Dovitinib Lactate in Treating Patients With Refractory or Stage 0-I Bladder Cancer With FGFR3 Mutations or Overexpression

Inclusion Criteria

• Histologically confirmed early stage urothelial carcinoma of the bladder defined as Ta, T1, or Tis stage; tumor staging must be confirmed by TURBT performed within 42 days prior to registration
• Presence of either an FGFR3 mutation or FGFR3 over-expression within bladder tumor tissue. FGFR3 mutations in exons 7, 10, and 15 will be assessed by polymerase chain reaction (PCR)-single strand conformation polymorphism (PCR-SSCP) sequencing analysis utilizing the CertNDx® molecular grading assay performed in the Clinical Laboratory Improvement Amendments (CLIA)-certified Predictive Biosciences™ laboratories; FGFR3 over-expression will be assessed by standard immunohistochemistry (IHC) analysis performed within the Indiana University Simon Cancer Center Immunohistochemistry (IHC) Core Lab
• Documented BCG-refractory disease defined as failure to achieve a tumor free state after at least 2 prior induction courses of intravesical BCG therapy; NOTE: For patients with residual non-invasive tumors (i.e. Ta, T1, Tis) after an initial 6-week induction course of intravesical BCG therapy, a second induction course of intravesical BCG therapy is required; patients with persistent non-invasive tumors (i.e. Ta, T1, Tis) despite an initial 6-week and second induction intravesical BCG therapy course are considered BCG-refractory and, therefore, eligible for study; patients with non-invasive tumor recurrences (i.e. Ta, T1, Tis) after only an initial 6-week induction course of intravesical BCG therapy are considered BCG-resistant and not eligible for study until persistent non-invasive tumor (i.e. Ta, T1, Tis) is demonstrated after a second induction course of intravesical BCG therapy has been administered; there is no maximum limit on the number of prior BCG therapy courses; in addition, there is no maximum limit on the number of prior non-BCG intravesical therapy courses (i.e. gemcitabine, valrubicin, interferon, mitomycin C, etc.)
• Medically unfit to undergo cystectomy or electively choosing to forego cystectomy
• Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO]) performance status 0 or 1 or 2
• White blood cell count (WBC) >= 3.0 K/mm^3
• Absolute neutrophil count (ANC) >= 1.5 K/mm^3
• Platelets >= 100 K/mm^3
• Hemoglobin (Hgb) >= 9 g/dL
• Serum total bilirubin: =< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN
• 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 Cockroft-Gault equation
• Patients who give a written informed consent obtained according to local guidelines

Exclusion Criteria

• Patients with muscle-invasive (i.e. T2, T3, T4), locally advanced non-resectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration; the required radiographic imaging includes: * Abdomen/Pelvis – computed tomography (CT) scan * Chest – chest x-ray or CT scan
• Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma
• Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, clinically localized prostate cancer, biochemically relapsed non-metastatic prostate cancer (i.e. prostate specific antigen [PSA] only disease), or skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer)
• Patients who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies =< 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
• Patients who have received targeted prior VEGFR or FGFR-targeted agents (i.e. sunitinib, pazopanib, sorafenib, bevacizumab, axitinib, etc.)
• Patients who have had radiotherapy =< 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
• Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =< 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device =< 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
• Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: * 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 ** Left ventricular ejection fraction (LVEF) assessed by 2-dimensional (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) ** Any of the following within 6 months prior to starting study drug: 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) ** Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication(s) * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) * Cirrhosis, chronic active hepatitis or chronic persistent hepatitis * Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) * Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin; full-dose anti-coagulation with low molecular weight heparin is permitted * Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
• Pregnant or breast-feeding women
• Women of child-bearing potential, who are biologically able to conceive and not employing two forms of highly effective contraception; two forms of highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicide; diaphragm with spermicide; intra-uterine device); oral, implantable, or injectable contraceptives that may be affected by cytochrome P450 interactions are not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test =< 14 days prior to starting study drug
• Fertile males not willing to use contraception
• Patients unwilling or unable to comply with the protocol