NIPH Clinical Trials Search

Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Non-Muscle-Invasive Bladder Cancer (NIMBC) Muscle-Invasive Bladder Cancer (MIBC)
Date of first enrollment	01/08/2025
Target sample size	262
Countries of recruitment	Canada,Japan,Germany,Japan,Israel,Japan,Korea Republic Of,Japan,Netherlands Kingdom Of The,Japan,Spain,Japan,United States Of America,Japan
Study type	Interventional
Intervention(s)	Experimental: Part 1: Dose Escalation Participants with recurrent, bacillus Calmette-Guerin (BCG)-experienced high risk papillary-only Non-Muscle-Invasive Bladder Cancer (NMIBC), refusing or ineligible for radical cystectomy or with recurrent, intermediate-risk NMIBC will receive Erdafitinib Intravesical Delivery System. The dose will be escalated to determine preliminary recommended phase 2 dose(s) (RP2D[s]) for Part 2. Drug: Erdafitinib Intravesical Delivery System Erdafitinib intravesical delivery system will be administered. Other Names: JNJ-42756493 Experimental: Part 2: Dose Expansion Participants in each of 5 disease-specific NMIBC or MIBC cohorts may be enrolled at one or more dose levels that have been determined to be safe in Part 1. Drug: Erdafitinib Intravesical Delivery System Erdafitinib intravesical delivery system will be administered. Other Names: JNJ-42756493 Experimental: Part 3: RP2D Dose Expansion Participants in 2 of the disease-specific NMIBC cohorts (cohorts 1 and 3) may be enrolled at RP2D to determine the safety, evaluate PK and preliminary clinical activity. Drug: Erdafitinib Intravesical Delivery System Erdafitinib intravesical delivery system will be administered. Other Names: JNJ-42756493 Experimental: Part 4: Phase 2 Expansion Participants with recurrent IR-NMIBC will be enrolled in this part to further evaluate the safety, efficacy, and PK of the selected RP2D. Drug: Erdafitinib Intravesical Delivery System Erdafitinib intravesical delivery system will be administered. Other Names: JNJ-42756493

Outcome(s)

Primary Outcome

1. Parts 1 to 3: Number of Participants with Adverse Events (AEs) An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. [Time Frame: Up to 5 years 11 months] 2. Parts 1 to 3: Number of Participants with AEs by Severity Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. [Time Frame: Up to 5 years 11 months] 3. Part 1: Number of Participants with Dose-limiting Toxicity (DLT) Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. [Time Frame: Up to 28 days] 4. Part 4: Overall Complete Response (CR) in Participants with Intermediate Risk-Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Overall CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy. [Time Frame: Up to 5 years 11 months]

Secondary Outcome

5. Parts 1 to 3: Plasma Concentration of Erdafitinib Plasma concentration of Erdafitinib will be reported. [Time Frame: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks] 6. Parts 1 to 3: Urine Concentration of Erdafitinib Urine concentration of Erdafitinib will be reported. [Time Frame: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks] 7. Parts 1 to 3: Cohorts 1 and 2: Recurrence-Free Survival (RFS) RFS is defined as the time from start of treatment to the first detection of any new high-grade bladder cancer or upper tract urothelial carcinoma or positive urine cytology. [Time Frame: Up to 5 years 11 months] 8. Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate CR is defined as the absence of urothelial carcinoma by cystoscopy, confirmed pathologically at first assessment, and negative urine cytology. [Time Frame: At 3 months] 9. Parts 1 to 3: Cohort 3 and 5: Duration of CR Duration of CR is defined as the time from first documentation of CR until the date of documented recurrence or progression, or death, whichever comes first. [Time Frame: Up to 5 years 11 months] 10. Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate pCR rate is defined as percentage of participants with no pathologic evidence of intravesical disease (pT0) and no pathologic evidence of nodal involvement (pN0). [Time Frame: Up to 8 weeks] 11. Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0) pT0 rate is defined as percentage of participants with no Pathologic Evidence of Intravesical Disease. [Time Frame: Up to 8 weeks] 12. Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2 Rate of downstaging to <pT2 is defined as percentage of participants with pT stage <2. [Time Frame: Up to 8 weeks] 13. Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC Duration of CR is defined as the time from first documentation of CR until the date of documented recurrence or progression, or death, whichever comes first. [Time Frame: Up to 5 years 11 months] 14. Part 4: Complete Response (CR) in Participants with IR-NMIBC CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy at the first disease evaluation. [Time Frame: At Month 3] 15. Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC Participants with TURBT-free survival will be reported. [Time Frame: Up to 5 years 11 months] 16. Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that has worsened since baseline. Severity was assessed using National cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0. Severity grades ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. [Time Frame: Up to 5 years 11 months] 17. Part 4: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 ""Not at all"" to 4 ""Very much."" Two global health status items are rated on a 7-point numeric rating scale from 1 ""Very Poor"" to 7 ""Excellent."" Higher scores indicate greater functioning, better global health status, and more severe symptoms. [Time Frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at the End of Treatment (EOT; that is Week 49)] 18. Part 4: Change from Baseline in European Organization for the Research and Treatment of Cancer Non-Muscle Invasive Bladder Cancer (EORTC-QLQ-NMIBC 24) Score EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with non-muscle-invasive bladder cancer. The questionnaire is designed to supplement the QLQ C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much). Higher scores indicated greater severity. [Time Frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at the EOT (that is Week 49)] 19. Part 4: Percentage of Participants With Clinically Meaningful Change From Baseline in EORTC-QLQ-C30 Scores The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status/quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 ""Not at all"" to 4 ""Very much."" Two global health status items are rated on a 7-point numeric rating scale from 1 ""Very Poor"" to 7 ""Excellent."" Higher scores indicate greater functioning, better global health status, and more severe symptoms. [Time Frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at the EOT (that is Week 49)] 20. Part 4: Percentage of Participants With Clinically Meaningful Change From Baseline in EORTC-QLQ-NMIBC24 Scores EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with non-muscle-invasive bladder cancer. The questionnaire is designed to supplement the QLQ C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much). Higher scores indicated greater severity. [Time Frame: At baseline (Week 0), Weeks 12, 24, 36, 48, and at the EOT (that is Week 49)]

