Safety and Efficacy of INC280 and Buparlisib (BKM120) in Patients With Recurrent Glioblastoma

Inclusion Criteria: * ≥ 18 years of age. * Histologically confirmed diagnosis of glioblastoma (after initial tumor resection or biopsy) with radiographic evidence of recurrent tumor per RANO criteria. * Phase Ib: Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score \<10) by IHC confirmed by local or central assessment. * Phase II: Documented evidence of c-Met amplification (GCN\>5) (fusion transcripts or mutant c-Met may be eligible after discussion with Novartis) or PTEN mutations, homozygous deletion of PTEN or PTEN negative (H Score \<10) by central assessment. * Must have received the following treatment for glioblastoma: •Prior treatment with radiotherapy and temozolomide; Note: A maximum of two prior chemotherapy/antibody regimens (including bevacizumab or other direct VEFG/VEGFR inhibitors) for recurrent disease are permitted. * Representative archival tumor sample from glioblastoma (formalin-fixed paraffine embedded tissue) must be available. * ECOG performance status ≤ 2. * Able to swallow and retain oral medication. * Patients in the surgical arm only: patients with recurrent glioblastoma must be eligible for surgical resection as deemed by the site Investigator. Exclusion Criteria: * Prior or current treatment with a c-MET inhibitor or HGF-targeting therapy * Prior treatment with a PI3K and/or mTOR inhibitors for glioblastoma or for pre-existing neoplasm transformed to glioblastoma (applicable for combination treatment arm only) * Received radiation (including therapeutic radioisotopes such as strontium 89) therapy ≤ 3 months prior to the first dose of study treatment and have not recovered from side effects of such therapy (≤ Grade 1) prior to the first dose of study treatment, except for alopecia. * Receiving treatment with medications that are known strong inhibitors or inducers of CYP3A, and cannot be discontinued 7 days prior to the start of the treatment and during the course of the study. * Receiving treatment with medications that are known CYP3A, CYP1A2, CYP2C8, CYP2C9 or CYP2C19 substrates with narrow therapeutic index, and cannot be discontinued during the course of the study. * Receiving treatment with long acting proton pump inhibitors, and cannot be discontinued 3 days prior to the start of INC280 treatment and during the course of the study. * Currently receiving warfarin or other coumadin-derived anticoagulants for treatment, prophylaxis or otherwise. * Currently receiving increasing or chronic treatment ( \> 5 days) with corticosteroids (e.g. dexamethasone \> 4 mg/day or other corticosteroids equivalent dose) or another immunosuppressive agent. * History of acute or chronic pancreatitis or any risk factors that may increase the risk of pancreatitis. * Active cardiac disease or a history of cardiac dysfunction. * Impairment of gastrointestinal (GI) function or GI disease that might significantly alter the absorption of study drug * Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM- IV). * Anxiety ≥ CTCAE grade 3 * Any of the following baseline laboratory values: * Hemoglobin \< 9 g/dL * Platelet count \< 75 x 109/L * Absolute neutrophil count (ANC) \< 1.0 x 109/L * INR \> 1.5 * Serum lipase \> normal limits for the institution * Asymptomatic serum amylase \> grade 2 * Potassium, magnesium, and calcium (corrected for albumin) \> normal limits for the institution * Total bilirubin \> 1.5 x ULN * Serum creatinine \>1.5 x ULN or creatinine clearance ≤ 45 mL/min * Alanine aminotransferase (AST) or aspartate aminotransferase (ALT) \> 3.0 x ULN (or \< 5.0 x ULN if liver metastases are present) * Fasting plasma glucose \> 120mg/dL or \> 6.7 mmol/L * HbA1c \> 8%.