First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma

Inclusion Criteria:

* Histological or cytological proof of urothelial carcinoma of the urethra, bladder, ureters, or renal pelvis.
* Advanced (clinical stage T4b, unresectable) or metastatic disease.
* Prior radiation therapy is allowed to \< 25% of the bone marrow.
* Age \> 18 years at the time of consent.
* Written informed consent and HIPAA authorization for release of personal health information.
* Females must not be pregnant or breastfeeding.
* WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.
* Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study \[and for up to 26 weeks after the last dose of investigational product\] in such a manner that the risk of pregnancy is minimized.
* Prior Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). Patients with other immune disorders should not be enrolled without discussion with the principal investigator.

Exclusion Criteria:

* No active CNS metastases. Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
* No prior malignancy is allowed except for cancers that have been definitively treated with a risk of recurrence of \< 30% based on the treating oncologists assessment.
* Patients may not have received prior systemic chemotherapy for metastatic/advanced urothelial carcinoma. Prior neoadjuvant/adjuvant therapy is permitted if completed ≥ 12 months prior to registration for protocol therapy. Prior intravesical therapy is permitted.
* No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
* No underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
* No non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
* No history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist.
* No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
* No clinically significant infections as judged by the treating investigator.
* No chronic systemic corticosteroids (defined as the equivalent of prednisone ≥ 20 mg PO daily for \> 6 months during the past year)