Genistein in Patients Who Are Undergoing Surgery for Bladder Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00118040
First received: July 8, 2005
Last updated: August 31, 2010
Last verified: August 2010
  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

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

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
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
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
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:
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
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 29, 2014