A Randomized Trial of Bicalutamide in Non-Muscle Invasive Bladder Cancer

This phase I trial evaluates the effects of bicalutamide, compared to no study drug (NSD), on epidermal growth factor receptor (EGFR) protein expression in patients with non-muscle invasive bladder cancer. Bicalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Previous studies have suggested that expression of a protein called EGFR on tumor cells is related to bladder cancer disease progression. This trial may help doctors evaluate if bicalutamide has any effect on EGFR expression in patients with non-muscle invasive bladder cancer.

Study Overview

• Status: Recruiting
• Conditions: Non-Muscle Invasive Bladder Urothelial Carcinoma; Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Bicalutamide; Procedure: Transurethral Resection of Bladder Tumor

Detailed Description

PRIMARY OBJECTIVE:

1. To compare epidermal growth factor receptor (EGFR) messenger ribonucleic acid (mRNA) expression measured by reverse transcriptase polymerase chain reaction (rt-PCR) in normal appearing urothelium adjacent to tumor (measured as a ratio relative to urothelium and lamina-propria specific markers) in participants treated with anti-androgen therapy versus (vs.) participants given NSD.

SECONDARY OBJECTIVES:

1. To determine effect of bicalutamide on EGFR expression (by rtPCR) in the subgroup of patients whose normal appearing urothelium adjacent to tumor expresses the androgen receptor (AR) (at least "1" by immunohistochemistry [IHC] score).
2. To correlate AR expression in adjacent urothelium (by IHC score) with EGFR expression by rtPCR in participants randomized to bicalutamide versus NSD.
3. Comparison of pre vs. post intervention urinary biomarkers (CxBladderTM) in both groups, examining the 5 RNAs (by RT-PCR) that make up the test, both as a group and each RNA separately.

EXPLORATORY OBJECTIVES:

1. Comparison of AR and EGFR (and possibly phosphorylated EGFR [pEGFR]) staining levels (low, moderate, high; by immunocytology) in pre-treatment vs. post-treatment bladder wash immunocytology.
2. To compare expression of direct androgen response gene (ADAR)-2 measured by rtPCR in normal appearing adjacent (to tumor) urothelium that does and does not express AR (by IHC), in participants randomized to bicalutamide versus NSD.
3. Ki-67 expression (by IHC) in normal appearing urothelium adjacent to tumor in participants randomized to bicalutamide versus NSD.
4. Subgroup analysis of Ki-67 expression in the AR+ subgroup.
5. Differences in expression of AR, EGFR, pEGFR, and Ki-67 (by semi-quantitative IHC) in tumor in participants randomized to bicalutamide versus NSD.
6. Change in EGFR expression by rt-PCR in tumor in participants randomized to bicalutamide versus NSD.
7. Fibroblast growth factor receptor 3 (FGFR3) mutation analysis in deoxyribonucleic acid (DNA) extracted from formalin fixed paraffin embedded (FFPE) blocks from neighboring normal urothelium and tumor tissue in participants randomized to bicalutamide versus NSD.
8. Define changes in the tumor immune microenvironment pre- and post-bicalutamide through liquid biopsies of blood and urine using high-dimensional flow cytometry.
9. Analyze tumor (biopsy specimen) immune microenvironment via multiplex immunofluorescence and spatial transcriptomics.
10. Other exploratory markers such as changes in the urinary microbiome in bladder cancer participants randomized to bicalutamide versus NSD.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive bicalutamide orally (PO) once daily (QD) on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of bicalutamide prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.

ARM 2: Patients receive NSD PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of NSD prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.

