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

Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Brain/Neuro Cancer: Recurrent Glioblastoma
NCT ID: NCT01870726 (View complete trial on
DFCI Protocol ID: 13-501


The study will assess the safety and the dose of the combination of INC280 and buparlisib (BKM120), as well as the anti-tumor activity of the combination, in patients with recurrent glioblastoma with PTEN mutations, homozygous deletion of PTEN or PTEN negative by IHC. In addition, the anti-tumor activity of INC280 single agent will be assessed in patients with recurrent glioblastoma with c-Met alteration.


Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Patrick Wen, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
Jorg Dietrich, M.D., Massachusetts General Hospital

Dana-Farber Cancer Institute: Lisa Doherty,
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - ≥ 18 years of age. - Histologically confirmed diagnosis of glioblastoma after initial tumor resection with radiographic evidence of recurrent tumor per RANO criteria. - Documented evidence of PTEN mutations, homozygous deletion of PTEN or PTEN negative by IHC confirmed by local or central assessment - Must have received the following treatment for glioblastoma: - Prior adjuvant treatment with radiotherapy and temozolomide; - A maximum of two prior chemotherapy regimens (including bevacizumab or other direct VEFG/VEGFR inhibitors) for recurrent disease are permitted. - Representative archival or newly obtained 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 - Received radiation (including therapeutic radioisotopes such as strontium 89) therapy ≤ 4 weeks 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. - Currently being treated with Enzyme Inducing Anti-Epileptic Drug (EIAED). If previously on an EIAED, the patient must be off of it for at least 2 weeks prior to study treatment. - Currently receiving warfarin or other coumadin-derived anticoagulants for treatment, prophylaxis or otherwise. - Currently receiving increasing or chronic treatment ( > 5 days) with corticosteroids 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 ≥2 x upper limit of normal (ULN) - Serum creatinine >1.5 x ULN or creatinine clearance ≤ 45 mL/min - Alanine aminotransferase (AST) or aspartate aminotransferase (ALT) > normal range (or < 3.0 x ULN if liver metastases are present) - Fasting plasma glucose > 120mg/dL or > 6.7 mmol/L - HbA1c > 8%.
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