Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy

Inclusion Criteria

• Signed Written Informed Consent

Before any study procedures are performed, subjects (or their legally acceptable representatives) will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel.

• Target Population
• Histologically confirmed Stage IV melanoma.
• Must have failed at least one systemic therapy for malignant melanoma or be intolerant to at least one prior systemic treatment.
• Subjects with asymptomatic brain metastases are eligible. (Systemic steroids should be avoided if possible, or the subject should be stable on the lowest clinically effective dose, as steroids as they may interfere with the activity of ipilimumab if administered at the time of the first ipilimumab dose.)
• Primary ocular and mucosal melanomas are allowed.
• Must be at least 28 days since treatment with chemotherapy, biochemotherapy, surgery, radiation, or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy of ≥ 16 weeks.
• Subjects must have baseline (screening/baseline) radiographic images, (e.g. brain, chest, abdomen, pelvis, and bone scans with specific imaging tests to be determined by the attending physician) within 6 weeks of initiation of ipilimumab.
• Required values for initial laboratory tests:
• White blood cell (WBC) ≥ 2000/uL (~ 2 x 10^9/L)
• Absolute neutrophil count (ANC) ≥ 1000/uL (~ 1 x 10^9/L)
• Platelets ≥ 75 x 10^3/uL (~ 75 x 10^9/L)
• Hemoglobin ≥ 9 g/dL (~ 80 g/L; may be transfused)
• Creatinine ~ 2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ~ 2.5 x ULN for subjects without liver metastasis ~ 5 times for liver metastases
• Bilirubin: ~ 2.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of 35 mIU/mL
• Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product.

c) Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria

• Sex and Reproductive Status
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 8 weeks after the last dose of investigational product.
• WOCBP using a prohibited contraceptive method.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or before investigational product administration.
• Target Disease Exceptions
• Subjects on any other systemic therapy for cancer, including any other experimental treatment.
• Prior treatment with an anti-CTLA-4 antibody if treatment failure was due to adverse events (AEs). If a subject was discontinued from the prior anti-CTLA-4 treatment due to an AE or serious adverse event (SAE), regardless of the type of event, that discontinuation constitutes an exclusion criterion. If AEs were serious enough to require a subject's withdrawal from prior treatment, the subject should be excluded from this study.
• A history of AEs with prior IL-2 or Interferon wi