After completion of study treatment, patients are followed up 20-30 days after TURBT.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Recruiting
      • University of Arizona Cancer Center - Prevention Research Clinic
      • Contact: Juan Chipollini; Phone Number: 520-694-4032; Email: jchipollini@surgery.arizona.edu
      • Principal Investigator: Juan Chipollini
  • California
    • Los Angeles, California, United States, 90048
      • Not yet recruiting
      • Cedars Sinai Medical Center
      • Contact: Michael A. Ahdoot; Phone Number: 310-423-2659; Email: Michael.Ahdoot@cshs.org
      • Principal Investigator: Michael A. Ahdoot
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Not yet recruiting
      • National Cancer Institute Urologic Oncology Branch
      • Contact: Sandeep Gurram; Phone Number: 240-858-3700; Email: Sandeep.Gurram@nih.gov
      • Principal Investigator: Sandeep Gurram
  • New York
    • Rochester, New York, United States, 14642
      • Not yet recruiting
      • University of Rochester
      • Contact: Edward M. Messing; Phone Number: 585-275-3345; Email: edward_messing@urmc.rochester.edu
      • Principal Investigator: Edward M. Messing
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Contact: Debasish Sundi; Phone Number: 219-713-9783; Email: D.Sundi@osumc.edu
      • Principal Investigator: Debasish Sundi
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Carbone Cancer Center - University Hospital
      • Contact: Kyle A. Richards; Phone Number: 608-262-0759; Email: richardsk@urology.wisc.edu
      • Principal Investigator: Kyle A. Richards

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Biologic male adults (>= 18 years old)

  • Note: Because no dosing or adverse event (AE) data are currently available on the use of bicalutamide in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable

• Have suspected new or occasionally recurrent NMIBC (i.e., </= 2 prior NMIBC episodes in the 18 months preceding the cystoscopy where the index tumor was identified) on clinic-based cystoscopy or imaging as viewed by an American Urological Association (AUA) board-certified urologist

• Have had cross sectional imaging of the abdomen and pelvis (computed tomography [CT] or magnetic resonance imaging [MRI] with or without contrast) within 6 months prior to enrollment with no signs of upper tract urothelial cancer (UC), invasive, nor metastatic disease

  • Note: If adenopathy or upper tract abnormalities are identified, a negative biopsy and or ureteroscopy is required prior to enrollment

• Participants with single and multiple tumor lesions

• In the opinion of the treating urologist, the participant is suitable to undergo surgery.

• Participants may have received intravesical chemotherapy at any time.

• Total bilirubin =< 1.5 x institutional upper limit of normal (note: in participants with Gilbert's syndrome, if total bilirubin is > 1.5 x upper limit of normal, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x upper limit of normal, participants may be eligible)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2 × institutional upper limit of normal

• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 × institutional upper limit of normal

• Serum Testosterone >= 250 ng/dL

• Thyroid stimulating hormone (TSH) within institutional normal

• The effects of bicalutamide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, men who are having sex must wear a condom when engaging in any activity that allows for passage of ejaculate to another person throughout the course of the study and 4 months after receiving last dose of study intervention. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak. Additionally, men must agree to not donate sperm for the purpose of reproduction during the study and for a minimum of 4 months after receiving the last dose of study intervention

