Clofarabine Therapy in Locally Advanced or Metastatic Urothelial Carcinoma

Inclusion Criteria: * Patients with histologically or cytologically confirmed urothelial carcinoma, radiologically documented metastatic or unresectable locally advanced disease * Patients who have already received standard treatment and did not benefit from it, or patients who have refused standard therapy * Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count (ANC) greater than or equal to 1500. * White blood cell (WBC) count greater than 3.0. * Platelets greater than or equal to 100. * Hemoglobin greater than 9.0 g/dL. * Adequate hepatobiliary function as indicated by the following laboratory values: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * Adequate renal function as indicated by the following laboratory values: Serum creatinine ≤ 1.0 mg/dL; if serum creatinine \> 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \> 60 mL/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation * Adequate cardiac function (NYHA cardiac III-IV excluded) * Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment * Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment * Willing and able to provide informed consent Exclusion Criteria: * Received previous treatment with clofarabine * Current concomitant chemotherapy, radiation therapy, or immunotherapy * Prior radiation therapy to the pelvis * Currently participation in other investigational drug studies or having received other investigational drugs within the previous 30 days * Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment. In particular: a) New York Heart Association classification stage II, III, or IV congestive heart failure; b) Coronary artery disease or arteriosclerotic cardiovascular disease (angina, myocardial infraction) within 3 months of first dose of study drug; c) Any other primary cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia. * Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). * Any medical condition that requires chronic use of oral high-dose corticosteroids (in excess of 1 mg/kg/day) (low-dose corticosteroid for pre-medication purposes are allowed). * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results * Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: Patients with treated non-melanoma skin cancer, in-situ carcinoma or cervical intraepithelial neoplasia regardless of disease-free duration are eligible for this study if definitive treatment for the condition has been completed; Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on PSA value are eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed * Had currently active gastrointestinal disease, or prior surgery that might affect the ability of the participants to absorb oral Clofarabine. * Had prior treatment with a known nephrotoxic drug within 2 weeks of the first dose of study drug, unless the participants had a calculated GFR \>30 at 2 time points no \<7 days apart during the 2- week period prior to the first dose of study drug. * Positive human immunodeficiency virus (HIV) test. * Female patients who are pregnant/breastfeeding.