Phase I 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

Study Identifier:
42756493BLC1003
CT.gov Identifier:
NCT05316155
EudraCT Identifier:
2021-004144-22
EU Trial (CTIS) Number:
2023-506265-65-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

The purpose of the study in Part 1 (dose escalation) is to determine the recommended Phase 2 dose(s) (RP2D[s]) and in Part 2 (dose expansion) is to determine the safety of Erdafitinib Intravesical Delivery System administered at the RP2D(s).

To evaluate the safety, pharmacokinetics (PK), and efficacy of TAR-210 in pts with NMIBC or MIBC with select FGFRalt.

TAR-210 systems with two different erdafitinib release rates were evaluated. Response is assessed every 3 months with continued treatment for up to 1 year if recurrence-free (RF) (C1) or in complete response (CR) (C3).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part 1: Dose Escalation
    • Read More
  • Drug: Experimental: Part 2: Dose Expansion
  • Drug: Experimental: Part 3: RP2D Dose Expansion
  • Drug: Experimental: Part 4: Phase 2 Expansion
  • Drug: Other Names:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • =18 years (or the legal age of consent in the jurisdiction in which the study is taking place)
    • at the time of informed consent.
    • Type of Participant and Disease Characteristics
    • 2. Muscle-invasive or recurrent, non-muscle-invasive urothelial carcinoma of the bladder
    • a) Mixed histology tumors are allowed if urothelial differentiation is predominant (ie, <20% variant histology). However, the presence of micropapillary, signet ring cell, plasmacytoid, neuroendocrine, or sarcomatoid features are exclusionary.
    • b)High-risk papillary disease (Cohorts 1 [Parts 1 and 2] and 2 [Part 2 only]), defined as histologically confirmed high-grade Ta/T1 lesion. Concurrent CIS is not allowed. All visible tumor must be completely resected prior to the start of study treatment and documented on screening cystoscopy
    • c) Intermediate-risk papillary disease (Cohort 3, Parts 1 and 2) defined as all previous tumors being low grade, Ta or T1, and no previous CIS. Cystoscopic documentation of recurrence is sufficient. Negative urine cytology for high grade urothelial carcinoma is required.
    • d) Muscle-invasive disease (Cohort 4, Part 2 only) cT2-T3a, N0. Participants must have a total tumor size =3 cm after TURBT at assessment within 8 weeks prior to the start of study treatment or must have a second debulking TURBT to reduce the tumor(s) to =3 cm in order to be eligible.
    • 3.
    • Activating tumor 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 CLIA-certified or equivalent laboratories, or results from commercially available PCR or NGS tests.
    • 4. Cohorts 1 and 2: 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. unavailable. Participants who received an abbreviated course of BCG due to toxicity are still eligible.
    • BCG experienced is defined as:
    • - Recurrent high-grade Ta/T1 disease within 18 months of completion of prior BCG therapy
    • - Prior BCG (minimumtreatment requirements ):
    • 1)At least 5 of 6 full doses of an initial induction course. Full dose BCG defined as 1 full vial containing a minimum of
    • 1 X 108 colony forming units.
    • OR
    • 2)At least 5 of6 full doses of an initial induction course plus at least 1 maintenance (2 of3 weekly doses) in a 6-month period. One-half dose orone-third dose is allowed during maintenance.
    • Note: Cohort 3 has no predefined prior BCG or intravesical chemotherapy requirement.
    • 5. Cohort 1 only: Refuses or is not eligible for radical cystectomy
    • 6. Cohorts 2 and 4 : willing and eligible for radical cystectomy
    • 7. Cohort 4: Refuses (and understands the risks and benefits of doing so) cisplatin-based combination chemotherapy or is deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
    • - Creatinine clearance (CrCl)<60 mL/min
    • - NCI-CTCAE v.5.0 Grade =2 audiometric hearing loss
    • - NCI-CTCAE v.5.0 Grade =2 peripheral neuropathy
    • 8. Eastern Cooperative Oncology Group (ECOG) performance status score of =2 (Cohorts 1 and 3)or =1 (Cohorts 2 and 4)(see Section 10.9 for ECOG scoring)
    • 9. Adequate bone marrow, liver, and renal function:
    • Bone marrow function (without the support of growth factors or transfusions in preceding 2 weeks):
    • Absolute neutrophil count (ANC) >or=1,000/mm3
    • Platelet count >or=75,000/mm3
    • Hemoglobin >or=8.0 g/dL
    • Liver function:
    • Total bilirubin 1.5 x ULN
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
    • c. Renal function:
    • -Estimated glomerular filtration rate >30 mL/min calculated using the Modified Diet in Renal Disease (MDRD)formula (see Appendix 11)
    • A female participant of childbearing potential must have a negative serum test at screening and a negative urine test (or serum test if required by local regulations) within 72 hours of the first dose (ie, first insertion)of study treatment, and must agree to further serum or urine pregnancy tests during the study.
    • A female participant must be following contraceptive and barrier (see protocol for elaboration)
    • .A male participant must wear a condom(see protocol for elaboration)
    • Must sign an informed consent form (ICF)indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study
    • Willing and able to adhere to the lifestyle restrictions specified in this protocol.
    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 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 primary 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

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Bladder