Radium Ra 223 Dichloride and Atezolizumab in Treating Patients with Bladder Cancer That Has Spread to the Bone

Inclusion Criteria

• Subjects must have a histologic diagnosis of urothelial carcinoma with radiologic, histologic or cytologic evidence of metastatic disease
• Subjects must have at least 1 bone metastasis of any size on imaging
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Subjects must have progression of disease within 12 months of platinum-containing chemotherapy (chemotherapy could have been given in the neoadjuvant, adjuvant or metastatic settings) for urothelial cancer
• Absolute neutrophil count >= 1500/uL
• White blood cell count > 2500/uL
• Lymphocyte count >= 300/uL
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 10.0 g/dl
• Total bilirubin < 2.5 x upper limit of institutional normal reference range; patients with known Gilbert disease who have serum bilirubin =< 3 x upper limit of normal (ULN) may be enrolled
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 2.5 x upper limit of institutional normal reference range
• Serum creatinine < 3.0 mg/dl or if elevated, a calculated glomerular filtration rate (GFR) of > 30 mL/min/1.73 m^2
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN; this applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose
• Albumin > 25 g/L
• Subjects must have measurable disease on physical exam or imaging per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.03 from toxicities related to any prior treatments, unless adverse events (AE[s]) are clinically non-significant and/or stable on supportive therapy
• Patients must be >= 2 weeks from most recent systemic therapy or radiation therapy
• Women of childbearing potential must have a negative serum pregnancy test within 28 days prior to registration; women of non-childbearing potential are defined as those who have no uterus, ligation of the fallopian tubes, are naturally postmenopausal for at least 12 consecutive months or have undergone surgical removal of the ovaries
• Female subjects of childbearing potential and their male partners, and male subjects must be willing to use a highly effective method of contraception from the time consent is signed until 6 months after treatment discontinuation; highly effective forms of contraception include complete sexual abstinence or use of a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year; barrier methods (ex: condom) used alone, periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
• Ability to understand and the willingness to sign a written informed consent
• Life expectancy >= 12 weeks
• Able to comply with study protocol, in the investigator’s judgment

Exclusion Criteria

• Prior treatment with anti-PD-1/PD-L1, and anti-CTLA-4 is NOT allowed; prior intravesical Bacillus Calmette–Guérin (BCG) therapy is allowed
• Treatment with any investigational agent or on an interventional clinical trial within 30 days prior to treatment on protocol
• No prior or concurrent malignancy is allowed except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years
• Autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus; Note: vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed
• Need for systemic corticosteroids > 10 mg prednisone daily or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate); use of topical and inhaled corticosteroids is permitted
• Any history of allografts
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (class II or greater), myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, or unstable angina; patients with known left ventricular ejection fraction (LVEF) < 40% will be excluded; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50%, must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
• Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 14 days prior to initiation of study treatment; patients receiving prophylactic antibiotics (e.g. for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• Major surgical procedure within 4 weeks prior to initiation of study treatment of anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenetic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Positive test for human immunodeficiency virus (HIV)
• Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C; patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible; patients positive for hepatitis c virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
• Active tuberculosis
• Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment with atezolizumab or anticipation that such a live, attenuated vaccine will be required during the study; influenza vaccination should be given during influenza season only (approximately October to May in the Northern Hemisphere); patients must agree not to receive live attenuated influenza vaccine (e.g., FluMist) within 28 days prior to study treatment, during treatment, or within 90 days following the last dose of atezolizumab
• Bone marrow dysplasia