Alectinib Alone or in Combination with Stereotactic Radiosurgery for Controlling Disease in Patients with Stage IV Non-small Cell Lung Cancer and Brain Metastases

Inclusion Criteria

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Age ≥ 18 years at the time of consent
• First language must be English
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 within 14 days prior to registration
• Histological or cytological confirmation of stage IV (per American Joint Committee on Cancer [AJCC] 8th edition) non-small cell lung cancer (NSCLC)
• At least one intracranial metastasis on MRI imaging
• Confirmation of positive ALK rearrangement per local testing per standard of care testing
• All subjects must have brain metastases and be either asymptomatic or minimally symptomatic per investigator discretion without plan for surgical intervention within 28 days of study start. Patients with neurological symptoms that are controlled with dose of corticosteroids or anti-epileptic medications are eligible. Patients with asymptomatic leptomeningeal disease may be eligible for trial providing they meet all other eligibility criteria
• Subjects must be planning on therapy with alectinib. Alectinib may have been started up to 6 weeks prior to radiation
• Prior non-ALK directed therapy for metastatic disease is permitted. Patients who have received prior neoadjuvant, adjuvant chemotherapy, radiotherapy, immunotherapy (PD-1 or PD-L1 monoclonal antibodies) or chemoradiotherapy with curative intent for nonmetastatic disease must have experienced a treatment-free interval of at least 3 months from registration since the last chemotherapy, radiotherapy, immunotherapy, or chemoradiotherapy cycle
• Documentation of consultation with a radiation oncologist confirming agreement to delay radiation therapy
• Absolute neutrophil count (ANC) ≥ 1.0 K/mm^3 (obtained within 14 days prior to registration)
• Hemoglobin (Hgb) ≥ 9.0 g/dL (obtained within 14 days prior to registration)
• Estimated glomerular filtration rate ≥ 45 mL/min/1.73 m^2 (obtained within 14 days prior to registration) * Estimated glomerular filtration rate calculated using the Modification of Diet in Renal Disease equation
• Bilirubin ≤ 1.5 × upper limit of normal (ULN) (obtained within 14 days prior to registration)
• Aspartate aminotransferase (AST) ≤ 3 × ULN (obtained within 14 days prior to registration) * ≤ 5 x ULN for patients with concurrent liver metastasis
• Alanine aminotransferase (ALT) ≤ 3 × ULN (obtained within 14 days prior to registration) * ≤ 5 x ULN for patients with concurrent liver metastasis
• Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration
• Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
• Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria

• Active infection requiring systemic therapy
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial
• Treatment with any investigational drug within 28 days prior to registration
• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer
• Acute viral, autoimmune, alcoholic, or other types of acute hepatitis