Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme

Patient Eligibility:

I. Pre-registration:

• Central pathology review submission. This review is mandatory prior to registration to confirm eligibility.

II. Registration Inclusion Criteria:

• ≥18 years of age
• Study 1: Histologic confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review.
• Study 2: Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review. NOTE: Variant gliosarcomas are eligible
• Evidence of tumor progression by MRI or CT scan following RT or following the most recent anti-tumor therapy. Patients who had surgical treatment at recurrence are eligible if there is imaging evidence of disease progression as compared to the first postoperative scan.
• Bidimensionally measurable or evaluable disease by MRI or CT scan.
• ECOG Performance Status (PS) 0, 1, or 2.
• Patient willing to discontinue use of aspirin or medications that inhibit platelet function ≥ 1 week prior to registration.
• Previous RT and ≥12 weeks since the completion of RT prior to registration.
• The following laboratory values obtained ≤ 21 days prior to registration.
• ANC ≥1500
• PLT ≥100,000
• Hgb >9.0 g/dL
• T. bili ≤1.5 x ULN
• SGOT (AST) ≤ 3 x ULN
• Creatinine ≤ ULN
• UPC ratio 150 mmHg or diastolic pressure >100 mmHg on anti-hypertensive medications).

NOTE: Patients with well-controlled hypertension are eligible.

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients (other than that related to the use of corticosteroids). NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this study.
• Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or prior surgical procedures affecting absorption) that impairs ability to swallow pills.
• Receiving therapeutic anticoagulation with Warfarin. NOTE: Prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices is allowed, provided that INR 450 msec)
• Patients may not have any clinically significant cardiovascular disease including the following:
• Myocardial infarction or ventricular tachyarrhythmia within 6 months.
• Prolonged QTc ≥ 480 msec (Fridericia correction)
• Ejection fraction less than institutional normal
• Major conduction abnormality (unless a cardiac pacemaker is present)

Note: Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (ECG) to rule out QTc prolongation. The patient may be referred to a cardiologist at the discretion of the principal investigator. Patients with underlying cardiopulmonary dysfunction should be excluded from the study.

• Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
• Known pleural or pericardial effusion of any grade
• Concomitant use of H2 blockers or proton pump inhibitors that cannot be discontinued or switched to locally acting agents (i.e. famotidine or omeprazole.)
• Use of the following Enzyme Inducing Anti-Convulsive (EIAC) medications is prohibited ≤ 7 days prior to registration: carbamazepine (Tegretol®, Tegretol XR®, Carbatrol®), phenytoin (Dilantin®, Phenytek®), fosphenytoin (Cerebyx®), phenobarbital, pentobarbital and primidone (Mysoline®). Note: Many antiepileptic drugs induce hepatic enzymes. Because dasatinib is metabolized by hepatic enzymes, patients taking antiepileptic medications th