Gemcitabine Hydrochloride, Cisplatin, and Nivolumab in Treating Patients with Muscle-Invasive Bladder Cancer

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration * NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 28 days prior to registration
• Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder (i.e., ct2-4n0m0) candidate for cystectomy as per treating physician
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained within 28 days prior to registration)
• Hemoglobin (Hgb) >= 9 g/dL (obtained within 28 days prior to registration)
• Platelets >= 100 x 10^9/L (obtained within 28 days prior to registration)
• Creatinine =< 1.5 or creatinine clearance >= 60 mL/min (obtained within 28 days prior to registration) * Cockcroft-Gault formula will be used to calculate creatinine clearance
• Bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (obtained within 28 days prior to registration)
• Aspartate aminotransferase (AST) =< 3 x ULN (obtained within 28 days prior to registration)
• Alanine aminotransferase (ALT) =< 3 x ULN (obtained within 28 days prior to registration)
• All subjects must have adequate archival tissue identified during screening (i.e., at least 15 unstained slides or paraffin block). Subjects without available archival tissue must be discussed with the sponsor-investigator
• Women of childbearing potential must have a negative serum or urine pregnancy within 7 days prior to cycle 1 day 1 (C1D1) * NOTE: “Women of childbearing potential” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL * NOTE: Women of childbearing potential (WOCBP) receiving nivolumab must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent to 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent to 7 months after the last dose of investigational product. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Men will not be required to use contraception * HIGHLY EFFECTIVE METHODS OF CONTRACEPTION: ** Male condoms with spermicide ** Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subject’s WOCBP partner. Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug ** Nonhormonal IUDs, such as ParaGard ** Tubal ligation ** Vasectomy ** Complete Abstinence which is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence * LESS EFFECTIVE METHODS OF CONTRACEPTION: ** Diaphragm with spermicide ** Cervical cap with spermicide ** Vaginal sponge ** Male Condom without spermicide ** Female Condom. A male and female condom must not be used together ** Progestin only pills by WOCBP subject

Exclusion Criteria

• No prior systemic chemotherapy for muscle-invasive urothelial cancer of the bladder
• Active infection requiring systemic therapy
• Pregnant or breastfeeding * NOTE: breast milk cannot be stored for future use while the mother is being treated on study
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Grade >= 2 neuropathy (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4)
• Prior radiation therapy for bladder cancer
• Known history of positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection. Testing not required
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Testing not required
• Evidence of interstitial lung disease or active, non-infectious pneumonitis
• Solid organ or allogeneic stem cell transplant