A Study of Erdafitinib Compared with Vinflunine or Docetaxel or Pembrolizumab in Subjects with Advanced Urothelial Cancer
- Conditions
- Advanced Urothelial CancerMedDRA version: 21.1Level: LLTClassification code 10077840Term: Urothelial cancer of renal pelvisSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002932-18-AT
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 630
1. =18yrs 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. Metastatic or surgically unresectable urothelial cancer
4. Documented PD, defined as any progression that requires a change in treatment, prior to randomization.
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 PD within 12m of the last dose are considered to have received systemic therapy in the metastatic setting.
6.1 Subjects must meet appropriate molecular eligibility criteria (as determined by central laboratory screening 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
8.4. Adequate bone marrow, liver, and renal function:
a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding 2wks):
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, i.e., no significant decline in hemoglobin, for 2wks after transfusion)
b. Liver function:
-Total bilirubin <1.5 x ULN OR direct bilirubin =ULN for subjects with total bilirubin levels >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 mL/min either directly measured via 24hr urine collection or calculated using Cockcroft-Gaultd
d.Criterion deleted per amdt 3.
e. Phosphate: <ULN
For All Subjects
1. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30d prior to randomization
2.1 Active malignancies (ie, requiring treatment change in the last 24m). The only allowed exceptions are:
•urothelial cancer
•skin cancer treated within the last 24m that is considered completely cured
•localized prostate cancer with a Gleason score of 6 (treated within the last 24m or untreated and under surveillance)
•localized prostate cancer with a Gleason score of 3+4 that has been treated more than 6m 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
6.2 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 3m; cerebrovascular accident or transient ischemic attack within the preceding 3m
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 2m
8. Known active AIDS (human immunodeficiency virus (HIV) infection), unless the subject has been on a stable anti retroviral therapy regimen for the last 6m or more, has had no opportunistic infections in the last 6m, 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 4wks before randomization
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.
For Cohort 1 Subjects
14.2Criterion 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 steroids, or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method