Phase II Study of Isoflavone G-2535 (Genistein) in Patients With Bladder Cancer

NCT00118040 | Completed Phase 2 Results

• 6 other identifiers: NCI-2013-00453CDR0000433520WCCC-UWI03-1-01WCCC-CO-04307UWI03-1-01N01CN35153
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

Brief Summary

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. This randomized phase II trial is studying genistein or placebo to compare how they work in patients who are undergoing surgery for bladder cancer.

Conditions

Recurrent Bladder Carcinoma; Stage I Bladder Cancer AJCC v6 and v7; Stage II Bladder Cancer AJCC v6 and v7; Stage III Bladder Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (2)

• Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment

  Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

  up to 21 days

• pEGFR in Benign Tissue

  Detecting the signal of the biomarker, pEGFR, in the benign tissue after being on study drug for between 14-21 days. Strong, Moderate, Weak, and Negative are categorized based on the signal. The measurements display the strength of the signal between the different Arms.

  up to 21 days on Study Drug

Secondary Outcomes (12)

• BLCA-4 in Urine by Visit

  up to 21 days

• Survivin in Urine by Visit (pg/ml)

  up to 21 days

• Survivin in Tumor Tissue

  up to 21 days on Study Drug

• EGFR Mutations in Tumor Tissue

  up to 21 days on Study Drug

• EGFR in Benign Tissue

  up to 21 days on Study Drug

Study Arms (3)

Arm I (lower dose genistein)

EXPERIMENTAL

Patients receive oral genistein 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.

Drug: Genistein; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Arm II (higher dose genistein)

EXPERIMENTAL

Patients receive oral genistein as in arm I but at a higher dose. One day after completion of genistein or placebo, all patients undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Drug: Genistein; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery

Arm III (placebo)

PLACEBO COMPARATOR

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.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo Administration; Procedure: Therapeutic Conventional Surgery

Interventions

Genistein DRUG

Given orally

Also known as: 4'',5, 7-Trihydroxyisoflavone, Genestein, Genisteol, Prunetol

Arm I (lower dose genistein); Arm II (higher dose genistein)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (lower dose genistein); Arm II (higher dose genistein); Arm III (placebo)

Pharmacological Study OTHER

Correlative studies

Arm I (lower dose genistein); Arm II (higher dose genistein); Arm III (placebo)

Placebo Administration OTHER

Given orally

Arm III (placebo)

Therapeutic Conventional Surgery PROCEDURE

Undergo cystoscopic excision, transurethral resection of the bladder tumor, or cystectomy.

Arm I (lower dose genistein); Arm II (higher dose genistein); Arm III (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants eligible for this study will have been evaluated by diagnostic office cystoscopy and found to have a bladder tumor; enrollment (signing of the consent form) must be within 60 days of pre-study cystoscopy demonstrating bladder tumor; the participant should have no evidence of distant metastasis and the primary tumor may represent either an initial diagnosis or recurrent disease of any clinical stage. Study participants must also be candidates for either subsequent cystoscopy/transurethral resection of bladder tumor (TURBT) or complete or partical cystectomy; histologic diagnosis is not required for enrollment; pre-enrollment diagnostic cystoscopy must be at least 45 days after treatment of the bladder with other agents such as BCG (participants with recurrent disease)
• ECOG performance status 0 or 1
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document
• WBC \>= 3000/mm\^3
• Platelets \>= 100,000mm\^3
• Hemoglobin \>= 10 g/dL
• Bilirubin =\< 1.4 mg/dl
• AST =\< 3x normal
• Creatinine =\< 2.0mg/dl
• Serum calcium =\< 10.2 mg/dl,
• Amylase =\< 3 x normal
• Na \>= 125 and =\< 155 mmol/L
• K \>= 3.2 and =\< 6 mmol/L
• Cl \>= 85 and =\< 114 mmol/L

You may not qualify if:

• Participant may not have received other treatment for bladder cancer between the pre-enrollment cystoscopy and subsequent surgery
• Participants may not be receiving any other investigational agents
• Participant may not have received prior pelvic irradiation for any reason
• Participant may not be receiving concurrent systemic cancer treatment for other cancers
• Participant may not be taking concurrent soy supplements while on the study medication
• Participant may not be taking concurrent NSAIDS (aspirin doses of =\< 81 mg acceptable) while on the study medication
• Participant may not be taking thyroid medications
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to genistein, soy isoflavones or other allergies to soy-based products will render a participant ineligible
• Uncontrolled concurrent illness will render a participant ineligible including, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unregulated cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Women may not be pregnant or lactating; the effects of G-2535 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (10)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

South Orange County Surgical Medical Group Inc

Laguna Hills, California, 92653, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

AccuMed Research Associates

Garden City, New York, 11530, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Urology San Antonio Research PA

San Antonio, Texas, 78229, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

University of Wisconsin Chemoprevention Consortium

Madison, Wisconsin, 53706-1969, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

ProHealth Waukesha Memorial Hospital

Waukesha, Wisconsin, 53188, United States

Location

Related Publications (1)

• 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.

  PMID: 22293631 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Genistein

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Isoflavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Howard H. Bailey, M.D.
• Organization: University of Wisconsin

hhbailey@wisc.edu

608-263-8624

Study Officials

• Howard H Bailey

  University of Wisconsin Chemoprevention Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2005
• First Posted: July 11, 2005
• Study Start: June 24, 2005
• Primary Completion: August 15, 2010
• Study Completion: August 15, 2010
• Last Updated: June 10, 2021
• Results First Posted: March 24, 2016

Record last verified: 2021-03

Locations

US (10)