Non-Muscle Invasive Bladder Urothelial Carcinoma Clinical Trial
Official title:
A Randomized Trial of Apalutamide in Non-Muscle Invasive Bladder Cancer
This randomized trial investigates the possible effect of apalutamide in patients with non-muscle invasive bladder cancer. Apalutamide 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 epidermal growth factor receptor (EGFR) on tumor cells is related to bladder cancer disease progression. This trial may help doctors evaluate if apalutamide has any effect on EGFR expression in patients with non-muscle invasive bladder cancer.
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 apalutamide therapy versus (vs.) untreated participants. SECONDARY OBJECTIVES: I. To determine the possible effect of apalutamide on EGFR expression (by rtPCR) in the subgroup of patients whose normal appearing urothelium adjacent to tumor expresses the 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 treated and untreated participants. III. Comparison of toxicity of treatment group to untreated control. 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 apalutamide treated participants and untreated controls. III. Ki-67 expression (by IHC) in normal appearing urothelium adjacent to tumor in treated vs. untreated participants. 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 treated vs untreated participants. VI. Comparison of demographics of two groups. VII. Change in EGFR expression by rt-PCR in tumor from treated vs. untreated participants. 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 treated vs. untreated participants. XI. Define changes in the tumor immune microenvironment pre- and post-apalutamide through liquid biopsies of blood and urine using high-dimensional flow cytometry and single cell transcriptomics. XII. Analyze tumor (biopsy specimen) infiltrating CD8+ T-cells by single RNA Sequencing (scRNA-seq) and high dimensional spectral flow cytometry to evaluate TCF1/Tcf7 transcript levels, and perform IHC of CD44+, CD62L, and SLAMF6. XIII. Other exploratory markers. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive apalutamide orally (PO) once daily (QD) on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of treatment is permitted in the absence of unacceptable toxicity. Patients undergo blood specimen collection at baseline and at time of TURBT. ARM 2: Patients undergo TURBT on day 21. Patients undergo blood specimen collection at baseline and at time of TURBT. After completion of study treatment, patients are followed up 20-30 days after TURBT. ;
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