Cabozantinib for Advanced Urothelial Cancer

* INCLUSION CRITERIA: Cohort 1 only (urothelial progressive disease) * Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Confirmation may be obtained from any Clinical Laboratory Improvement Amendments (CLIA) certified lab. * Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging. * Patients must have at least one measurable site of disease Cohort 2 only (Bone-only) * Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Confirmation may be obtained from any CLIA certified lab. * Patients must not have measurable progressive disease * Patient must have appearance of at least one new bone lesion. Cohort 3 (Rare histologies) * Patient must have a histologically confirmed diagnosis of non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis including but not limited to squamous cell, neuroendocrine, adenocarcinoma including urachal and sarcomatoid. Confirmation may be obtained from any CLIA certified lab. * Patients must have progressive metastatic disease. Progressive disease will be defined as new or progressive lesions on cross-sectional imaging. * Patients must have at least one measurable site of disease All cohorts * Patients must have been previously treated, as defined by treatment with at least one prior cytotoxic regimen or agent. * Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of cabozantinib in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60% * Adequate organ function as defined by the following criteria: * Hemoglobin greater than or equal to 9 g/dL * Absolute neutrophil count (ANC) greater than or equal to 1500/microL * Platelets greater than or equal to 75,000/L * Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) less than or equal to 3.0 times upper limit of normal (ULN); less than or equal to 5.0 times ULN in cases of liver metastases * Total serum bilirubin less than or equal to 1.5 times the upper limit of normal (ULN). For subjects with known Gilberts disease or similar syndrome with slow conjugation of bilirubin, total bilirubin less than or equal to 3.0 mg/dL * Serum creatinine less than or equal to 1.5 X institutional upper limits of normal or for patients with creatinine levels above 1.5 x institutional normal: creatinine clearance greater than or equal to 50 mL/min/1.73 m\^2 by 24 hour urine collection or estimated creatinine clearance of greater than or equal to 50 mL/min. For creatinine clearance estimation , the Cockcroft and Gault equation should be used: * Male: Creatinine Clearance (CrCl) (mL/min) = (140 - age) times wt (kg)/ (serum creatinine times 72) * Female: Multiply above result by 0.85 * Urine protein/creatinine ratio (UPCR) less than or equal to 2 * Patient must be able to provide either archival tumor samples (haematoxylin and eosin (H\&E) slides and one paraffin block or 10 unstained slides) or undergo tumor biopsy. * Patient must be capable of understanding and complying with protocol requirements and is willing to give informed consent * The effects of XL184 on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of XL184 administration. Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s). \- Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea greater than or equal to 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason. EXCLUSION CRITERIA: * The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or nitrosoureas or mitomycin within 6 weeks before the first dose of study treatment. * Prior treatment with cabozantinib * Prior treatment with other small molecule inhibitors of Vascular Endothelial Growth Factor Receptors (VEGFR) within less than or equal to 2 years of study enrollment. * The subject has received radiation therapy: * to the thoracic cavity or gastrointestinal tract within 3 months before the first dose of study treatment * to bone or brain metastasis within 14 days before the first dose of study treatment * to any other site(s) within 28 days before the first dose of study treatment * The subject has received radionuclide treatment within 6 weeks before the first dose of study treatment * The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. * The subject has received any other type of investigational agent within 28 days before the first dose of study treatment. * The subject has not recovered to baseline or Common Terminology Criteria in Adverse Events (CTCAE). Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs. * The subject has a primary brain tumor * The subject has active brain metastases, leptomeningeal or epidural disease (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain scans are not required to confirm eligibility.) * The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test greater than or equal to 1.3 times the laboratory upper limit of normal (ULN) within 7 days before the first dose of study treatment. * The subject requires treatment, in therapeutic doses, with oral anticoagulants such as warfarin prior to initiation of protocol therapy. Low dose aspirin (less than or equal to 81 mg/day), lowdose warfarin (less than or equal to 1 mg/day), and low molecular weight heparin (LMWH) are permitted. Subjects will be permitted to use anticoagulation as described if treatment is required while they are enrolled on the protocol. * The subject requires chronic concomitant treatment of strong Cytochrome P450 3A4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the counter medicine or herbal product. * The subject has experienced any of the following within 3 months before the first dose of study treatment: * clinically-significant hematemesis or gastrointestinal bleeding * hemoptysis of greater than or equal to 0.5 teaspoon (greater than or equal to 2.5 mL) of red blood * any other signs indicative of pulmonary hemorrhage * The subject has tumor invading (or concern for invasion) major blood vessels * Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study. * The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. * The subject is unable to swallow tablets * The subject has a corrected Q wave, T wave (QT) interval calculated by the Fridericia formula (QTcF) \>500 ms within 28 days before treatment initiation. * The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation. * The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee. * The subject has had within 2 years before the start of study treatment evidence of another malignancy which required systemic treatment * Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the study agents. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.