Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma

* INCLUSION CRITERIA:
* Patients must have a histologically confirmed diagnosis of metastatic, progressive urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.
* Patients must have progressive metastatic disease defined as new or progressive lesions on cross-sectional imaging.
* Patients must have at least:

  * One measurable site of disease (according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as more than or equal to 20 mm with conventional techniques or as less than or equal to 10 mm with spiral computed tomography (CT) scan.
  * Or, appearance of one new bone lesion
* Patients must have been previously treated with at least one prior cytotoxic chemotherapy regimen or agent. Patients may have received any number of prior cytotoxic agents.
* Archival tumor tissue must be available for enrollment.
* Tumor amenable to biopsy will be mandatory for this study.
* Age more than or equal to 18 years. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky more than or equal to 60%,).
* Patients must have normal organ and marrow function as defined below:

  * hemoglobin more than or equal to 9 g/dL
  * leukocytes more than or equal to 3,000/mcL
  * absolute neutrophil count more than or equal to 1,200/mcL
  * platelets more than or equal to 75,000/mcL
  * total bilirubin within normal institutional limits
  * Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT)/Serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 X institutional upper limit of normal
  * creatinine 1.5 x the normal institutional limits

OR

--creatinine clearance more than or equal to 40 mL/min/1.73 m\^2

* Because many of the therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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.
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy may be eligible if there are no pharmacokinetic interactions with the agents used on the study, stable on Chimeric antigen receptor T-cell (CART) therapy and cluster of differentiation 4 (CD4) is \>200 and viral load is undetectable.
* Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

* The patient has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks or biologic agents (e.g., cytokines or antibodies) within 4 weeks prior to study enrollment.
* Patients who are receiving any investigational agents.
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with brain metastases that are stable after more than or equal to 1 year after primary surgery or radiation will not be excluded.
* The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) less than or equal to Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs(.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients who are Hepatitis B or C positive.
* Pregnant women are excluded from this study because the agents used in the study have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated with these agents. These potential risks may also apply to other agents used in this study.