Advanced Urothelial Cancer bladder cancer
Conditions
Interventions
Study drug: 
The study drug will be provided in either a tablet form or be given to the 
subject through an intravenous (IV) infusion like normal chemotherapy.
Erdafitinib: 
Subject will take Erdafitinib tablets once per day with a glass of water (about 
240mL). Study doctor may increase or decrease the dose depending on how the 
body reacts to the drug. The dose of study drug may be changed or stopped if 
subject has a side effect. 
The tablets can be taken with or without food but they should be swallowed 
whole and must not be dissolved in water. Each dose should be taken at about 
the same time each day. If a dose is missed it can be taken up to 6 hours after 
the time it is usually taken and the normal dosing time resumed the following 
day. If it has been more than 6 hours since the dose was missed, that dose 
should be skipped and treatment continued as normal the next day. If vomiting 
occurs when the dose is taken, no replacement dose should be taken. Subject 
should not eat grapefruit or Seville oranges during the study treatment period 
as it could interfere with the study drug in the body.
On Day 14 of Cycle 1 and Day 1 of Cycle 2 the subject will need to come into 
clinic to have blood samples taken to find out the level of erdafitinib in 
their blood. On these days, subject may need to take their usual dose of 
erdafitinib at the clinic
the study staff will let subject know if this is the 
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. >=18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) 2. Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components (<50% overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable 3. Criterion amended per Amendment 2: 3.1 Metastatic or surgically unresectable urothelial cancer 4. Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization 5. Criterion modified per Amendment 5: 5.3 Cohort 1: Prior treatment with an anti-PD-(L)1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Prior treatment with an anti-PD-(L)1 agent could have been given as neo-adjuvant, adjuvant, or in metastatic line of treatment as frontline or maintenance therapy, as follows: * together with chemotherapy or as maintenance therapy * together with chemotherapy in metastatic setting * for superficial cancer (early disease/non-muscle invasive bladder cancer), OR in neo-adjuvant OR adjuvant setting. If these subjects did not relapse within a year of their last dose of anti-PD-(L)1, this will not be counted as a prior line of systemic treatment. These subjects will however still be eligible only for Cohort 1. Cohort 2: No prior treatment with an anti-PD-(L)1 agent; only 1 line of prior systemic treatment. Note: Subjects who received neoadjuvant or adjuvant chemotherapy or immunotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting. 6. Subjects must meet appropriate molecular eligibility criteria (as determined by central laboratory screening or local or by local historical test results (from tissue or blood) performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified or regional equivalent laboratory using the following methods: local next-generation sequencing (NGS), direct digital counting methods, or the Qiagen Therascreen FGFR Rotor-Gene Q (RGQ) reverse transcription polymerase chain reaction (RT-PCR) test. Tumors must have at least 1 of the following translocations: FGFR2-BICC1, FGFR2-CASP7, FGFR3-TACC3, FGFR3-BAIAP2L1; or 1 of the following FGFR3 gene mutations: R248C, S249C, G370C, Y373C. 7. ECOG performance status Grade 0, 1, or 2 (Attachment 1) 8. Criterion amended per Amendment 2: 8.1 Criterion modified per Amendment 3: 8.2.Criterion modified per Amendment 4: 8.3 Criterion modified per Amendment 5: 8.4 Adequate bone marrow, liver, and renal function: a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding 2 weeks): * Absolute neutrophil count (ANC) >1,500/mm3 * Platelet count >75,000/mm3 (>=100,000/mm3 for Cohort 1 subjects at sites choosing vinflunine chemotherapy) * Hemoglobin >8.0 g/dL (without transfusion or demonstrate stability, ie; no significant decline in hemoglobin, for 2 weeks after transfusion) b. Liver function: * Total bilirubin <=1.5 x instit
Exclusion criteria
Exclusion criteria: 1. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization. 2. Criterion amended per Amendment 2: 2.1 Criterion modified per Amendment 3: 2.2 Active malignancies (ie, requiring treatment change in the last 24 months). The only allowed exceptions are: * urothelial cancer. * skin cancer treated within the last 24 months that is considered completely cured. * localized prostate cancer with a Gleason score of 6 (treated within the last 24 months or untreated and under surveillance). * localized prostate cancer with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence. 3. Symptomatic central nervous system metastases. 4. Received prior FGFR inhibitor treatment. 5. Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients 6. Criterion amended per Amendment 2: 6.1 Criterion modified per Amendment 3. 6.2 Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade. 7. History of uncontrolled cardiovascular disease including: a. unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac arrest, or known congestive heart failure Class III-V (Attachment 3) within the preceding 3 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months. b. QTc prolongation as confirmed by triplicate assessment at screening (Fridericia; QTc >480 milliseconds). c. Pulmonary embolism or other venous thromboembolism (VTE) within the preceding 2 months. 8. Known active AIDS (human immunodeficiency virus (HIV) infection), unless the subject has been on a stable anti-retroviral therapy regimen for the last 6 months or more, has had no opportunistic infections in the last 6 months, and has CD4 count >350. 9. Criterion amended per Amendment 3: 9.1 Known active hepatitis B or C infection (unless polymerase chain reaction [(PCR]-negative [according to local laboratory range] on all available tests for the past 6 months). 10. Criterion amended per Amendment 3: 10.1 Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, neuropathy, hearing loss). 11. Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions. 12. Major surgery within 4 weeks before randomization. 13. Criterion amended per Amendment 2: 13.1 Criterion modified per Amendment 3: 13.2 Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Examples include ongoing active infection requiring systemic therapy and uncontrolled ongoing medical conditions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: The primary endpoint is overall survival (OS). Overall survival is measured from the date of randomization to the date of the subject*s death. If the subject is alive or the vital status is unknown, the subject will be censored at the date the subject was last known to be alive. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: • PFS: duration in days from the date of randomization to the date of disease progression (assessed per RECIST v1.1 by the investigator) or relapse from CR or death, whichever is reported first. For subjects who do not have disease progression and are alive, as well as for subjects with unknown disease progression or unknown survival status as of the clinical cutoff date, PFS will be censored at the date of the last adequate disease assessment. If there is no postbaseline tumor assessment for a subject, PFS will be censored on the date of randomization. Refer to the Statistical Analysis Plan (SAP) for further details regarding censoring rules. Adequate disease assessment is defined as having sufficient evidence to indicate correctly that progression has or has not occurred. • ORR: the proportion of subjects who achieve complete response or partial response, as assessed per RECIST v1.1 by the investigator. • Change from baseline in patient-reported health status and physical functioning scales of the Functional Assessment of Cancer Therapy - Bladder Cancer (FACT-Bl), Patient-Global Impression of Severity (PGIS), and utility and visual analog scale of the European Quality of Life-5 Dimensions-5 Levels Questionnaire (EQ-5D-5L). • DOR: for responders, duration in days from the date of initial documentation of a response to the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death. The censoring is similar to PFS. • Safety: collection of adverse event, clinical laboratory values, electrocardiograms, vital signs, ophthalmologic evaluations, physical examinations • Oral clearance, area under the plasma concentration-time curve (and other parameters, as needed and as data permits) will be estimated using a population approach. | — |
Countries
Netherlands
Outcome results
None listed