Stereotactic Radiosurgery Timing with Immunotherapy in Patients with Brain Metastases from Non-Small Cell Lung Cancer, STICk-IM Trial

Inclusion Criteria

• Patients must have 1 to 15 newly diagnosed brain metastases, =< 3 cm in the largest dimension, with at least one metastasis measuring >= 0.5 cm
• Primary tumor histology must be one confirmed as one of the following: * Squamous non-small cell lung cancer (NSCLC) * Adenocarcinoma NSCLC * Not otherwise specified NSCLC
• Patient must be able and willing to undergo a thin cut magnetic resonance imaging (MRI) at Duke, which is required for study entry
• Patient must be planned for immunotherapy treatment as their next systemic therapy, including monotherapy or in combination with chemotherapy
• Patients previously treated with a tyrosine kinase inhibitor (TKI) may be eligible, if a second line (or later) immunotherapy regimen is planned
• Patients must be asymptomatic or minimally symptomatic, requiring the equivalent of =< 2 mg dexamethasone/day for at least 7 days prior to enrollment
• Female and male subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in the Duke Contraception Policy
• Age >= 18 years of age at the time of entry into the study
• Karnofsky performance score (KPS) >= 70
• Prothrombin and partial thromboplastin times =< 1.2 x upper limit of normal
• Neutrophil count >= 1000
• Hemoglobin >= 9 g/dl
• Platelet count >= 100,000/ul
• Creatinine=< 1.2 x upper limit of normal range
• A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study

Exclusion Criteria

• Patients on the equivalent of > 2 mg of dexamethasone daily =< 7 days before receiving study treatment
• Patients who have previously receive whole brain radiation therapy (WBRT)
• Patients must not have ever received immunotherapy in the stage IV setting. Prior immune therapy as part of treatment for stage I-III disease is allowed assuming an interval > 6 months has passed from the completion of that therapy
• Patients with leptomeningeal disease. However, patients with discrete dural-based lesions may be eligible
• Females who are pregnant or breast-feeding
• Patients with an impending, life-threatening cerebral hemorrhage or herniation, based on the assessment from a brain MRI of the study neurosurgeons or their designate
• Patients with severe, active co-morbidity, defined as follows: * Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5 degree Fahrenheit [F]/37.5 degree Celsius [C]) * Patients with known immunosuppressive disease or known uncontrolled human immunodeficiency virus infection * Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association class 3 or 4)
• Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used
• Patients with prior, unrelated malignancy requiring current active treatment in the last 3 years with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• Patients with a known history of hypersensitivity to the physician’s choice of immune checkpoint inhibitor, or any components of the inhibitor
• Patients who have any contraindications to immunotherapy
• Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
• History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral computed tomography (CT) scan