Study of Erdafitinib Intravesical Delivery System for Localized Bladder Cancer

Urinary Bladder Neoplasms Clinical Trial

Official title:

Phase 1 Study of Erdafitinib Intravesical Delivery System (TAR-210) in Participants With Non- Muscle-Invasive or Muscle-Invasive Bladder Cancer and Selected FGFR Mutations or Fusions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05316155
• Other study ID #: CR109115
• Secondary ID: 42756493BLC10032
• Status: Recruiting
• Phase: Phase 1
• Start date: April 11, 2022
• Est. completion date: March 31, 2028

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 3 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: March 31, 2028
• Est. primary completion date: March 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Receptors, Fibroblast Growth Factor
• Urinary Bladder Neoplasms

Intervention

Drug:
• Erdafitinib Intravesical Delivery System
Erdafitinib intravesical delivery system will be administered.

Locations

Country	Name	City	State
Germany	Universitatsklinikum Frankfurt	Frankfurt am Main
Germany	Marien hospital Herne	Herne
Germany	Universitatsklinikum Munster	Münster
Germany	Universitaetsklinikum Ulm	Ulm
Korea, Republic of	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. Mary's Hospital	Seoul
Netherlands	Radboud Umcn	Nijmegen
Netherlands	UMC Utrecht	Utrecht
Spain	Fund. Puigvert	Barcelona
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. 12 de Octubre	Madrid
United States	Levine Cancer Institute, Carolinas HealthCare System	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Southern California	Los Angeles	California
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Urology Associates	Nashville	Tennessee
United States	Urology San Antonio Research	San Antonio	Texas
United States	H Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Germany,  Korea, Republic of,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 5 years 3 months
Primary	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.	Up to 5 years 3 months
Primary	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.	Up to 28 days
Secondary	Plasma Concentration of Erdafitinib	Plasma concentration of Erdafitinib will be reported.	Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
Secondary	Urine Concentration of Erdafitinib	Urine concentration of Erdafitinib will be reported.	Cohorts 1, 3 and 5: up to 6 months; Cohort 2 and 4: up to 8 weeks
Secondary	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.	Up to 5 years 3 months
Secondary	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.	At 3 months
Secondary	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.	Up to 5 years 3 months
Secondary	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).	Up to 8 weeks
Secondary	Cohort 4: No Pathologic Evidence of Intravesical Disease (pT0)	pT0 rate is defined as percentage of participants with no Pathologic Evidence of Intravesical Disease.	Up to 8 weeks
Secondary	Cohort 4: Rate of downstaging to Less than (<) pT2	Rate of downstaging to	Up to 8 weeks