Combining Radiosurgery and Nivolumab in the Treatment of Brain Metastases

Inclusion Criteria

• •1. Men and women, ≥ 18 years of age
• •2. Willing and able to give written informed consent
• •3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 28 days prior to registration
• •4. Radiation Therapy Oncology Group (RTOG) neurological function score of 0-1 within 28 days prior to registration
• •5. Histologic diagnosis of NSCLC, SCLC, Melanoma OR ccRCC
• •6. Stage IV cancer with brain metastases (Patients may have untreated primary disease)
• •7. Presenting with previously un-irradiated brain metastasis (10 cc maximum volume of brain disease based on the diagnostic screening MRI done within 28 days of registration))
• •8. Measurable/evaluable brain disease
• •9. Having received less than 4 lines of prior systemic treatments
• •10. Ability to be treated with either gamma knife or a linear accelerator based radiosurgery system
• •11. Ability to complete neurocognitive exams without assistance
• •12. Ability to complete QOL questionnaires with or without assistance
• •13. Screening laboratory values must meet the following criteria and should be obtained within 28 days prior to registration:
• •* White Blood Cell (WBC) ≥ 2000/uL
• •* Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• •* Platelets≥ 100 x 109/L
• •* Hemoglobin ≥ 90 g/L (may be transfused)
• •* Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN) or Creatinine Clearance ≥ 50 ml/min (calculated -cockcroft-Gault)
• •* Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤3 x ULN without liver metastasis,≤ 5 x ULN with liver metastases
• •* Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• •14. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (28 days plus the time required for Nivolumab to undergo five half-lives) after the last dose of investigational drug
• •15. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab
• •16. Women must not be breastfeeding
• •17. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of Nivolumab product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception).