Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma

Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of lung adenocarcinoma that demonstrates ALK rearrangement as detected by the approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana IHC test. Evidence of rearrangement by gene sequencing tests such as FoundationOne or Caris will also be seen as evidence of ALK abnormality and meeting eligibility requirement. 2. Patients with no prior ALK-inhibitor therapy will be placed in cohort A, those treated with one prior line of ALK-inhibitor (at any time) will enter cohort B. 3. Patients will not have any other curative therapeutic option, such as radiation or surgery. 4. WHO performance status 0-2. 5. Age ≥18 years. 6. Patients must have recovered from all toxicities related to any prior anticancer therapies to ≤ Grade 2 (CTCAE v 4.03), provided that any concomitant medication is given prior to initiation of treatment with ceritinib. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment. 7. Adequate organ function: the following laboratory criteria have been met: * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Hemoglobin (Hgb) ≥ 8 g/dL * Platelets ≥ 75 x 109/L * Serum creatinine \<1.5 mg/dL and /or calculated creatinine clearance (using Cockcroft-Gault formula) ≥30 mL/min * Total bilirubin ≤ 1.5 x upper limit of normal (ULN), except for patients with Gilbert's syndrome who may be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN * Aspartate transaminase (AST) \< 2.0 x ULN, except for patients with liver metastasis, who are only included if AST \< 3 x ULN; alanine transaminase (ALT) \< 2.0 x ULN, except for patients with liver metastasis, who are only included if ALT \< 3 x ULN * Alkaline phosphatase (ALP) ≤5.0 x ULN * Fasting plasma glucose ≤175 mg/dL (≤9.8 mmol/L) * Serum amylase ≤ 2 x ULN * Serum lipase ≤ ULN 8. Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits before the first dose of ceritinib: * Potassium * Magnesium * Phosphorus * Total calcium (corrected for serum albumin) 9. Written informed consent for the protocol must be obtained prior to any screening procedures. 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures. Exclusion Criteria: 1. Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate). 2. History of carcinomatous meningitis. 3. Prior therapy with ceritinib. 4. Presence or history of a malignant disease other than lung adenocarcinoma that has been diagnosed and/or required therapy within the past year and is undergoing active anticancer treatment. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type. 5. Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention). 6. Patient who has received thoracic radiotherapy to lung fields ≤4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy ≤2 weeks prior to starting the study treatment or has not recovered from radiotherapy-related toxicities. Palliative radiotherapy for bone lesions ≤2 weeks prior to starting study treatment is allowed. 7. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as: * unstable angina within 6 months prior to screening; * myocardial infarction within 6 months prior to screening; * history of documented congestive heart failure (New York Heart Association functional classification III-IV); * uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication * initiation or adjustment of antihypertensive medication(s) is allowed prior to screening; * ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication; * other cardiac arrhythmia not controlled with medication; * Corrected QT (QTcF) \>470 ms using Fridericia's correction on the screening ECG 8. Impaired GI function or GI disease that may alter absorption of ceritinib or inability to swallow up to five ceritinib capsules daily. Although, patients unable to swallow capsules will be allowed to participate in this study, by following the specific instructions on making a slurry of the medication. 9. Patient has impairment of GI function or GI disease that may significantly alter the absorption of ceritinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). 10. Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of participation (see Appendix 1 Tables): * Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm) * Strong inhibitors or strong inducers of CYP3A4/5 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org) * Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org) * Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed (eg, dabigatran, rivaroxaban, apixaban). * Unstable or increasing doses of corticosteroids; If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms (non-CNS), dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment. * Enzyme-inducing anticonvulsive agents * Herbal supplements 11. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and agree to continue for 3 months after the last dose of study treatment. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. * Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. For female subjects on the study the vasectomized male partner should be the sole partner for that subject. * Combination of any two of the following (a+b or a+c or b+c): 1. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception. 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. 13. Sexually active males unless they agree to use a condom during intercourse while taking drug and agree to continue for 3 months after the last dose of study treatment. Male patients for 3 months should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. 14. Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease. 15. Patient has other severe, acute, or chronic medical conditions including uncontrolled diabetes mellitus or psychiatric conditions or laboratory abnormalities that, in the opinion of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results. 16. Patient has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks prior to starting study treatment or has not recovered from side effects of such procedure. Video-assisted thoracic surgery (VATS) and mediastinoscopy will not be counted as major surgery and patients can receive study treatment ≥1 week after these procedures.