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.