DISEASE CHARACTERISTICS:

• Histologically confirmed intracranial malignant glioma, including any of the following:

  • Glioblastoma multiforme
  • Gliosarcoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
  • Malignant astrocytoma not otherwise specified
• Must have evidence for tumor progression by MRI or CT scan
• Prior recent resection of recurrent or progressive tumor allowed
• Must have disease progression after prior radiotherapy

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%
• Life expectancy > 8 weeks
• WBC ≥ 3,000/μL
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 g/dL (transfusion allowed)
• SGOT < 2 times upper limit of normal (ULN)
• Bilirubin < 2 times ULN
• Creatinine < 1.5 mg/dL OR creatinine clearance > 60 cc/min
• Serum sodium, calcium, potassium, chloride, and magnesium within normal limits
• Proteinuria ≤ 1+ and urine protein:creatinine ratio ≤ 1.0 OR 24-hour urine protein < 1,000 mg
• QTc < 460 msec by ECG
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
• PT/PTT ≤ 1.5 time the upper limit of normal

Exclusion criteria:

• Any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
• Significant active cardiac, hepatic, renal, or psychiatric diseases
• Known malignancy that has required treatment in the past 12 months and/or is expected to require treatment in the next 12 months (except nonmelanoma skin cancer or carcinoma in situ of the cervix)
• Active infection
• Any disease that will obscure toxicity (e.g., vasculitis, congenial hypercoagubility syndromes, uncontrolled primary hypertension, or idiopathic thrombocytopenia)

• Evidence of significant recent hemorrhage on mandatory CT scan (defined as 1 cm or more of acute blood) of the brain within 7 days of patient accrual with the following exceptions:

  • Resolving hemorrhagic changes related to surgery
  • Presence of punctate hemorrhages in the tumor
• Serious or non-healing wound, ulcer, or bone fracture
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• Significant traumatic injury within the past 28 days

• Clinically significant cardiovascular disease including:

  • History of cerebrovascular accident or transient ischemic attack within the past 6 months
  • Inadequately controlled hypertension (defined as systolic blood pressure [BP] >160 mm Hg and/or diastolic BP > 100 mm Hg on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • Myocardial infarction or unstable angina within the past 6 months
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Unstable angina pectoris
  • Symptomatic peripheral vascular disease
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Evidence of bleeding diathesis or coagulopathy
• Known gastrointestinal (GI) disease or history of GI surgery that could interfere with the absorption of orally administered medication
• Ongoing vomiting

• Active cardiac disease, as defined by the following:

  • Significant cardiac event (including symptomatic heart failure or evidence of cardiac ischemia within 3 months of first dose) or presence of any cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia
  • Clinically significant arrhythmia (multifocal premature ventricular contraction, bigeminy, trigeminy, ventricular tachycardia, bradycardia) that is symptomatic or requires treatment (i.e., CTCAE grade 3), or asymptomatic sustained ventricular tachycardia
  • Previous history of QTc prolongation with other medication
  • Congenital long QT syndrome
  • Previous history of LVEF < 45% by MUGA or ECHO in patients with previous anthracycline therapy (total dose > 450 mg/m²) or significant cardiovascular disease or chest irradiation, as determined by the investigator
  • Cardiac arrhythmia serious enough to require therapy (i.e. drugs, AID), angina, symptomatic congestive heart failure, and/or a cardiac ejection fraction < 45%
  • Prior serious cardiac disease, defined as prior myocardial infarction unless a recent cardiac evaluation (within the past 3 months) demonstrated no significant coronary artery disease (i.e., a negative stress test) and no myocardial wall dysfunction

• Known or suspected primary muscular or neuromuscular disease (e.g., muscular dystrophy or myasthenia gravis)

  • Steroid myopathy allowed

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics
• Recovered from all prior therapy
• At least 4 weeks since prior radiotherapy
• At least 2 weeks since prior investigational agent
• At least 4 weeks since prior cytotoxic therapy
• At least 2 weeks since prior vincristine
• At least 6 weeks since prior nitrosoureas
• At least 3 weeks since prior procarbazine
• At least 1 week since prior non-cytotoxic agents, including interferon, tamoxifen, thalidomide, or cis-retinoic acid (radiosensitizer does not count)

Exclusion criteria:

• Prior coronary bypass surgery
• Prior angioplasty
• Prior bevacizumab
• Major surgical procedure or open biopsy within the past 28 days
• Core biopsy within the past 7 days
• Concurrent major surgery
• Concurrent chemotherapy, radiotherapy, immunotherapy, or investigational agents
• Concurrent anti-coagulation or anti-platelet medication (including acetylsalicylic acid, non-steroidal anti-inflammatories, cyclooxygenase-2 inhibitors)
• Concurrent use of other standard chemotherapeutics or investigative agents or vasoconstrictors for the treatment of migraine (ergotamine, zolmitriptan, sumatriptan)
• Concurrent use of other drugs that have been shown to potentially prolong the QTc interval