Trial of SBRT With Concurrent Ipilimumab in Metastatic Melanoma

The safety profiles of ipilimumab and SBRT are well studied separately 22-24, but prospective data on the combination of ipilimumab and high-dose SBRT are lacking. Consequently, the first goal of the proposed prospective phase I trial is to assess the safety (dose limiting toxicity, DLT) of the combination of high-dose SBRT and ipilimumab in patients with advanced melanoma.

Inclusion criteria

• Signed informed consent and willingness to comply to the treatment and follow-up
• Histological diagnosis of melanoma,
• at least 3 extracranial measurable metastatic lesions per RECIST 1.1,
• Karnofsky Performance score >60,
• Age ≥18,
• Life expectancy ≥ 16 weeks
• Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment. Men and women should agree to use effective contraception, during the study and for 1 month following the last dose of investigational product.
• ≥ 28 days between last treatment with standard or experimental chemotherapy, surgery, radiotherapy, cytokine therapy or immunotherapy. Patient should be completely recuperated of any clinical toxicity developed during previous treatments.
• Patients should have adequate organ function for ipilimumab treatment

Exclusion criteria

• Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants.
• Prior malignancy: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
• Prior radiotherapy preventing treatment with SBRT.
• Disorder precluding understanding of trial information.
• Autoimmune disease: Patients with a history of 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.
• Known Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C.
• 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 (used in the management of cancer or non-cancer-related illnesses).
• Pregnant women
• Breast feeding
• History of or current immunodeficiency disease or prior treatment compromising immune function, prior allogeneic stem cell transplantation.