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

Stopped early · Phase 1/Phase 2

Conditions studied: c-MET Inhibitor; PI3K Inhibitor, PTEN Mutations, Homozygous Del. of PTEN or PTEN Neg. by IHC, c-Met Ampli. by FISH, INC280, BKM120, Buparlisib; Recurrent GBM

In brief

The study assessed 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 should have been assessed in patients with recurrent glioblastoma with c-Met alteration.

Key facts

Study ID

NCT01870726

Run by

Novartis Pharmaceuticals

People needed

43

Starts

2014-01-09

Expected to finish

2016-12-23

Last updated by the study team

2018-05-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• ≥ 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.

You may not qualify if…

• 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

Where it is running

• Dana Farber Cancer Institute SC — Boston, Massachusetts, United States
• Columbia University Medical Center- New York Presbyterian Dept of Oncology — New York, New York, United States
• Memorial Sloan Kettering Cancer Center Neurology — New York, New York, United States
• Duke University Medical Center Duke - Baker — Durham, North Carolina, United States
• University of Texas MD Anderson Cancer Center SC-3 — Houston, Texas, United States
• Novartis Investigative Site — Bonn, Germany
• Novartis Investigative Site — Heidelberg, Germany
• Novartis Investigative Site — Tübingen, Germany
• ErasmusMC Cancer Institute - Neurooncology, RM G3-55 — Rotterdam, Netherlands
• University Medical Center Utrecht, Rm Q05.4.300, P.O. Box 85500 — Utrecht, Netherlands
• Novartis Investigative Site — Barcelona, Catalonia, Spain
• Novartis Investigative Site — Madrid, Spain
• Novartis Investigative Site — Sankt Gallen, Switzerland

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.