NCT04172675.

Study name	A study of erdafitinib versus investigator choice of intravesical chemotherapy in participants who received Bacillus Calmette‐Guérin (BCG) and recurred with high risk non‐muscle‐invasive bladder cancer (NMIBC)
Methods	Open‐label, parallel, randomized study
Participants	Estimated enrollment: 280 participants Eligible ages: > 18 years Eligible sexes: both Eligibility criteria Inclusion criteria Histologically confirmed, recurrent, non‐muscle‐invasive urothelial carcinoma of the bladder. Variant pathologies are allowed Tumor with specified fibroblast growth factor receptor mutations or fusions BCG‐unresponsive after adequate BCG therapy or BCG experienced participants Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only) ECOG performance status Grade 0–1 Must sign an informed consent form (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study A woman of childbearing potential must have a negative pregnancy test (beta‐human chorionic gonadotropin) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3) Adequate bone marrow, liver, and renal function as specified in the protocol Exclusion criteria Histologically confirmed, muscle‐invasive (≥ T2 stage) urothelial carcinoma of the bladder Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder Prior treatment with a fibroblast growth factor receptor inhibitor Active malignancies other than the disease being treated under study. The only allowed exceptions are: skin cancer treated within the last 24 months that is considered completely cured; adequately treated lobular CIS and ductal CIS; history of localized breast cancer and receiving antihormonal agents; or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy Current central serous retinopathy or retinal pigment epithelial detachment of any grade
Interventions	Intervention: cohort 1, 2, and 3 will receive erdafitinib; orally beginning on cycle 1 day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is 28 days. Cohort 1: participants with high‐risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy Cohort 2: participants with high‐risk, BCG‐unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor Cohort 3: marker lesion study in intermediate‐risk NMIBC presenting as papillary disease only. Comparator: cohort 1 will receive investigators choice of intravesical chemotherapy; gemcitabine or mitomycin C Cohort 1: participants with high‐risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy will receive the investigator's choice of either intravesical gemcitabine or intravesical mitomycin C/hyperthermic mitomycin C. Participants who are randomized to gemcitabine or mitomycin C/hyperthermic mitomycin C in cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib.
Outcomes	Primary outcomes Recurrence‐free survival up to 4 years Secondary outcomes Time to progression up to 4 years Time to disease worsening up to 4 years Disease‐specific survival up to 4 years Overall survival up to 4 years Recurrence‐free survival at month 6, month 12, and month 24 Recurrence‐free survival 2 up to 4 years Recurrence‐free survival by central histopathologic review up to 4 years Plasma concentration of erdafitinib cycle 1 day 14, cycle 2 day 1 (each cycle is 28 days) Number of participants with adverse events up to 4 years Change from baseline in Patient's Global Impression of Severity (of cancer) (PGIS) to 4 years Change from baseline in Patient's Global Impression of Change (of cancer) (PGIC) to cycle 2 Day 1 and end of treatment (up to 2 years) (each cycle is 28 days) Change from baseline in European Organisation for Research and Treatment of Cancer Quality‐of‐life Questionnaire (EORTC QLQ) – C30 to 4 years Change from baseline in EORTC QLQ – NMIBC24 to 4 years Change from baseline in EuroQol European Quality of Life – 5 Dimensions‐5 Levels (EQ‐5D‐5L) to 4 years Maximum observed analyte concentration (Cmax) of midazolam and its metabolite (1‐OH‐midazolam) at predose and cycle 1 day 13 (each cycle is 28 days) Time to reach maximum observed analyte concentration (Tmax) midazolam and its metabolite (1‐OH‐midazolam) at predose and cycle 1 day 13 (each cycle is 28 days) Area under the analyte concentration vs time curve (AUC) from time zero to the time of last measurable analyte concentration of midazolam and its metabolite (1‐OH‐midazolam) at predose and cycle 1 day 13 (each cycle is 28 days) Area under the analyte concentration vs time curve (AUC) from time zero to infinite time of midazolam and its metabolite (1‐OH‐midazolam) at predose and cycle 1 day 13 (each cycle is 28 days) Maximum observed plasma concentration (Cmax) of metformin at predose and cycle 1 day 14 (each cycle is 28 days) Time to reach maximum observed plasma concentration (Tmax) of metformin at predose and cycle 1 day 14 (each cycle is 28 days) Area under the analyte concentration vs time curve (AUC) from time zero to the time of last measurable of metformin at predose and cycle 1 day 14 (each cycle is 28 days) Area under the analyte concentration vs time curve (AUC) from time zero to infinite time of metformin at predose and cycle 1 day 14 (each cycle is 28 days)
Starting date	February 28, 2020 Expected date of completion: 10 June 2026
Contact information	Tel: +1 844‐434‐4210; email: JNJ.CT@sylogent.com
Notes	Funding source: Janssen Research & Development, LLC Sponsors and Collaborators: Janssen Research & Development, LLC

BCG: Bacillus Calmette‐Guérin; CIS: carcinoma in situ; CT: computer tomography; CTCAE: Common Terminology Criteria for Adverse Events; ECOG: Eastern Cooperative Oncology Group; G: tumor grade; NCI: National Cancer Institute; NMIBC: non‐muscle invasive bladder cancer; TUR: transurethral resection; TURBT: transurethral resection of the bladder tumor.