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.
Allocation: Randomized, Primary Purpose: Treatment
Epidermal growth factor receptor (EGFR) phosphorylation in tumor tissue, as measured by immunohistochemistry after the completion of treatment
Edward M. Messing, MD, FACS
James P. Wilmot Cancer Center
United States: Food and Drug Administration
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center||Madison, Wisconsin 53792-6164|
|Orange County Urology Associates, Incorporated||Laguna Hills, California 92653|