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants who have had a previous exposure to sex hormone (e.g., exogenous androgens) or anti-androgenic therapies (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, 5 alpha reductase-inhibitors, abiraterone or other anti-androgens) within 6 months of accrual
• Participants taking Coumarin derivative anticoagulation (e.g., warfarin). Other anticoagulation medications are allowed.
• Participants receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bicalutamide.
• History of prior or concurrent muscle invading UC, or concurrent prostatic urethral, urethral, or upper tract UC or non-urothelial bladder cancer
• History of radiation therapy to the pelvis, prostate or prostatic bed, or rectum
• Any condition (uncontrolled intercurrent illness, psychiatric illness, or social situation) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Allergy or hypersensitivity to bicalutamide, or excipients, unable or unwilling to take ADT.
• Plans to father a child while enrolled in this study or within 4 months after the last dose of study intervention.
• Participants with suspected Carcinoma in Situ (CIS) without suspected Ta or T1 disease are not eligible.
• Participants with a history of documented CIS within 2 years are not eligible.
• Participants who have received Gacillus Calmette-Guerin (BCG) within 2 years are not eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 (bicalutamide,TURBT); Patients receive bicalutamide PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of bicalutamide prior to TURBT is permitted in the absence of unacceptable toxicity. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biopsy Procedure; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy; Procedure: Biospecimen Collection; Undergo blood and urine sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Bicalutamide; Given PO; Other Names: Casodex; Procedure: Transurethral Resection of Bladder Tumor; Undergo TURBT; Other Names: Transurethral resection (TURBT); TURBT
Experimental: Arm 2 (TURBT); Patients undergo TURBT on day 21. Patients undergo blood and urine sample collection throughout the study. Patients may optionally undergo tumor biopsy at baseline.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biopsy Procedure; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy; Procedure: Biospecimen Collection; Undergo blood and urine sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Transurethral Resection of Bladder Tumor; Undergo TURBT; Other Names: Transurethral resection (TURBT); TURBT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Epidermal Growth Factor Receptor (EGFR) expression level	Will be analyzed as a continuous variable. A two-sample t-test will be conducted to test whether there are significant differences of the log-transformed EGFR expression level (measured by reverse transcriptase polymerase chain reaction [rtPCR]) in normal appearing urothelium adjacent to tumor in participants treated with anti-androgen therapy versus (vs.) NSD participants. In case the normality assumption of the two-sample t-test does not hold, Wilcoxon rank-sum test will be performed as a sensitivity analysis. Considering androgen receptor (AR) status can be a treatment effect modifier, a regression analysis will also be performed with the log-transformed EGFR expression level as the outcome and treatment status (bicalutamide or NSD), AR status, and treatment-AR interaction as the predictors.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of bicalutamide on EGFR expression	A two-sample Wilcoxon rank-sum test will be conducted to compare the difference of EGFR expression in AR positive participants treated with and without bicalutamide.	Up to 28 days
AR expression in adjacent urothelium	Will evaluate the correlation between AR expression in adjacent urothelium with EGFR expression. Pearson correlation and Spearman's rank correlation will be calculated between the AR expression and EGFR expression.	Up to 28 days
Pre vs. post intervention urinary biomarkers	Comparison of pre vs. post intervention urinary biomarkers (CxBladderTM) in both groups, examining the 5 ribonucleic acids (RNAs) (by rtPCR) that make up the test, both as a group and each RNA separately. Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AR and EGFR (and possibly phosphorylated EGFR [pEGFR]) staining levels	Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
Expression of direct androgen response gene (ADAR)-2	Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
Ki-67 expression	Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
Ki-67 expression in the AR+ subgroup	Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
Differences in expression of AR, EGFR, pEGFR, and Ki-67	Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
Change in EGFR expression in tumor from participants randomized to bicalutamide versus NSD	Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
Analysis of fibroblast growth factor receptor 3 (FGFR3) in deoxyribonucleic acid (DNA)	Extracted from fixed paraffin embedded (FFPE) blocks from neighboring normal urothelium and tumor tissue in participants treated with or without bicalutamide. Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
Changes in the tumor immune microenvironment pre- and post-bicalutamide	Will be summarized by descriptive statistics such as rates and proportions.	Up to 28 days
Analysis of tumor (biopsy specimen) infiltrating CD8+ T-cells	The tumor immune microenvironment will be analyzed via multiplex immunofluorescence and spatial transcriptomics. Assessments will include CD8+ T-cell functional markers: TCF1/Tcf7 of CD44+, CD62L, PD-1, TIM3 and SLAMF6. Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days
AR, EGFR, and pEGFR in biopsies of tumors	Optional biopsy tissue will be used to compare AR, EGFR, and pEGFR in biopsies of tumors done at index cystoscopy vs. transurethral resection of bladder tumor in participants randomized to bicalutamide versus NSD.	At index cystoscopy and TURBT
Exploratory markers	Will be summarized by descriptive statistics such as rates and proportions and compared between NSD and bicalutamide using nonparametric tests such as the Kruskal-Wallis test.	Up to 28 days

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Edward M Messing, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 27, 2022
• First Submitted That Met QC Criteria: August 27, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 25, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Urologic Surgical Procedures; Urogenital Surgical Procedures; Biopsy; Specimen Handling; Transurethral Resection of Bladder; bicalutamide
• Other Study ID Numbers: 2026-0131; P30CA014520 (U.S. NIH Grant/Contract); UG1CA242635 (U.S. NIH Grant/Contract); NCI-2022-06871 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); INT22-09-01 (Other Identifier: DCP); 2026-0131 (Other Identifier: UWCCC); Protocol Version 8/26/26 (Other Identifier: DCP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No