Advanced Urothelial Cancer MedDRA version: 21.1 Level: LLT Classification code 10077840 Term: Urothelial cancer of renal pelvis System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
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 (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, i.e., no significant decline in hemoglobin, for 2 wks after transfusion) b. Liver function: -Total bilirubin 1.5xULN [=1xULN for Cohort 1 subjects at sites choosing docetaxel chemotherapy] -Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5x institutional ULN or =5x institutional ULN for subjects with liver metastases (For subjects in Cohort 1 at sites choosing docetaxel chemotherapy, both the ALT and AST values must be =1.5×ULN concomitant with alkaline phosphatase of =2.5×ULN) c. Renal function: Creatinine clearance >30 L/min either directly measured via 24-hour urine collection or calculated using Cockcro
Exclusion criteria
Exclusion criteria: For All Subjects 1. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 d prior to randomization 2. Active malignancies (ie, requiring treatment change in the last 24 m). The only allowed exceptions are: •urothelial cancer •skin cancer treated within the last 24 m that is considered completely cured •localized prostate cancer with a Gleason score of 6 (treated within the last 24 m or untreated and under surveillance) •localized prostate cancer with a Gleason score of 3+4 that has been treated more than 6 m 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. 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 m; cerebrovascular accident or transient ischemic attack within the preceding 3 m 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 m 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 m or more, has had no opportunistic infections in the last 6 m, and has CD4 count >350 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 6m). 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 wks before randomization 13. 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. For Cohort 1 Subjects 14.2 Criterion modified per Amendment 4. 14.3 For those participating , at sites using docetaxel: has a history of severe hypersensitivity reaction (eg, generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to either docetaxel or to other drugs formulated with polysorbate and paclitaxel. At sites using docetaxel, subjects with evidence of interstitial lung disease or active non-infectious pneumonitis are excluded. For Cohort 2 Subjects 15. Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic or immunosuppressive agents. Subjects with vitiligo, diabetes Type I, or resolved childhood asthma/atopy would be an exception to this rule. Subjects who require intermittent use of bronchodilators, inhaled st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in subjects with advanced urothelial cancer harboring selected FGFR aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death-ligand 1 (PD-[L]1) agent (cohort 1), or 1 prior treatment not containing an anti-PD-(L)1 agent (cohort 2). The primary endpoint of overall survival will be evaluated in 2 cohorts: - Cohort 1: erdafitinib versus chemotherapy (docetaxel or vinflunine) [subjects who have received prior anti-PD(L)1 agent] - Cohort 2: erdafitinib versus pembrolizumab [subjects who have not received prior anti-PD(L)1 agent] ;Secondary Objective: - To evaluate progression-free survival (PFS) of subjects treated with erdafitinib versus chemotherapy or pembrolizumab - To evaluate the objective response rate (ORR) of subjects treated with erdafitinib versus chemotherapy or pembrolizumab - To evaluate the health-related quality of life (HRQOL) of subjects treated with erdafitinib versus chemotherapy or pembrolizumab - To evaluate the duration of response (DOR) for subjects treated with erdafitinib versus chemotherapy or pembrolizumab - To characterize the safety profile of subjects treated with erdafitinib versus chemotherapy or pembrolizumab - To evaluate the population PK of erdafitinib;Primary end point(s): 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 ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 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),Time Until Symptom Deterioration (subset of FACT-Bl items), 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 ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed