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

July 8, 2005
August 31, 2010
June 2005
June 2008   (final data collection date for primary outcome measure)
Epidermal growth factor receptor (EGFR) phosphorylation in tumor tissue, as measured by immunohistochemistry after the completion of treatment [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00118040 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Genistein in Patients Who Are Undergoing Surgery for Bladder Cancer
Phase II Study of Isoflavone G-2535 (Genistein) in Patients With 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.

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.

Interventional
Phase 2
Allocation: Randomized
Primary Purpose: Treatment
Bladder Cancer
  • Dietary Supplement: genistein
    Given orally
  • Other: placebo
    Given orally
  • Experimental: Arm I
    Patients receive oral genistein twice daily for approximately 14-30 days.
    Intervention: Dietary Supplement: genistein
  • Experimental: Arm II
    Patients receive oral genistein as in arm I but at a higher dose.
    Intervention: Dietary Supplement: genistein
  • Placebo Comparator: Arm III
    Patients receive oral placebo twice daily for approximately 14-30 days.
    Intervention: Other: placebo
Messing E, Gee JR, Saltzstein DR, Kim K, diSant'Agnese A, Kolesar J, Harris L, Faerber A, Havighurst T, Young JM, Efros M, Getzenberg RH, Wheeler MA, Tangrea J, Parnes H, House M, Busby JE, Hohl R, Bailey H. A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients. Cancer Prev Res (Phila). 2012 Apr;5(4):621-30. doi: 10.1158/1940-6207.CAPR-11-0455. Epub 2012 Jan 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
August 2010
June 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00118040
CDR0000433520, P30CA014520, WCCC-CO-04307, WCCC-UWI03-1-01, WCCC-H-2005-0026
Not Provided
Edward G. Shaw, Wake Forest University Comprehensive Cancer Center
University of Wisconsin, Madison
National Cancer Institute (NCI)
Study Chair: Edward M. Messing, MD, FACS James P. Wilmot Cancer Center
Principal Investigator: Howard H. Bailey, MD University of Wisconsin, Madison
University of Wisconsin, Madison
August 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP