Status:
TERMINATED
Safety and Efficacy of INC280 and Buparlisib (BKM120) in Patients With Recurrent Glioblastoma
Lead Sponsor:
Novartis Pharmaceuticals
Conditions:
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
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
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 PTE...
Detailed Description
This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD and/or to identify the recommended phase II dose (RP2D) for the combination of INC280 and b...
Eligibility Criteria
Inclusion
- ≥ 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
- 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%.
Key Trial Info
Start Date :
January 9 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 23 2016
Estimated Enrollment :
43 Patients enrolled
Trial Details
Trial ID
NCT01870726
Start Date
January 9 2014
End Date
December 23 2016
Last Update
May 30 2018
Active Locations (13)
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1
Dana Farber Cancer Institute SC
Boston, Massachusetts, United States, 02215
2
Columbia University Medical Center- New York Presbyterian Dept of Oncology
New York, New York, United States, 10032
3
Memorial Sloan Kettering Cancer Center Neurology
New York, New York, United States, 90033
4
Duke University Medical Center Duke - Baker
Durham, North Carolina, United States, 27710