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Recurrent Bladder CarcinomaPhase 2NCT00118040

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

A Phase 2 study testing Genistein, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Bladder Carcinoma and Stage I Bladder Cancer AJCC v6 and v7, run by National Cancer Institute (NCI) at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Genistein, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
10 sitesUnited States
Study dates
24 Jun 2005to 15 Aug 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • CO2 >= 11 mEQ/dL
  • TSH within 1.3 x the upper range of normal and normal T4
  • Females of child-bearing potential must have a negative pregnancy test; patients who have had a bilateral oophorectomy, hysterectomy, are greater than 1 year since their last menses, or are greater than 51 years of age are not considered to be of child-baring potential
  • Participants must agree to stop soy supplements before enrolling in the study
  • Patients must agree to stop taking NSAIDS before enrolling in the study; patients may, however, take cardioprotective doses of aspirin equal to or less than 81mg per day

Who cannot join

  • 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
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  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • AccuMed Research Associates

    Garden City, New York, 11530

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • South Orange County Surgical Medical Group Inc

    Laguna Hills, California, 92653

  • University of Wisconsin Chemoprevention Consortium

    Madison, Wisconsin, 53706-1969

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • University of Rochester

    Rochester, New York, 14642

  • Urology San Antonio Research PA

    San Antonio, Texas, 78229

  • ProHealth Waukesha Memorial Hospital

    Waukesha, Wisconsin, 53188

Other trials in United States

About this study

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To measure the effect of G-2535 on EGF-R phosphorylation. Two EGF-R phosphorylation sites with functional significance are phosphotyrosine 992, which is a direct binding site for the PLC-gamma SH2 domain, and phosphotyrosine 1068, a binding site for the Grb2/SH2 domain. The expression of EGF-R and phosphorylated EGF-R will be determined in tumors as well as adjacent and remote normal appearing urothelium.

SECONDARY OBJECTIVES:

  1. Measuring tissue intermediate endpoint biomarkers such as EGF-R mutations (EGFR vIII, exon 19-21), Ki67, activated Caspase 3, Akt, P-Akt, MAP kinase, P-MAP kinase, COX-2, survivin, and BLCA-4 and we will also determine survivin and BLCA-4 levels in urine specimens as surrogate tumor markers. Biomarkers associated with the EGF-R pathway, including Akt and P-Akt will be studied by immunohistochemistry. Additionally, Ki67, activated Caspase 3 (as a marker of apoptosis), and COX-2 will serve as biological endpoint biomarkers to measure the effects of G-2535 on proliferation, apoptosis, and other processes and molecules relevant to bladder cancer. These studies will be performed on tumors as well as adjacent and remote normal urothelium. II. Safety will also be studied.

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.

Being tested
Genistein, Laboratory Biomarker Analysis, Pharmacological Study, Placebo Administration, Therapeutic Conventional Surgery
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GenisteinDrug

    Also called 4'',5, 7-Trihydroxyisoflavone, Genestein, Genisteol, Prunetol

    Given orally

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Placebo AdministrationOther

    Given orally

  • Therapeutic Conventional SurgeryProcedure or surgery

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

Study groups in NCT00118040
Study groupRoleWhat they receive
Arm I (lower dose genistein)ExperimentalPatients 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.
Receives: Drug: Genistein; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery
Arm II (higher dose genistein)ExperimentalPatients 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.
Receives: Drug: Genistein; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery
Arm III (placebo)Placebo comparatorPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo Administration; Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to 21 days

  2. 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.

    Measured: up to 21 days on Study Drug

Secondary outcomes (12)

  1. BLCA-4 in Urine by Visit

    Detecting the mean amount of the biomarker BLCA-4 in the urine of patients prior to starting study agent, at Day 8 and pre-surgery time (when they have been on study agent between 14-21 days). This is measured by urine analysis at each of the time points to serve as a surrogate tumor marker.

    Measured: up to 21 days

  2. Survivin in Urine by Visit (pg/ml)

    Detecting the mean amount of the biomarker Survivin in the urine of patients prior to starting study agent, at Day 8 and pre-surgery time (when they have been on study agent between 14-21 days). This is measured by urine analysis at each of the time points to serve as a surrogate tumor marker.

    Measured: up to 21 days

  3. Survivin in Tumor Tissue

    Detecting the signal of the biomarker, Survivin, in the tumor 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.

    Measured: up to 21 days on Study Drug

  4. EGFR Mutations in Tumor Tissue

    Detecting the signal of EGFR mutations in the tumor 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.

    Measured: up to 21 days on Study Drug

  5. EGFR in Benign Tissue

    Detecting the signal of the biomarker, EGFR, 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.

    Measured: up to 21 days on Study Drug

  6. Ki-67 in Tumor Tissue

    Detecting the signal of the biomarker, Ki-67, in the tumor tissue after being on study drug for between 14-21 days as a way to measuring the effects G-2535 have on it with regards to proliferation, apoptosis, and other processes relevant to bladder cancer.

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

    Measured: up to 21 days on Study Drug

  7. Activated Caspase 3 in Tumor Tissue

    Detecting the signal of the biomarker, Activated Caspase 3, in the tumor tissue after being on study drug for between 14-21 days as a way to measuring the effects G-2535 have on it with regards to proliferation, apoptosis, and other processes relevant to bladder cancer.

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

    Measured: up to 21 days on Study Drug

  8. COX2 in Tumor Tissue

    Detecting the signal of the biomarker, COX2, in the tumor tissue after being on study drug for between 14-21 days as a way to measuring the effects G-2535 have on it with regards to proliferation, apoptosis, and other processes relevant to bladder cancer.

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

    Measured: up to 21 days on Study Drug

  9. AKT in Tumor Tissue

    Detecting the signal of the biomarker, AKT, in the tumor 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.

    Measured: up to 21 days on Study Drug

  10. pAKT in Tumor Tissue

    Detecting the signal of the biomarker, pAKT, in the tumor 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.

    Measured: up to 21 days on Study Drug

  11. MAP Kinase in Tumor Tissue

    Detecting the signal of the biomarker, MAP Kinase, in the tumor 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.

    Measured: up to 21 days on Study Drug

  12. pMAP Kinase in Tumor Tissue

    Detecting the signal of the biomarker, pMAP Kinase, in the tumor 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.

    Measured: up to 21 days on Study Drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2005 (estimated)
  2. Study start24 Jun 2005
  3. Primary completion15 Aug 2010
  4. Study completion15 Aug 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00118040
Sponsor's protocol ID
NCI-2013-00453
Other IDs
NCI-2013-00453, CDR0000433520, WCCC-UWI03-1-01, WCCC-CO-04307, UWI03-1-01, UWI03-1-01, N01CN35153
Status last verified
Mar 2021
First submitted
8 Jul 2005
Last updated
10 Jun 2021

Publications

  • 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.

    PubMed 22293631

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Genistein, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Bladder Carcinoma and Stage I Bladder Cancer AJCC v6 and v7, run by National Cancer Institute (NCI) at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Epidermal Growth Factor Receptor (EGFR) Phosphorylation in Tumor Tissue, as Measured by Immunohistochemistry After the Completion of Treatment (time frame: up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00118040, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.

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