Concurrent Ipilimumab and Stereotactic Ablative Radiation Therapy (SART) for Oligometastatic But Unresectable Melanoma

Inclusion Criteria:

* Stage III or IV melanoma (AJCC 6th edition) with 5 or less metastatic sites that are not amenable to curative surgical resection, but can be adequately delineated for SART
* All sites of metastatic disease acceptable except brain-only and eye metastases, provided SART can be safely delivered to the site.
* Up to 2 prior systemic treatments for metastatic disease.
* Mucosal or ocular melanoma is allowed.
* Radiotherapy consultation and insurance preapproval for SART prior to enrollment.
* CT or MRI within 28 days of enrollment showing no evidence of brain metastases. Brain metastases allowed if stable by scans for ≥ 28 days following treatment.
* CT, PET/CT or MRI scan of chest, abdomen, pelvis (and soft tissue as indicated); bone scan (as indicated); and photographs of skin lesions (if applicable) within 28 days of enrollment.
* Hematology, liver function and renal function lab tests within required parameters.
* Recovered from all prior surgery and/or adjuvant treatment.
* No active or chronic infection with HIV, Hepatitis B or Hepatitis C.
* ECOG Performance Status 0 or 1.
* Men and women ≥ 18 years old.
* Men/Women of childbearing potential must use adequate contraception.

Exclusion Criteria:

* Untreated or uncontrolled brain metastases.
* Prior treatment with CTLA-4 agent, PD-1 or PD-1 ligand mAb or inhibitor for metastatic disease or as adjuvant therapy (or participation in blinded study).
* History of melanoma-associated retinopathy.
* History of other active malignancy within last 2 years, except adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma in situ of cervix, unless disease-free for 2 years.
* Autoimmune disease (vitiligo is not a basis for exclusion).
* History of clinically active diverticulitis (diverticulosis is not exclusion criterion per se).
* Serious uncontrolled medical disorder or active infection that would impede treatment.
* Underlying medical or psychiatric condition that would cause administration of ipilimumab to be hazardous, or would obscure interpretation of AEs.
* Any non-oncology vaccine therapy up to 1 month before or after any dose of ipilimumab.
* Concomitant therapy with IL-2, interferon, other non-study immunotherapy, or cytotoxic chemotherapy; immune-suppressive agents within 30 days of registration; other investigational therapies; chronic use of systemic corticosteroids (however, a low stable dose steroid for mild brain edema or adrenal insufficiency is allowed; topical and inhaled standard dose corticosteroids are allowed).
* Dementia or significantly altered mental status that would prohibit understanding or rendering of informed consent and compliance with protocol requirements.
* Pregnant or breastfeeding women.
* Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g. infectious) illness.