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Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer

Phase 2
18 Years
Not Enrolling
Bladder Cancer

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Trial Information

Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer



- Compare the effect of genistein vs placebo on epidermal growth factor receptor (EGFR)
phosphorylation, as measured by immunohistochemistry, in patients undergoing surgical
resection for bladder cancer.


- Measure tissue intermediate endpoint biomarkers, such as EGFR mutations (EGFR vIII,
exon 19-21), Ki67, activated caspase 3, Akt, P-Akt, MAP kinase, P-MAP kinase, COX-2,
survivin, and BLCA-4, in tumor tissue and adjacent and remote normal urothelium.

- Determine survivin and BLCA-4 levels in urine specimens as surrogate tumor markers.

- Compare the safety of genistein vs placebo in these patients.

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.

Inclusion Criteria


- Diagnosis of primary bladder cancer by cystoscopy within the past 60 days*

- Initial diagnosis or recurrent disease

- Any clinical stage NOTE: *Diagnostic cystoscopy must be performed ≥ 45 days
after treatment with BCG or other agents for bladder cancer (for patients with
recurrent disease)

- Candidate for subsequent cystoscopic excision, transurethral resection of the bladder
tumor, or complete or partial cystectomy

- No evidence of distant metastasis



- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- Not specified


- WBC ≥ 3,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL


- Bilirubin ≤ 1.4 mg/dL

- AST ≤ 3 times normal

- Amylase ≤ 3 times normal


- Creatinine ≤ 2.0 mg/dL

- Calcium ≤ 10.2 mg/dL


- No symptomatic congestive heart failure

- No unstable angina pectoris

- No uncontrolled cardiac arrhythmia


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Sodium 125-155 mmol/L

- Potassium 3.2-6 mmol/L

- Chloride 85-114 mmol/L

- Carbon dioxide ≥ 11 mEq/dL

- Thyroid-stimulating hormone < 1.3 times upper limit of normal

- Total T4 normal

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to genistein or soy isoflavones

- No other allergy to soy-based products

- No active or ongoing infection

- No psychiatric illness or social situation that would preclude study compliance

- No other uncontrolled illness


Biologic therapy

- See Disease Characteristics


- Not specified

Endocrine therapy

- Not specified


- No prior pelvic irradiation


- See Disease Characteristics


- No other concurrent investigational agents

- No other concurrent soy supplements

- No concurrent thyroid medications

- No concurrent non-steroidal anti-inflammatory drugs, including aspirin

- Concurrent cardioprotective doses of aspirin (≤ 81 mg/day) allowed

- No other concurrent systemic anticancer therapy

- No other concurrent treatment for bladder cancer between the pre-enrollment
cystoscopy and subsequent surgery

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Epidermal growth factor receptor (EGFR) phosphorylation in tumor tissue, as measured by immunohistochemistry after the completion of treatment

Safety Issue:


Principal Investigator

Edward M. Messing, MD, FACS

Investigator Role:

Study Chair

Investigator Affiliation:

James P. Wilmot Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2005

Completion Date:

August 2010

Related Keywords:

  • Bladder Cancer
  • stage 0 bladder cancer
  • recurrent bladder cancer
  • stage I bladder cancer
  • stage II bladder cancer
  • stage III bladder cancer
  • stage IV bladder cancer
  • Urinary Bladder Neoplasms



University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
Orange County Urology Associates, Incorporated Laguna Hills, California  92653