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
- Conditions
- Localized Bladder CancerNon-Muscle-Invasive or Muscle-Invasive Bladder Cancer10038363
- Registration Number
- NL-OMON53522
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 20
Age 1. >=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. Recurrent, non-muscle-invasive or 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. Visible disease must be present at the time of first
TAR-210 insertion. d) Muscle-invasive disease (Cohort 4, Part 2 only) cT2-T3a,
N0. Participants must have a total tumor size <=3 cm after TURBT at cystoscopic
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. 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 ): 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. 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: a. Bone marrow
function (without the support of growth factor
Medical Conditions 1. Concurrent extra-vesical (ie, urethra, ureter, renal
pelvis) transitional cell carcinoma of the urothelium. 2. Prior treatment with
an FGFR inhibitor. 3. Known hypersensitivity to any study component including:
- Erdafitinib (or other drug excipients) or chemically related drugs, - TAR-210
device constituent materials, - UPC materials. Refer to the TAR-210 IB for
complete information on excipients, device constituent materials, and UPC
materials 4. Received pelvic radiotherapy <=6 months prior to the planned start
of study treatment. If received pelvic radiotherapy >6 months prior to the
start of study treatment, there must be no cystoscopic evidence of radiation
cystitis. 5. Presence of any bladder or urethral anatomic feature that in the
opinion of the investigator may prevent the safe placement, indwelling use, or
removal of TAR-210. 6. Indwelling urinary catheter. Intermittent
catheterization is acceptable. 7. Cystoscopic evidence of bladder perforation
unless such perforation has resolved prior to dosing. 8. Bladder post-void
residual volume (PVR) >350 mL after second voided urine. 9. History of
clinically significant polyuria with recorded 24-hour urine volumes >4,000 mL.
10 Subjects with active bladder stones or history of bladder stones <6 months
prior to the start of study treatment. 11. Active malignancies (ie, progressing
or requiring treatment change in the last 24 months) other than the disease
being treated under study. Potential allowed exceptions include the following
(others maybe allowed with sponsor approval) a. skin cancer (non-melanoma or
melanoma)that is considered completely cured. b. non-invasive cervical cancer
that is considered completely cured. c. adequately treated lobular carcino main
situ(LCIS)and ductal CIS d. history of localized breastcancer and receiving
antihormonal agents e. history of localized prostate cancer (N0M0) and
receiving androgen deprivation therapy f. Localized prostate cancer (N0M0) -
with a Gleason score of 6, treated within the last 24 months or untreated and
under surveillance, - with a Gleason score of3+4 that has been treated more
than 6 months prior to full study Screening and considered to have a very low
risk of recurrence, - or history of localized prostate cancer and receiving
androgen deprivation therapy and considered to have a very low risk of
recurrence. 12. Current central serous retinopathy or retinal pigment
epithelial detachment of any grade. 13. History of uncontrolled cardiovascular
disease including: - Any of the following within 3 months prior to the start of
study treatment: unstable angina, myocardial infarction, ventricular
arrhythmias or clinically significant atrial arrythmias (eg, atrial
fibrillation with uncontrolled rate), cardiac arrest, or known congestive New
York Heart Association Class III-IV heart failure (Appendix 10),
cerebrovascular accident, or transient ischemic attack. - Pulmonary embolism or
other venous thromboembolism within 1 month prior to the planned start of study
treatment. 14. Active or chronic hepatitis B or C infection according to the
following criteria: - Seropositive for hepatitis B: defined by a positive test
for hepatitis B surface antigen [HBsAg]. Participants with resolved infection
(ie, participants who are HbsAg negative with antibod
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Endpoints:<br /><br>*Incidence and severity of AEs, including dose-limiting toxicity (DLT)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Endpoints: *Plasma and urine concentration-time profiles and PK parameters for<br /><br>erdafitinib Cohorts 1 and 2: * Recurrence-free survival (RFS) Cohort 3: *<br /><br>Complete response (CR) rate * Duration of CR Cohort 4: * Pathological complete<br /><br>response (pCR) rate * pT0 rate * Rate of downstaging to</p><br>