Gemcitabine Hydrochloride, Cisplatin, and Ipilimumab as First-Line Therapy in Treating Patients With Metastatic Urothelial Cancer

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; note: HIPAA authorization may be included in the informed consent or obtained separately
• Karnofsky performance status (KPS) >= 80% within 7 days prior to registration for protocol therapy
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy 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; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as: amenorrhea >= 12 consecutive months without another cause, or for women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL; women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [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
• Females must not be pregnant or breastfeeding
• Histological or cytological proof of urothelial carcinoma of the urethra, bladder, ureters, or renal pelvis
• Advanced (clinical stage T4b, unresectable) or metastatic disease
• No active central nervous system (CNS) metastases; subjects with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis within 28 days of registration; note: a subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic
• 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; note: 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
• Prior radiation therapy is allowed to < 25% of the bone marrow; note: no radiation therapy within 30 days prior to registration for protocol therapy
• 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); note: patients with other immune disorders should not be enrolled without discussion with the principal investigator
• 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 adverse events (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 tumor necrosis factor receptor superfamily, member 9 (CD137) agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist
• No known active or chronic infection with human immunodeficiency virus (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 orally [PO] daily for > 6 months during the past year)
• White blood cell count (WBC) >= 3.5K/mm^3
• Hemoglobin (Hgb) >= 9 g/dL
• Platelets >= 100K/mm^3
• Absolute neutrophil count (ANC) >= 1.5K/mm^3
• Calculated creatinine clearance of >= 55 cc/min using the Cockcroft-Gault formula
• Bilirubin =< 1.5 times (x) upper limit of normal (ULN) (except patients with Gilbert’s syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• Aspartate aminotransferase (AST) =< 2.5 x ULN; note: if the patient has liver metastases present, then =< 5 x ULN
• Alanine aminotransferase (ALT) =< 2.5 x ULN; note: if the patient has liver metastases present, then =< 5 x ULN
• Patient must consent to mandatory correlative sample collection