Stereotactic Radiosurgery and Immune Checkpoint Inhibitors With NovoTTF-200M for the Treatment of Melanoma Brain Metastases

PRIMARY OBJECTIVE: I. To determine the safety of combining tumor treating fields therapy (TTFields) to the two therapeutic backbones (stereotactic radiosurgery \[SRS\]+pembrolizumab and SRS+dual-checkpoint). SECONDARY OBJECTIVES: I. To evaluate skin toxicity (grade 1 \& 2 skin \> 20% and grade 3 \& 4 toxicity above 2% at 4-6 weeks and 3 months). (Skin AES include Dermatitis, Erosions, Infections, Ulceration). II. Control of the treated lesion in the brain with SRS+ immune checkpoint inhibitors (ICI) (i.e. local control), development of additional sites of disease in the brain that were not initially treated with SRS (i.e. anywhere intra-cranial failure), intra-cranial progression free survival (local control of the area that received SRS and anywhere intra-cranial failure), extra-cranial disease response (overall progression free survival), and overall survival. III. To evaluate treatment response at un-irradiated and extra-cranial sites (i.e. the abscopal effect) with all three arms. IV. To compare differences in potential serological and immune biomarkers, pretreatment, during treatment, and post treatment. V. Symptomatic radionecrosis rates at 3 and 6 months. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients receive standard of care pembrolizumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive standard of care nivolumab and ipilimumab and undergo 3-5 fractions SRS. Patients also undergo TTFields over 8 hours daily using NovoTTF-100M device until intra-cranial progression or until end of immunotherapy treatments at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 28 days.