Preoperative Ceritinib (LDK378) in Glioblastoma Multiforme and CNS Metastasis

Inclusion Criteria:

* One prior resection of GBM or MRI evidence of solid tumor CNS metastasis
* All GBM and NSLC metastases must be ALK+
* Eastern Cooperative Oncology Group performance status ≤2
* Archival tumor tissue block available for research use
* Ability to understand written informed consent
* Recovery from toxicities related to prior anticancer therapies to ≤ grade 2 (CTCAE v 4.03). Exception: patients with any grade alopecia
* The following lab criteria are met:

  * Absolute neutrophil count ≥ 1.5 x 10(9th power)/L
  * Hemoglobin ≥ 8 g/dL
  * Platelets ≥ 75 x 10(9th power)/L
  * Serum 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 and direct bilirubin ≤ 1.5 x ULN
  * Aspartate transaminase (AST) \< 3.0 x ULN, except for patients with liver metastasis, who are only included if AST \< 5 x ULN; alanine transaminase (ALT) \< 3.0 x ULN, except for patients with liver metastasis, who are only included if ALT \< 5 x ULN
  * Creatinine clearance ≥ 30 mL/min
* Patient has following lab values or has lab values corrected with supplements to be within normal limits at screening:

  * Potassium ≥ LLN
  * Magnesium ≥ LLN
  * Phosphorus ≥ LLN
  * Total calcium (corrected for serum albumin) ≥ LLN

Exclusion Criteria:

* Co-morbid condition(s) that prevent safe surgical treatment
* Active infection or fever \> 38.5°C
* Patients with known hypersensitivity to any excipients of ceritinib
* Prior therapy with ceritinib
* Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (affecting activities of daily living or requiring therapeutic intervention)
* Clinically significant uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:

  * history of documented congestive heart failure (New York Heart Association functional classification III-IV);
  * uncontrolled hypertension defined by a Systolic Blood Pressure ≥ 160 mm Hg and/or Diastolic Blood Pressure ≥ 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 QTc \> 450 msec using Fridericia correction on the screening ECG
* Impaired GI function or GI disease that may alter absorption of ceritinib or inability to swallow up to five ceritinib capsules daily
* Ongoing GI adverse events \> grade 2 (e.g. nausea, vomiting, or diarrhea) at the start of the study
* Receiving medications that meet 1 of the following criteria and cannot be discontinued at least 1 week prior to start of treatment with ceritinib and for the duration of participation:

  * Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes
  * Strong inhibitors or strong inducers of CYP3A4/5
  * Medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, CYP2C8 and/or CYP2C9
  * Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived anti-coagulant. Anticoagulants not derived from warfarin are allowed
* Pregnant or nursing (lactating) women.
* Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment.