Phase II Trial of Gemcitabine, Cisplatin, Plus Ipilimumab as First-line Treatment for Patients With Metastatic Urothelial Carcinoma: Hoosier Oncology Group GU10-148

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)