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

Phase 1/Phase 2
18 Years
Not Enrolling
Recurrent Glioblastoma

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Trial Information

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

This is a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part is to
estimate the MTD and/or to identify the recommended phase II dose (RP2D) for the combination
of INC280 and buparlisib, followed by the phase II part to assess the clinical efficacy and
to further assess the safety of the combination. A maximum of 10 patients, who have received
bevacizumab treatment before entering the study, will be enrolled in the phase II part. In
addition, a surgical arm will start concurrently with the phase II part, to determine the
PK/PD profile of the study drug combination in patients undergoing tumor resection for
recurrent glioblastoma after 7 to 10-days treatment.

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

- 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%.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase II: Progression free survival rate (PFSR)

Outcome Description:

Estimate anti-tumor activity of INC280 in combiation with buparlisib in patients with recurrent glioblastoma.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

September 2013

Completion Date:

April 2015

Related Keywords:

  • Recurrent Glioblastoma
  • c-MET inhibitor
  • PI3K inhibitor
  • PTEN mutations
  • homozygous deletion of PTEN or PTEN negative by IHC
  • INC280
  • BKM120
  • buparlisib
  • Glioblastoma