0021 events1 affected20 at risk
Heartburn	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0021 events1 affected20 at risk
Nausea	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Infection of brochus	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
Infection of upper airway	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Infection of urinary tract	Infections and infestations	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
amylase	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected20 at risk EG0024 events3 affected20 at risk
Bicarbonate, serum low	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected20 at risk EG0023 events3 affected20 at risk
Elevated Bilirubin	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
Creatinine	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
decreased bilirubin	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
decreased bun	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Elevated bun	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0004 events4 affected20 at risk EG0011 events1 affected20 at risk EG0021 events1 affected20 at risk
Elevated Chloride	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected20 at risk EG0022 events2 affected20 at risk
High chloride	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
hypercalcemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Hyperkalemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
hypoalbuminemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Hypocalcemia	Gastrointestinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk EG0023 events3 affected20 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
hypoatremia	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
lipase	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0006 events6 affected20 at risk EG0011 events1 affected20 at risk EG0022 events2 affected20 at risk
low chloride	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
low creatinine	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
low protein in blood work	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Low total bilirubin	Metabolism and nutrition disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Fracture	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Fullness in left jaw area	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
muscle weakness extremity-upper	Musculoskeletal and connective tissue disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
Syncope	Nervous system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
Back Pain	General disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
headache	General disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
pain: Breast	General disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
Pain: Esophagus	General disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
Pain: Muscle	General disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
excess phlegm	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
urinary frequency	Renal and urinary disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
urinary retention	Renal and urinary disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
lupus	Immune system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
rhinitis	Immune system disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
decreased red blood cells	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk
elevated hematocrit	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
elevated platelets	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
elevated white blood cells	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
high platelets	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
hemoglobin	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0002 events2 affected20 at risk EG0012 events2 affected20 at risk EG0022 events2 affected20 at risk
leukocytes	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0020 events0 affected20 at risk
low hematocrit	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected20 at risk EG0021 events1 affected20 at risk
platelets	Blood and lymphatic system disorders	CTCAE (3.0)	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk EG0020 events0 affected20 at risk
hypertension	Cardiac disorders	CTCAE (3.0)	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk EG0021 events1 affected20 at risk

ID	Term
D001749	Urinary Bladder Neoplasms

Ancestor Terms

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

ID	Term
D019833	Genistein

Ancestor Terms

ID	Term
D007529	Isoflavones
D005419	Flavonoids
D002867	Chromones
D001578	Benzopyrans
D011714	Pyrans
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

Patients receive oral genistein (150mg) twice daily for approximately 14-30 days. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.