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

Summary

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.

Detailed description

PRIMARY OBJECTIVE: I. 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: I. 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). II. To correlate AR expression in adjacent urothelium (by IHC score) with EGFR expression by rtPCR in participants randomized to bicalutamide versus NSD. III. Comparison of toxicity in participants randomized to bicalutamide versus NSD. EXPLORATORY OBJECTIVES: I. 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 cytology. II. 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. III. Ki-67 expression (by IHC) in normal appearing urothelium adjacent to tumor in participants randomized to bicalutamide versus NSD. IV. Subgroup analysis of Ki-67 expression in the AR+ subgroup. V. Differences in expression of AR, EGFR, pEGFR, and Ki-67 (by semi-quantitative IHC) in tumor in participants randomized to bicalutamide versus NSD. VI. Comparison of demographics of two groups. VII. Change in EGFR expression by rt-PCR in tumor in participants randomized to bicalutamide versus NSD. VIII. Morbidities of treatment (breast tenderness, sexual or urinary side effects, seizure\[s\], depression, abnormal liver function tests \[LFTs\]). IX. Comparison of pre vs. post intervention urinary biomarkers (CxBladderTM) in both groups, examining the 5 RNAs (by rtPCR) that make up the test, both as a group and each RNA separately. X. 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. XI. Define changes in the tumor immune microenvironment pre- and post-bicalutamide through liquid biopsies of blood and urine using high-dimensional flow cytometry. XII. Analyze tumor (biopsy specimen) immune microenvironment via multiplex immunofluorescence and spatial transcriptomics. XIII. Compare AR, EGFR, and pEGFR in biopsies of tumors done at index cystoscopy vs. TURBT in participants randomized to bicalutamide versus NSD. (Optional) XIV. 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.

Arms & interventions

• DrugBicalutamide

  Given PO

• ProcedureBiopsy Procedure

  Undergo tumor biopsy

• ProcedureBiospecimen Collection

  Undergo blood and urine sample collection

• OtherQuestionnaire Administration

  Ancillary studies

• ProcedureTransurethral Resection of Bladder Tumor

  Undergo TURBT

Outcome measures

Eligibility criteria