Genistein in Patients Who Are Undergoing Surgery for Bladder Cancer
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Bladder Cancer |
Dietary Supplement: genistein Other: placebo |
Phase 2 |
| Study Type: | Interventional |
| 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 ]
| Estimated Enrollment: | 60 |
| Study Start Date: | June 2005 |
| Study Completion Date: | August 2010 |
| Primary Completion Date: | June 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients receive oral genistein twice daily for approximately 14-30 days.
|
Dietary Supplement: genistein
Given orally
|
|
Experimental: Arm II
Patients receive oral genistein as in arm I but at a higher dose.
|
Dietary Supplement: genistein
Given orally
|
|
Placebo Comparator: Arm III
Patients receive oral placebo twice daily for approximately 14-30 days.
|
Other: placebo
Given orally
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| 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 |
More Information
Additional Information:
No publications provided by University of Wisconsin, Madison
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Edward G. Shaw, Wake Forest University Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00118040 History of Changes |
| Other Study ID Numbers: | CDR0000433520, P30CA014520, WCCC-CO-04307, WCCC-UWI03-1-01, WCCC-H-2005-0026 |
| Study First Received: | July 8, 2005 |
| Last Updated: | August 31, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Wisconsin, Madison:
|
stage 0 bladder cancer recurrent bladder cancer stage I bladder cancer |
stage II bladder cancer stage III bladder cancer stage IV bladder cancer |
Additional relevant MeSH terms:
|
Urinary Bladder Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplasms Urinary Bladder Diseases Urologic Diseases Genistein Phytoestrogens Estrogens, Non-Steroidal Estrogens |
Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Anticarcinogenic Agents Protective Agents Antineoplastic Agents Therapeutic Uses Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 19, 2013