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.
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
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.
Parallel
Bicalutamide
DrugGiven PO
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood and urine sample collection
Questionnaire Administration
Other interventionAncillary studies
Transurethral Resection of Bladder Tumor
Procedure/SurgeryUndergo TURBT
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.
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.
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.
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.
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.
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.
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.
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.
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University of Wisconsin, Madison
Lead sponsor
National Cancer Institute (NCI)
Collaborator
