A Phase Ib/II, Multi-center, Open-label Study of Single-agent INC280 in Combination With Buparlisib in Patients With Recurrent Glioblastoma
- ≥ 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.
- 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
- 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
- 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
- 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%.