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

Conditions

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

Age:
18 Years and older
Gender:
Both

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 6.1.1.1.) 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.
Sponsor:
Sarah Cannon Research Institute Oncology Research Consortium
Dates:
12/13/2012
Last Updated:
Study HIC#:
1203009888