This trial will assess the 6-month complete response rate and toxicity profile of oral dovitinib therapy in BCG-refractory urothelial carcinoma patients with tumors with FGFR3 mutations or over-expression who are ineligible for or refusing cystectomy.
OUTLINE: This is a multi-center study. * Dovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. Day 12 assessments are intended to be performed on the last dosing day of the 2nd week in cycle 1 and cycle 2 and day 26 assessments are intended to be performed on the last dosing day of the 4th week in cycle 1 and cycle 2. * Standard of Care: Cystoscopy with tumor biopsy, bladder biopsy, urine cytology * Physician discretion: Anti-emetic medications and/or colony stimulating growth factors ECOG performance status 0 - 2 Hematopoietic: * White blood cell count (WBC) \> 3.0 K/mm3 * Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 * Platelets ≥ 100 K/mm3 * Hemoglobin (Hgb) ≥ 9 g/dL Hepatic: * Serum total bilirubin: ≤ 1.5 x Upper limit of normal (ULN) * Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3.0 x ULN Renal: * Serum creatinine ≤ 1.5 x ULN or serum creatinine \> 1.5 - 3 x ULN if calculated creatinine clearance (CrCl) is ≥ 30 mL/min using the Cockcroft-Gault equation Cardiovascular: No impaired cardiac function or clinically significant cardiac diseases, including any of the following: * History or presence of serious uncontrolled ventricular arrhythmias * Clinically significant resting bradycardia * LVEF assessed by 2-D echocardiogram (ECHO) \< 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA), \< 45% or lower limit of normal (whichever is higher) * Myocardial Infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)within 6 months prior to starting study drug
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Dovitinib will be administered 500mg orally in a 5 days on, 2 days off dosing schedule. Day 12 assessments are intended to be performed on the last dosing day of the 2nd week in cycle 1 and cycle 2 and day 26 assessments are intended to be performed on the last dosing day of the 4th week in cycle 1 and cycle 2.
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Fox Chase Cancer Center Extramural Research Program
Rockledge, Pennsylvania, United States
Determine 6-Month Complete Response Rate
The 6-month complete response rate is defined as the proportion of patients treated with dovitinib with no evidence of any remaining urothelial carcinoma tumors of any T-stage (including Tis) present within the bladder as assessed by standard of care cystoscopic examination with transurethral resection of bladder tumor (TURBT) and urine cytology performed at 6 months after initiation of study therapy.
Time frame: 6 months
Determine 1-Year Relapse-Free Survival Rate
The 1-year relapse free survival rate is defined as the proportion of patients treated with dovitinib with no evidence of any remaining urothelial carcinoma tumors at 12 months of follow-up.
Time frame: 12 months
Determine Rate of Progression to Muscle-Invasive Stage
The rate of progression to muscle-invasive stage for dovitinib is defined as the proportion of patients with clinical or pathologic progression to muscle-invasive stages (i.e., T2-T4) at any time point on study.
Time frame: 12 months
Determine 3-Month and 6-Month Partial Response Rates
The 3- and 6-month partial response rates are defined as the proportion of patients treated with persistent but reduced T-stage tumors on post-therapy TURBT (i.e., T1 ≥ Ta; T1+Tis ≥ T1).
Time frame: 6 months
Characterize Treatment-related Toxicity Rates
Treatment-related toxicity rates will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All grade 3-4 adverse events and other adverse events occurring in more than 20% of patients are reported.
Time frame: 12 months
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