Genistein in Patients Who Are Undergoing Surgery for Bladder Cancer - Full Text View

Sponsors and Collaborators:	University of Wisconsin, Madison National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00118040

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 II

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer Surgery Urine and Urination

Drug Information available for: Genistein

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Placebo Control
Official Title:	Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Epidermal growth factor receptor (EGFR) phosphorylation in tumor tissue, as measured by immunohistochemistry after the completion of treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

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
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive oral genistein twice daily for approximately 14-30 days.	Dietary Supplement: genistein Given orally
Arm II: Experimental Patients receive oral genistein as in arm I but at a higher dose.	Dietary Supplement: genistein Given orally
Arm III: Placebo Comparator 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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118040

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

Sponsors and Collaborators

University of Wisconsin, Madison

National Cancer Institute (NCI)

Investigators

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Wake Forest University Comprehensive Cancer Center ( Edward G. Shaw )
Study ID Numbers:	CDR0000433520, WCCC-CO-04307, WCCC-UWI03-1-01, WCCC-H-2005-0026
Study First Received:	July 8, 2005
Last Updated:	April 6, 2009
ClinicalTrials.gov Identifier:	NCT00118040 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage 0 bladder cancer
recurrent bladder cancer
stage I bladder cancer

stage II bladder cancer
stage III bladder cancer
stage IV bladder cancer

Study placed in the following topic categories:

Anticarcinogenic Agents
Urinary Tract Neoplasm
Estrogens
Cystocele
Hormone Antagonists
Urinary Bladder Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Urinary Bladder Neoplasms
Urogenital Neoplasms

Urologic Neoplasms
Protein Kinase Inhibitors
Hormones
Recurrence
Urologic Diseases
Phytoestrogens
Bladder Neoplasm
Genistein

Additional relevant MeSH terms:

Anticarcinogenic Agents
Estrogens
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors
Urogenital Neoplasms
Urologic Neoplasms

Protein Kinase Inhibitors
Protective Agents
Hormones
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Urologic Diseases
Estrogens, Non-Steroidal
Therapeutic Uses
Phytoestrogens
Genistein

ClinicalTrials.gov processed this record on May 07, 2009