Non-Muscle-Invasive Bladder Cancer (NMIBC) Muscle-Invasive Bladder Cancer (MIBC)
Conditions
Interventions
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 ineligibl
Sponsors
Ote Tatsuya
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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
Exclusion criteria
Exclusion 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 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.Previous high grade (HG) disease is accepted as long as diagnosis date is greater than or equal to (>=5) years ago and there is documentation of low grade (LG) Ta thereafter. - Known allergies, hypersensitivity, or intolerance to any study component or its excipients - Has a current diagnosis of newly diagnosed 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 approximately 7 years 4 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 approximately 7 years 4 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 approximately 7 years 4 months] | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 approximately 7 years 4 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 approximately 7 years 4 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 progressi | — |
Countries
Canada, Germany, Israel, Japan, Korea Republic Of, Netherlands Kingdom Of The, Spain, United States Of America
Contacts
Public ContactMedical Information Center
Janssen Pharmaceutical K.K.
Outcome results
None listed