Ipilimumab and Stereotactic Body Radiation Therapy (SBRT) in Advanced Solid Tumors

• 1. Patients must have histological confirmation of metastatic cancer with at least one metastatic or primary lesion in the liver, lung, or adrenal gland. 2. Patients who have completed previous systemic therapies 5 drug half-lives or 4-weeks prior to enrollment on study, whichever is shorter. Note: patients with anaplastic thyroid will be waived from this inclusion criteria given the rapid trajectory of their disease. 3. All patients must have at least one metastatic or primary lesion within the lung or liver located in an anatomical location amenable to SBRT treatment with 50 Gy in 4 fractions, or if not, with either a lung, liver, or adrenal lesion treatable to 60 Gy in 10 fractions. 4. Repeat radiation in fields previously radiated will be allowed at the discretion of the treating physician. 5. Age \>/= 18 years 6. ECOG performance status \</=2 (Karnofsky \>60%). 7. Patients must have normal organ and marrow function as defined below: \
• Total bilirubin \</= 2.0 mg/dL. (Does NOT apply to patients with Gilbert's Syndrome) \
• Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) \<2.5 X institutional upper limit of normal (patients with liver involvement will be allowed \</= 5.0 X institutional upper normal limit) \*WBC \>/= 2500/uL, ANC \>/= 1000/uL \*Platelets \>/= 75K \*Hemoglobin \>/= 9g/dL \*Creatinine \</= 2.0 x ULN 8. Patients must be willing and able to review, understand, and provide written consent before starting therapy. 9. Patients with brain metastasis will be included as long as they are free of neurologic symptoms related to metastatic brain lesions and who do not require or receive systemic corticosteroid therapy in the 14 days prior to beginning ipilimumab therapy 10. Patients that have previously progressed on immunotherapy such as ipilimumab will be eligible.

1. Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus or autoimmune vasculitis \[e.g., Wegener's Granulomatosis\] are excluded from this study. 2. Active diverticulitis, intra-abdominal abscess, Gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation. 3. Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of Adverse Events: (AE's) e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies. 4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 5. Known active HIV, Hepatitis B, or Hepatitis C that has not been documented to be cured. 6. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab). 7. Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids while receiving ipilimumab (as long as steroid replacement is significantly greater than what is required for physiologic replacement, i.e. in hypothyroidism). 8. Pregnant women are excluded from this study. Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Acceptable forms of birth control include: Birth control pills plus a barrier method, such as a condom or diaphragm, Intrauterine devices (IUD) plus a barrier method, Implantable or injectable birth control (such as NorplantR or epo-ProveraR) started at least 3 months before joining the study, plus a barrier method, or Double-barrier method, such as a condom when used in combination with a diaphragm. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician. 9. History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician. 10. Prior allogeneic stem cell transplantation