A Phase I/II Study of the Combination of BKM120 and Bevacizumab, Glioblastoma Multiforme


Brain and Nervous System

Trial Phase

Phase I-II

Trial Purpose and Description

Trial Purpose

Primary Objective Phase I
To establish the optimal dose of BKM120 that can be administered in combination with a standard dose of bevacizumab.
Primary Objective Phase II
To evaluate the efficacy of the BKM120/bevacizumab combination in patients with relapsed/refractory GBM. For evaluation of efficacy, patients previously treated with bevacizumab will be considered separately from those with no previous bevacizumab treatment.

Participation Guidelines

18 Years and older

Eligibility Criteria

Phase I Only Inclusion Criteria:

  • Advanced, metastatic solid tumor (including patient with GBM) that has progressed after standard therapy, or is a tumor type resistant to therapy and for which bevacizumab is clinically appropriate.
  • Patient may have measurable disease or non-measureable disease as defined by RECIST v1.1 criteria.

Phase II Only Inclusion Criteria:

  • Progressive GBM after treatment with surgical resection (if possible) and 1st line radiation/chemotherapy.
  • At least one measurable or evaluable lesion definable by MRI scan. Disease must be measurable per adapted MacDonald criteria.
  • Archival tumor tissue available for correlative testing for identification of PI3K pathway activation.

Inclusion Criteria for All Patients:

  • Patient must be &ge 4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy, or chemotherapy). Patients who receive a small molecule targeted therapy as part of their first line treatment regimen must be &ge 4 weeks or &ge 5 half lives from administration of last dose, whichever is shorter. The patient must have recovered from or come to a new chronic or stable baseline from all treatment-related toxicities.
  • Previous treatment with bevacizumab as a component of first-line therapy is allowed.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Life expectancy of &ge 3 months.
  • Adequate hematologic function defined by: Absolute neutrophil count (ANC) &ge1500/&muL Hemoglobin (Hgb) &ge 9 g/dL Platelets &ge 100,000/L
  • Adequate liver function defined by: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) within normal limits (WNL) (or &le 3.0 x upper limit of normal (ULN) in patients with liver metastases Serum bilirubin WNL (or &le 1.5 x the institutional ULN in patients with liver metastases or total bilirubin &le 3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert Syndrome).
  • Adequate renal function, defined by: Serum creatinine &le 1.5 x ULN or calculated creatinine clearance 50 mL/min by the Cockcroft-Gault method:
  • GFR = (140-age) x (weight/kg) x (0.85 if female)
  • (72 x serum creatinine mg/dL)
  • Urine dipstick for proteinuria < 2+ at screening. Patients with dipstick urinalysis 2+ proteinuria at baseline should undergo a 24-hour urine collection, and must demonstrate 1 g of protein/24 hours to be eligible.
  • Must be 18 years of age.

Exclusion Criteria:

  • Patients with diarrhea &ge grade 2.
  • Patients who have received prior treatment with a P13K inhibitor.
  • Patients with the following mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of &ge 10 in the PHQ-9 or a cut-off score of &ge 15 in the GAD-7 mood scale, respectively, or selects a positive response of &bdquo1, 2, or 3? to question 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of total score or the PHQ-9) &ge grade 3 anxiety or depression (See Section 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.
  • Patients with uncontrolled type I or type II diabetes mellitus, defined as a fasting plasma glucose &ge120 mg/dL.
  • Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).
  • Patient has active cardiac disease including any of the following: Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO) QTc > 480 msec on screening ECG (using the QTcF formula) Angina pectoris that requires the use of anti-anginal medication Ventricular arrhythmias except for benign premature ventricular contractions Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication Conduction abnormality requiring a pacemaker Valvular disease with documented compromise in cardiac function.
Sarah Cannon Research Institute Oncology Research Consortium
Last Updated:
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