Genistein in Patients Who Are Undergoing Surgery for Bladder Cancer
RATIONALE: Studying samples of blood, urine, and tissue from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors learn how genistein or placebo works in patients with bladder cancer.
PURPOSE: This randomized phase II trial is studying genistein or placebo to compare how they work in patients who are undergoing surgery for bladder cancer.
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer|
- Epidermal growth factor receptor (EGFR) phosphorylation in tumor tissue, as measured by immunohistochemistry after the completion of treatment [ Designated as safety issue: No ]
- 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, cyclooxygenase-2, survivin, and BLCA-4 [ Designated as safety issue: No ]
- Survivin and BLCA-4 levels in urine specimens [ Designated as safety issue: No ]
- Safety [ Designated as safety issue: Yes ]
|Study Start Date:||June 2005|
|Study Completion Date:||August 2010|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral genistein twice daily for approximately 14-30 days.
Dietary Supplement: genistein
Experimental: Arm II
Patients receive oral genistein as in arm I but at a higher dose.
Dietary Supplement: genistein
Placebo Comparator: Arm III
Patients receive oral placebo twice daily for approximately 14-30 days.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00118040
|United States, California|
|Orange County Urology Associates, Incorporated|
|Laguna Hills, California, United States, 92653|
|United States, Wisconsin|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center|
|Madison, Wisconsin, United States, 53792|
|Study Chair:||Edward M. Messing, MD, FACS||James P. Wilmot Cancer Center|
|Principal Investigator:||Howard H. Bailey, MD||University of Wisconsin, Madison|