Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer
- Conditions
- Urinary Bladder NeoplasmsReceptors, Fibroblast Growth Factor
- Interventions
- Registration Number
- NCT05316155
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of the study in Part 1 (dose escalation) and in Part 2 (dose expansion) is to determine the recommended Phase 2 dose(s) (RP2D\[s\]) and evaluate preliminary clinical efficacy. Part 3 (dose expansion) will confirm safety and preliminary clinical activity at the RP2D. Part 4 (RP2D expansion) will assess the overall complete response (CR) in participants with intermediate-risk-non-muscle invasive bladder cancer (IR-NMIBC; means the cancer cells are only in the bladder's inner lining).
- Detailed Description
Bladder cancer is one of the most common malignancy worldwide, and non-muscle invasive (NMIBC) requires intensive regimens of frequent monitoring and local resection (transurethral resection of bladder \[TURBT\]). This study enrolls participants with non-muscle invasive or muscle invasive bladder cancer with activating fibroblast growth factor receptor (FGFR) mutations or fusions. Erdafitinib is a pan-FGFR inhibitor with demonstrated clinical activity when administered orally in patients with solid tumors, including bladder cancer, with FGFR genetic alterations. The Erdafitinib intravesical delivery system is designed to provide release of Erdafitinib in the bladder to treat localized bladder cancer, while reducing systemic toxicities. The study consists of a screening phase, a treatment phase, and a follow-up phase. Total duration of the study is 5 years 11 months.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 262
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-Guérin (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-non-muscle 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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2: Dose Expansion Erdafitinib Intravesical Delivery System 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. Part 3: RP2D Dose Expansion Erdafitinib Intravesical Delivery System 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. Part 1: Dose Escalation Erdafitinib Intravesical Delivery System 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. Part 4: Phase 2 Expansion Erdafitinib Intravesical Delivery System Participants with recurrent IR-NMIBC will be enrolled in this part to further evaluate the safety, efficacy, and PK of the selected RP2D.
- Primary Outcome Measures
Name Time Method Part 4: Overall Complete Response (CR) in Participants with Intermediate Risk-Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Up to 5 years 11 months Overall CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy.
Parts 1 to 3: Number of Participants with AEs by Severity Up to 5 years 11 months 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.
Parts 1 to 3: Number of Participants with Adverse Events (AEs) Up to 5 years 11 months 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.
Part 1: Number of Participants with Dose-limiting Toxicity (DLT) Up to 28 days 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.
- Secondary Outcome Measures
Name Time Method Parts 1 to 3: Cohorts 1 and 2: Recurrence-Free Survival (RFS) Up to 5 years 11 months 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.
Parts 1 to 3: Cohort 3 and 5: Duration of CR Up to 5 years 11 months 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.
Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC Up to 5 years 11 months Participants with TURBT-free survival will be reported.
Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2 Up to 8 weeks Rate of downstaging to \<pT2 is defined as percentage of participants with pT stage \<2.
Part 4: Percentage of Participants With Significant Change From Baseline in EORTC-QLQ-NMIBC24 Scores Up to 5 years 11 months 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.
Parts 1 to 3: Urine Concentration of Erdafitinib Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks Urine concentration of Erdafitinib will be reported.
Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC Up to 5 years 11 months 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.
Parts 1 to 3: Plasma Concentration of Erdafitinib Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks Plasma concentration of Erdafitinib will be reported.
Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate At 3 months CR is defined as the absence of urothelial carcinoma by cystoscopy, confirmed pathologically at first assessment, and negative urine cytology.
Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate Up to 8 weeks pCR rate is defined as percentage of participants with no pathologic evidence of intravesical disease (pT0) and no pathologic evidence of nodal involvement (pN0).
Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0) Up to 8 weeks pT0 rate is defined as percentage of participants with no Pathologic Evidence of Intravesical Disease.
Part 4: Complete Response (CR) in Participants with IR-NMIBC At Month 3 CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy at the first disease evaluation.
Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity Up to 5 years 11 months 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.
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 Up to 5 years 11 months 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.
Part 4: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score Up to 5 years 11 months 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.
Part 4: Percentage of Participants With Significant Change From Baseline in EORTC-QLQ-C30 Scores Up to 5 years 11 months 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.
Trial Locations
- Locations (40)
Urology Associates
🇺🇸Nashville, Tennessee, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Urology Associates of Denver
🇺🇸Lone Tree, Colorado, United States
Urological Research Network
🇺🇸Hialeah, Florida, United States
Advanced Urology Institute
🇺🇸Oxford, Florida, United States
H Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Associated Urological Specialists
🇺🇸Chicago Ridge, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Urology of Indiana
🇺🇸Greenwood, Indiana, United States
Urologic Specialists of Northwest Indiana
🇺🇸Merrillville, Indiana, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Southern Urology LLC
🇺🇸Lafayette, Louisiana, United States
Greater Boston Urology
🇺🇸Plymouth, Massachusetts, United States
Associated Medical Professionals
🇺🇸Syracuse, New York, United States
Levine Cancer Institute, Carolinas HealthCare System
🇺🇸Charlotte, North Carolina, United States
Central Ohio Urology Group
🇺🇸Gahanna, Ohio, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Low Country Urology Clinics
🇺🇸North Charleston, South Carolina, United States
Urology San Antonio Research
🇺🇸San Antonio, Texas, United States
Vancouver Prostate Centre Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
Nova Scotia Health Authority
🇨🇦Halifax, Nova Scotia, Canada
Universitatsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
Marien hospital Herne
🇩🇪Herne, Germany
Universitatsklinikum Munster
🇩🇪Münster, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Rambam Medical Center
🇮🇱Haifa, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv Yafo, Israel
Toyama University Hospital
🇯🇵Toyama-shi, Japan
National Cancer Center
🇰🇷Goyang-Si, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Radboud Umcn
🇳🇱Nijmegen, Netherlands
UMC Utrecht
🇳🇱Utrecht, Netherlands
Fund. Puigvert
🇪🇸Barcelona, Spain
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain