Studie zum intravesikalen Verabreichungssystem von Erdafitinib bei lokalisiertem Blasenkrebs
Phase-1-Studie zum intravesikalen Abgabesystem Erdafitinib (TAR-210) bei Teilnehmern mit nicht-muskelinvasivem oder muskelinvasivem Blasenkrebs und ausgewählten FGFR-Mutationen oder -Fusionen
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; MoonRISe-2) 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).
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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 approximately up to 7 years 4 months.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienorte
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Dresden, Deutschland, 01307
- Universitatsklinikum Carl Gustav Carus Dresden
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Duisburg, Deutschland, 47169
- Urologicum Duisburg
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Frankfurt am Main, Deutschland, 60590
- Universitatsklinikum Frankfurt
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Herne, Deutschland, 44625
- Marien hospital Herne
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Mettmann, Deutschland, 40822
- Urologie Neandertal Praxis Mettmann
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Münster, Deutschland, 48149
- Universitatsklinikum Munster
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Ulm, Deutschland, 89081
- Universitaetsklinikum Ulm
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Haifa, Israel, 3109601
- Rambam Medical Center
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Haifa, Israel, 3436212
- Carmel Medical Center
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Petah Tikva, Israel, 4941492
- Rabin Medical Center
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Tel Aviv, Israel, 64239
- Tel Aviv Sourasky Medical Center
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Fukuoka, Japan, 810 8563
- National Hospital Organization Kyushu Medical Center
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Kofu, Japan, 400-8506
- Yamanashi Prefectural Central Hospital
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Osaka, Japan, 558-8558
- Osaka General Medical Center
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Toyama, Japan, 930 0194
- Toyama University Hospital
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British Columbia
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Vancouver, British Columbia, Kanada, V5Z 1M9
- Vancouver Prostate Centre Diamond Health Care Centre
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Nova Scotia
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Halifax, Nova Scotia, Kanada, B3H 2Y9
- Nova Scotia Health Authority
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Ontario
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Hamilton, Ontario, Kanada, L8N 4A6
- St Josephs Healthcare Hamilton
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Toronto, Ontario, Kanada, M5G 2M9
- Princess Margaret Cancer Centre
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Nijmegen, Niederlande, 6525 GA
- Radboud Umcn
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Utrecht, Niederlande, 3584 CX
- UMC Utrecht
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Barcelona, Spanien, 08025
- Fund. Puigvert
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Barcelona, Spanien, 08036
- Hosp Clinic de Barcelona
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Barcelona, Spanien, 08035
- Hosp Univ Vall D Hebron
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Córdoba, Spanien, 14004
- Hosp Reina Sofia
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Madrid, Spanien, 28041
- Hosp. Univ. 12 de Octubre
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Madrid, Spanien, 28046
- Hosp. Univ. La Paz
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Madrid, Spanien, 28040
- Hosp Univ Fund Jimenez Diaz
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Valencia, Spanien, 46009
- Instituto Valenciano de Oncologia
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Goyang-si, Südkorea, 10408
- National Cancer Center
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Gwangju, Südkorea, 61469
- Chonnam National University Hospital
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Seoul, Südkorea, 03080
- Seoul National University Hospital
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Seoul, Südkorea, 03722
- Severance Hospital Yonsei University Health System
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Seoul, Südkorea, 06591
- The Catholic University of Korea Seoul St Marys Hospital
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Alabama
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Birmingham, Alabama, Vereinigte Staaten, 35294
- University of Alabama at Birmingham - The Kirklin Clinic
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California
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Los Angeles, California, Vereinigte Staaten, 90033
- University of Southern California
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Colorado
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Lone Tree, Colorado, Vereinigte Staaten, 80124
- Urology Associates of Denver
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Florida
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Hialeah, Florida, Vereinigte Staaten, 33016
- Urological Research Network
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Largo, Florida, Vereinigte Staaten, 33771
- Advanced Urology Institute
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Orlando, Florida, Vereinigte Staaten, 32804
- Advent Health Orlando
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Oxford, Florida, Vereinigte Staaten, 34484
- Advanced Urology Institute 1
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Tampa, Florida, Vereinigte Staaten, 33612
- H Lee Moffitt Cancer Center
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Illinois
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Chicago, Illinois, Vereinigte Staaten, 60611
- Northwestern University
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Chicago Ridge, Illinois, Vereinigte Staaten, 60415
- Associated Urological Specialists
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Indiana
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Greenwood, Indiana, Vereinigte Staaten, 46143
- Urology of Indiana
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Merrillville, Indiana, Vereinigte Staaten, 46410
- Urologic Specialists of Northwest Indiana
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Kentucky
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Lexington, Kentucky, Vereinigte Staaten, 40506
- University of Kentucky
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Louisiana
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Lafayette, Louisiana, Vereinigte Staaten, 70508
- Southern Urology LLC
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Massachusetts
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Plymouth, Massachusetts, Vereinigte Staaten, 02360
- Greater Boston Urology
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Missouri
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St Louis, Missouri, Vereinigte Staaten, 63141
- Specialty Clinical Research of St Louis
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New Jersey
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Hackensack, New Jersey, Vereinigte Staaten, 07601
- Hackensack University Medical Center Urology
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New York
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Syracuse, New York, Vereinigte Staaten, 13210
- Associated Medical Professionals
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North Carolina
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Charlotte, North Carolina, Vereinigte Staaten, 28204
- Levine Cancer Institute, Carolinas HealthCare System
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Ohio
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Gahanna, Ohio, Vereinigte Staaten, 43230
- Central Ohio Urology Group
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South Carolina
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Myrtle Beach, South Carolina, Vereinigte Staaten, 29572
- Carolina Urologic Research Center
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North Charleston, South Carolina, Vereinigte Staaten, 29406
- Low Country Urology Clinics
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Tennessee
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Nashville, Tennessee, Vereinigte Staaten, 37209
- Urology Associates
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Texas
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Austin, Texas, Vereinigte Staaten, 78745
- Urology Austin
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San Antonio, Texas, Vereinigte Staaten, 78229
- Urology San Antonio Research
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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-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
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 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. 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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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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. |
Erdafitinib intravesical delivery system will be administered.
Andere Namen:
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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. |
Erdafitinib intravesical delivery system will be administered.
Andere Namen:
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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. |
Erdafitinib intravesical delivery system will be administered.
Andere Namen:
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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. |
Erdafitinib intravesical delivery system will be administered.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Parts 1 to 3: Number of Participants with Adverse Events (AEs)
Zeitfenster: Up to approximately 7 years 4 months
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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. |
Up to approximately 7 years 4 months
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Parts 1 to 3: Number of Participants with AEs by Severity
Zeitfenster: Up to approximately 7 years 4 months
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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. |
Up to approximately 7 years 4 months
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Part 1: Number of Participants with Dose-limiting Toxicity (DLT)
Zeitfenster: Up to 28 days
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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. |
Up to 28 days
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Part 4: Overall Complete Response (CR) in Participants with Intermediate Risk-Non-Muscle Invasive Bladder Cancer (IR-NMIBC)
Zeitfenster: Up to approximately 7 years 4 months
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Overall CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy. |
Up to approximately 7 years 4 months
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Parts 1 to 3: Plasma Concentration of Erdafitinib
Zeitfenster: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
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Plasma concentration of Erdafitinib will be reported. |
Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
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Parts 1 to 3: Urine Concentration of Erdafitinib
Zeitfenster: Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
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Urine concentration of Erdafitinib will be reported. |
Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
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Parts 1 to 3: Cohorts 1 and 2: Recurrence-Free Survival (RFS)
Zeitfenster: Up to approximately 7 years 4 months
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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. |
Up to approximately 7 years 4 months
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Parts 1 to 3: Cohort 3 and 5: Complete Response (CR) Rate
Zeitfenster: At 3 months
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CR is defined as the absence of urothelial carcinoma by cystoscopy, confirmed pathologically at first assessment, and negative urine cytology. |
At 3 months
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Parts 1 to 3: Cohort 3 and 5: Duration of CR
Zeitfenster: Up to approximately 7 years 4 months
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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. |
Up to approximately 7 years 4 months
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Parts 1 to 3: Cohort 4: Pathological Complete Response (pCR) Rate
Zeitfenster: Up to 8 weeks
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pCR rate is defined as percentage of participants with no pathologic evidence of intravesical disease (pT0) and no pathologic evidence of nodal involvement (pN0). |
Up to 8 weeks
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Parts 1 to 3: Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0)
Zeitfenster: Up to 8 weeks
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pT0 rate is defined as percentage of participants with no Pathologic Evidence of Intravesical Disease. |
Up to 8 weeks
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Parts 1 to 3: Cohort 4: Rate of downstaging to Less than (<) pT2
Zeitfenster: Up to 8 weeks
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Rate of downstaging to <pT2 is defined as percentage of participants with pT stage <2. |
Up to 8 weeks
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Part 4: Duration of CR (DoCR) in Participants with IR-NMIBC
Zeitfenster: Up to approximately 7 years 4 months
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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. |
Up to approximately 7 years 4 months
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Part 4: Complete Response (CR) at 3 Months in Participants with IR-NMIBC
Zeitfenster: At Month 3
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CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy at the first disease evaluation. |
At Month 3
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Part 4: Transurethral Resection of the Bladder Tumor (TURBT)-Free Survival in Participants With IR-NMIBC
Zeitfenster: Up to approximately 7 years 4 months
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Participants with TURBT-free survival will be reported. |
Up to approximately 7 years 4 months
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Part 4: Number of Participants with Treatment-Emergent Adverse Event (TEAEs) by Severity
Zeitfenster: Up to approximately 7 years 4 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. |
Up to approximately 7 years 4 months
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Part 4: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score
Zeitfenster: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 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. |
At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)
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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
Zeitfenster: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 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. |
At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)
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Part 4: Percentage of Participants With Clinically Meaningful Change From Baseline in EORTC-QLQ-C30 Scores
Zeitfenster: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 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. |
At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)
|
|
Part 4: Percentage of Participants With Clinically Meaningful Change From Baseline in EORTC-QLQ-NMIBC24 Scores
Zeitfenster: At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 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. |
At baseline (Week 0), Weeks 12, 24, 36, 48, and at completion or discontinuation of study treatment (up to approximately 7 years 4 months)
|
Mitarbeiter und Ermittler
Ermittler
- Studienleiter: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Urogenitale Erkrankungen
- Urogenitale Neoplasmen
- Neubildungen nach Standort
- Neubildungen
- Männliche Urogenitalerkrankungen
- Urologische Erkrankungen
- Weibliche Urogenitalerkrankungen
- Weibliche Urogenitalerkrankungen und Schwangerschaftskomplikationen
- Neubildungen nach histologischem Typ
- Neubildungen, Drüsen und Epithelien
- Urologische Neubildungen
- Karzinom
- Erkrankungen der Harnblase
- Neoplasien der Harnblase
- Nicht-muskelinvasive Blasenneoplasien
- Erdafitinib
Andere Studien-ID-Nummern
- CR109115
- 42756493BLC1003 (Andere Kennung: Janssen Research & Development, LLC)
- 2021-004144-22 (EudraCT-Nummer)
- 2023-506265-65-00 (Registrierungskennung: EUCT number)
- 2023 (US NIH Stipendium/Vertrag)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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