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	Parts 1-3: - Muscle-invasive or recurrent, non-muscle-invasive urothelial carcinoma of the bladder - For selected Cohorts: Activating tumor pan-fibroblast growth factor receptor (FGFR) mutation or fusion, as determined by local or central testing, approved by the sponsor prior to the start of study treatment. Local tissue-based results (if already existing) from next-generation sequencing (NGS) or polymerase chain reaction (PCR) tests performed in Clinical Laboratory Improvement Amendments (CLIA) -certified or equivalent laboratories, or results from commercially available PCR or NGS tests - Cohorts 1 and 2: Bacillus Calmette-Guerin (BCG) experienced, or participants with no BCG experience because BCG was not available as a treatment option in the participant's location within the previous 2 years and is currently unavailable. Participants who received an abbreviated course of BCG due to toxicity are still eligible - Cohort 1 only: Refuses or is not eligible for radical cystectomy (RC) - Cohorts 2 and 4: Willing and eligible for RC Part 4: - Have histologically confirmed diagnosis of recurrent Intermediate-risk-nonmuscle invasive bladder cancer (IR-NMIBC) Ta LG tumors - Must not have undergone tumor debulking or selective ablation of visible lesions; partial tumor biopsy to confirm diagnosis and provide tissue for biomarker testing is permitted as long as remaining tumor is at least 5 millimeter (mm) in size - Must submit tissue and urine for FGFR testing - Can have a prior or concurrent second malignancy which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment
Exclude criteria	Parts 1-3: - Concurrent extra-vesical (that is, urethra, ureter, renal pelvis) transitional cell carcinoma of the urothelium - Prior treatment with an pan-fibroblast growth factor receptor (FGFR) inhibitor - Received pelvic radiotherapy <=6 months prior to the planned start of study treatment. If received pelvic radiotherapy greater than (>)6 months prior to the start of study treatment, there must be no cystoscopic evidence of radiation cystitis - Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe use of Erdafitinib intravesical delivery system - Indwelling urinary catheter. Intermittent catheterization is acceptable Part 4: - Histologically confirmed diagnosis of T1 NMIBC, HR NMIBC (HG/G2 or HG/G3 or CIS) or MIBC, locally advanced, non-resectable, or metastatic urothelial carcinoma at any time prior to enrollment - Known allergies, hypersensitivity, or intolerance to any study component or its excipients - Has a current diagnosis of primary IR-NMIBC - Received an investigational treatment for bladder cancer after Transurethral Resection of the Bladder Tumor (TURBT) for the current NMIBC diagnosis or within 4 weeks or the agent/therapy washout period, whichever is longer, before the planned first dose of study treatment, or is currently enrolled in an investigational study - Evidence of current bladder perforation by cystoscopy or imaging