Phase II Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Treating Patients With Stage IV Melanoma

PRIMARY OBJECTIVES:

I. To determine feasibility and immune-related clinical responses associated with SBRT when
given in conjunction with ipilimumab.

SECONDARY OBJECTIVES:

I. To determine late toxicity and immune pharmacodynamic changes after SBRT followed by
ipilimumab.

OUTLINE:

Patients undergo a total of 3 fractions of stereotactic body radiotherapy between days 1-13.
Patients then receive ipilimumab intravenously (IV) every 3 weeks. Treatment repeats every 3
weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 60 days, and then every
effort will be made to obtain records of patients during this follow up, and permission will
be sought for the investigators and/or study team to re-contact the patient directly with
regard to health status and toxicity.

Inclusion Criteria:

- Histologically confirmed diagnosis of melanoma

- Previously treated or previously untreated stage IV melanoma by American Joint
Committee on Cancer (AJCC) staging criteria

- Presence of an index lesion between 1 and 5 cm

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

- Signed informed consent document

- Adequate renal, hepatic, and hematologic indices for ipilimumab therapy

- Ability to tolerate stereotactic body radiation therapy (e.g. lie flat and hold
position for treatment)

Exclusion Criteria:

- Prior systemic therapy within 14 days of study enrollment; patients must be adequately
recovered from prior systemic therapy side effects as deemed by the treating
investigator

- Clinical contraindication to stereotactic body radiotherapy (e.g. active systemic
sclerosis, active inflammatory bowel disease if bowel is within target field, etc)

- Presence of central nervous system metastasis (including active brain metastasis);
active brain metastasis would be defined as untreated brain metastases; if the brain
metastases have received prior treatment (usually either with surgery or radiation),
they are no longer active

- Long-term use of systemic corticosteroids; patients with replacement steroids and not
immunosuppressive steroids may enroll in the study

- Prior radiation therapy (RT) that precludes the delivery of SBRT