Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer
18 Years
N/A
Both
Bladder Cancer
Trial Information
Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer
OBJECTIVES:
Primary
- 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.
Secondary
- 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
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- WBC ≥ 3,000/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL
Hepatic
- Bilirubin ≤ 1.4 mg/dL
- AST ≤ 3 times normal
- Amylase ≤ 3 times normal
Renal
- Creatinine ≤ 2.0 mg/dL
- Calcium ≤ 10.2 mg/dL
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
Other
- 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
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- Not specified
Endocrine therapy
- Not specified
Radiotherapy
- No prior pelvic irradiation
Surgery
- See Disease Characteristics
Other
- 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:
Interventional
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:
No
Principal Investigator
Edward M. Messing, MD, FACS
Investigator Role:
Study Chair
Investigator Affiliation:
James P. Wilmot Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000433520
NCT ID:
NCT00118040
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
Name | Location |
|---|---|
| University of Wisconsin Paul P. Carbone Comprehensive Cancer Center | Madison, Wisconsin 53792-6164 |
| Orange County Urology Associates, Incorporated | Laguna Hills, California 92653 |
