pT3-4 and/or pN1-3 urothelial carcinoma (UC) of the urinary bladder or upper urinary tract after radical cystectomy /radical nephroureterectomy previously treated with at least three cycles of neoadjuvant cisplatin-based chemotherapy or, if neoadjuvant chemotherapy was not administered, ineligible to receive cisplatin-based adjuvant chemotherapy, with evidence of FGFR3 alterations MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Clas
Conditions
Sponsors
EAU Research Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and woman, aged 18 years or older with histological evidence of pT3-4 and/or pN1-3 urothelial cancer (UC) of the urinary bladder or upper urinary tract after radical cystectomy/radical nephroureterectomy. Patients with mixed histologies are required to have a dominant (i.e. at least 50%) urothelial cell carcinoma pattern 2. Previous administration of at least 3 cycles of neoadjuvant cisplatin-based chemotherapy OR, if neoadjuvant chemotherapy was not administered, ineligibility to receive cisplatin-based adjuvant chemotherapy based on Galsky’s criteria, that include at least one of the following: (1) WHO performance status = 2 and/or (2) creatinine-clearance =65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: 1. Any previous receipt of a selective FGFR inhibitor 2. Presence of primary CIS only 3. Presence of another malignancy in the 3 years before enrolment except for basal cell carcinoma or squamous cell carcinoma of the skin, cis of cervix, localised prostate cancer in active surveillance or other non invasive or other indolent malignancy that has undergone potentially curative therapy 4. Presence of pregnancy or lactation or not willing to avoid pregnancy or fathering children 5. Distant metastases (M1 disease) or presence of radiological evidence of disease at baseline 6. Treatment with other investigational drugs, receipt of anticancer medications or radiotherapy of the bladder or upper urinary tract prior to- or after radical surgery 7. Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives (whichever is longer) before the first dose of study Tx 8. Abnormal laboratory parameters: - Total bilirubin = 1.5 × upper limit of normal (ULN; = 2.5 × ULN if Gilbert syndrome); - AST and/or ALT > 2.5 × ULN; - Creatinine clearance = 30 mL/min based on Cockroft-Gault; - Serum phosphate > institutional ULN; - Serum calcium outside of the institutional normal range or serum albumin-corrected calcium outside of the institutional normal range when serum albumin is outside of the institutional normal range 9. History of human immunodeficiency virus infection or active tuberculosis infection 10. Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (exceeding >10 mg daily of prednison equivalent; inhalation steroids are permitted) 11. Evidence of hepatitis B virus or hepatitis C virus active infection or risk of reactivation 12. History of clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from enrollment, NYHA Class III or IV (Appendix 4 of the Protocol) 13. Current evidence of corneal disorder/keratopathy (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc) or retinal disorder (including but not limited to, central serous retinopathy, macular/retinal degeneration, diabetic retino-pathy, retinal detachment, etc) as confirmed by ophthalmologic examination 14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending the required study visits
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate 2-year relapse free survival rate of high-risk patients previously treated with cisplatin-based chemotherapy or ineligibility to receive cisplatin-based adjuvant chemotherapy;Secondary Objective: Secondary objectives are to evaluate safety, tolerability and overall survival. An explorative objective is to evaluate biomarkers of clinical benefit and prognostic biomarkers. These biomarkers will be evaluated at the time of radical surgery, on the tumor tissue, before the administration of the study drug;Primary end point(s): The primary endpoint is the 2-year relapse free survival rate. Relapse free survival is defined as the time from the date of start of study treatment until disease relapse or progression by Investigator determination, or death due to any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated at 2 years from the first dose of study drug | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival. Overall Survival (OS) is defined as the time from the date of start of study treatment to death due to any cause; Safety of study drug assessed as incidence and severity of side effects and changes in laboratory values; An explorative objective is to evaluate biomarkers of clinical benefit and prognostic biomarkers.;Timepoint(s) of evaluation of this end point: Overall survival will be assessed from the date of start of study treatment until death, withdrawal of consent, or the end of the study, whichever occurs first; Adverse event information will be collected from the start of study treatment up to the visit scheduled 30-35 days after the end of study treatment; Biomarkers will be evaluated at the time of radical surgery, on the tumor tissue, before the administration of the study drug | — |
Countries
Austria, Belgium, France, Italy, Spain
Contacts
Public ContactClinical Operations
AMS Advanced Medical Services GmbH
Outcome results
None listed