Clinical Trial Finder

Inclusion Criteria:

Phase I ONLY:

• - Advanced, metastatic solid tumor 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:

• - Progressive GBM after treatment with surgical resection (if possible) and 1st line radiation/chemotherapy.

• - No previous treatment with a PI3K inhibitor.

Previous treatment with bevacizumab as a component of first-line therapy is allowed.

• - At least one measurable or evaluable lesion definable by MRI scan.

Disease must be measurable by RANO criteria.

• - Archival tumor tissue available for correlative testing.

ALL PATIENTS:

• - Patient must be ≥ 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 ≥ 4 weeks or ≥ 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.

• - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• - Life expectancy of ≥ 3 months.

• - Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

• - Patients with diarrhea ≥ grade 2.

• - Patients with uncontrolled type I or type II diabetes mellitus, defined as a fasting plasma glucose ≥120 mg/dL.

• - Patients who have received prior treatment with a P13K inhibitor.

• - 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.

• - Symptomatic pericarditis.

• - Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug.

• - Patients with clinical history of hemoptysis or hematemesis (defined as having bright red blood of ½ teaspoon or more per episode) ≤1 month prior to study enrollment.

• - Patients with any history of a bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation) - Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial.

• - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy.

• - Patients who have been treated with any hematopoietic colony-stimulating factors (e.g. G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug.

Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment may be continued.

• - Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury ≤ 28 days prior to entry.

This is an open-label, non-randomized Phase I study of patients with advanced refractory solid tumors followed by a Phase II study for the second-line treatment of patients with relapsed/refractory glioblastoma multiforme. In the phase I part of the study the optimal dose of BKM120 when combined with bevacizumab was determined. In the Phase II part of this study, patients with relapsed/refractory GBM following first line therapy are being treated with the BKM120/bevacizumab combination. Limited BKM120 pharmacokinetic evaluation will be performed on all patients treated during this part of the study. Patients will be reevaluated for response to treatment after 2 cycles (8 weeks). Patients with objective response or stable disease will continue treatment, with subsequent reevaluations every 8 weeks, until disease progression or unacceptable toxicity occurs. Two populations of patients with relapsed/refractory GBM will be treated in the Phase II trial: 1) patients with no previous exposure to bevacizumab (N= 55) and 2) patients who received bevacizumab as part of first-line combined modality treatment (N= 20).

Arms

Experimental: BKM120/Bevacizumab

Phase I: BKM 120 orally (PO) once daily (dose is 60mg or 80mg). Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks Phase II: BKM 120 orally (PO) once daily - dose is optimal dose determined in Phase I. Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks

Interventions

Drug: - Bevacizumab

Bevacizumab 10 mg/kg IV every 2 weeks

Drug: - BKM120

BKM120 orally (PO) once daily