NCT05521698

Study to Determine Possible Effects of Apalutamide, Compared to Placebo, on EGFR Expression in Patients With Non-muscle Invasive Bladder Cancer

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

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial evaluates the effects of apalutamide, compared to placebo, on epidermal growth factor receptor (EGFR) protein expression 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 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.

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 placebo. SECONDARY OBJECTIVES: I. To determine effect of apalutamide 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 apalutamide versus placebo. III. Comparison of toxicity in participants randomized to apalutamide versus placebo. 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 apalutamide versus placebo. III. Ki-67 expression (by IHC) in normal appearing urothelium adjacent to tumor in participants randomized to apalutamide versus placebo. 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 apalutamide versus placebo. VI. Comparison of demographics of two groups. VII. Change in EGFR expression by rt-PCR in tumor in participants randomized to apalutamide versus placebo. 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 apalutamide versus placebo. XI. Define changes in the tumor immune microenvironment pre- and post-apalutamide 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 apalutamide versus placebo. (Optional) XIV. Other exploratory markers such as changes in the urinary microbiome in bladder cancer participants randomized to apalutamide versus placebo. 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 apalutamide 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 placebo PO QD on days 1-21. Patients undergo TURBT on day 21. Up to 28 days of placebo 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.

Conditions

• Non-Muscle Invasive Bladder Urothelial Carcinoma
• Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Apalutamide	Given PO
PROCEDURE	Biopsy Procedure	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood and urine sample collection
DRUG	Placebo Administration	Given PO
OTHER	Questionnaire Administration	Ancillary studies
PROCEDURE	Transurethral Resection of Bladder Tumor	Undergo TURBT

Timeline

• Start date: 2026-04-01
• Primary completion: 2028-06-01
• Completion: 2028-12-01
• First posted: 2022-08-30
• Last updated: 2026-02-17

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study