Inclusion Criteria:

- Histologically proven diagnosis of glioblastoma or variants (gliosarcoma,
glioblastoma with oligodendroglial features, giant cell glioblastoma); patients will
be eligible if the original histology was a lower-grade glioma and a subsequent
histological diagnosis of glioblastoma or variants is made

- Patients must have shown unequivocal evidence for tumor progression on the previous
treatment regimen (prior to enrollment on this study) by magnetic resonance imaging
(MRI) scan of the brain with and without contrast within 14 days prior to
registration; the dose of steroids must be stable or decreasing for at least 5 days
prior to the scan

- Patients unable to undergo MRI because of non-compatible devices can be
enrolled, provided computed tomography (CT) scans are obtained and are of
sufficient quality; patients without non-compatible devices may not have CT
scans performed to meet this requirement

- Patients who have received prior treatment with interstitial brachytherapy,
stereotactic radiosurgery, or implanted chemotherapy sources, such as wafers of
polifeprosan 20 with carmustine, must have confirmation of progressive disease within
14 days prior to registration based upon nuclear imaging, MR spectroscopy, perfusion
imaging, or histopathology

- No more than 2 relapses

- No intratumoral hemorrhage or peritumoral hemorrhage, demonstrated by MRI or CT scan,
Common Terminology Criteria for Adverse Events (CTCAE) v. 4 grade 2 or greater, or
evidence of significant hemorrhage (regardless of CTCAE, v. 4 grade) defined as > 1
cm diameter of blood (including postoperative hemorrhage)

- Karnofsky performance scale >= 70%

- Leukocytes > 3,000/mm^3

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Hemoglobin (Hgb) >= 10.0 g/dL (Note: The use of transfusion or other intervention to
achieve Hgb >= 10.0 g/dL is acceptable)

- Platelets >= 100,000/mm^3

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
< 2.5 times institutional upper limit of normal

- Bilirubin =< 2.0 mg/dL

- Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min
(per 24-hour urine collection or calculated according to the Cockcroft-Gault formula)

- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5

- Urinary protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick

- Generally well-controlled blood pressure with systolic blood pressure =< 140 mm Hg
AND diastolic blood pressure =< 90 mm Hg within 5 days prior to registration; the use
of anti-hypertensive medications to control hypertension is permitted

- Women of childbearing potential must have a negative serum beta (β)-human chorionic
gonadotropin (HCG) pregnancy test within 14 days prior to registration

- Women of childbearing potential and male patients who are sexually active must
practice adequate contraception during therapy and for 180 days (6 months) afterwards

- No prior invasive malignancy (except non-melanomatous skin cancer) unless
disease-free for a minimum of 1095 days (3 years); (for example, carcinoma in situ of
the breast, oral cavity, or cervix are all permissible)

- No gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE, v. 4 grade
3 or greater within 30 days prior to study entry

- No severe, active co-morbidity, defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
180 days (6 months) prior to registration

- Transmural myocardial infarction within 180 days (6 months) prior to
registration

- History of stroke, cerebral vascular accident (CVA), or transient ischemic
attack within 180 days (6 months) prior to registration

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

- Chronic obstructive pulmonary disease (COPD) exacerbation or other respiratory
illness requiring hospitalization or precluding study therapy at the time of
registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

- Known acquired immune-deficiency syndrome (AIDS) based upon current CDC
definition; note, however, that human immunodeficiency virus (HIV) testing is
not required for entry into this protocol

- Known coagulopathy that increases risk of bleeding or a history of clinically
significant hemorrhages in the past

- History of non-healing wounds or ulcers, or bone fractures within 90 days (3
months) prior to registration

- No prior allergic reaction to the study drugs involved in this study

- No prior systemic cytotoxic chemotherapy within 28 days (42 days for nitrosoureas or
mitomycin C) prior to registration, or patients who have not returned to baseline or
=< CTCAE v. 4 grade 2 from adverse events (excluding alopecia) due to agents
administered more than 28 days prior to registration

- Patients who received non-cytotoxic drug therapy must be off treatment for at least
14 days prior to registration

- Prior treatment with anti-vascular endothelial growth factor(VEGF)-targeted
agents, AMG 386 therapy, or other molecules that inhibit angiopoietins or Tie2
receptor including, but not limited to, XL-820, XL-184, and CVX-060/PF-4856884
is not allowed regardless of time frame

- No patients who have not yet completed at least 21 days (30 days for prior monoclonal
antibody therapy) since ending other investigational device or drug trials, or who
are currently receiving other investigational treatments

- No treatment within 30 days prior to enrollment with strong immune modulators
including, but not limited to, systemic cyclosporine, tacrolimus, sirolimus,
mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide,
lenalidomide, and targeted immune modulators such as abatacept (CTLA-4-Ig),
adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept,
infliximab, or rituximab

- No prior radiotherapy within 90 days (3 months) prior to registration unless there is
either: a) histopathologic confirmation of recurrent tumor; or b) new enhancement on
MRI outside of the radiation treatment field

- No major surgical procedure (including craniotomy) or significant traumatic injury
within 28 days prior to registration or those patients who receive a non-central
nervous system (CNS) minor surgical procedures (e.g., core biopsy or fine-needle
aspiration) within 3 days prior to registration; there is no waiting period for
central line placement

- Prior therapy with anti-VEGF targeted agents (e.g. bevacizumab, cediranib,
vandetanib, aflibercept, sunitinib, sorafenib, etc.); prior therapy with thalidomide
and lenalidomide is allowed as long as treatment has not occurred within 30 days
prior to enrollment

- Prior therapy with thalidomide and lenalidomide is allowed as long as treatment has
not occurred within 30 days prior to enrollment

- No therapeutic anticoagulation with warfarin < 7 days prior to registration

- Therapeutic or prophylactic therapy with aspirin, a low-molecular weight
heparin, or a Factor Xa inhibitor is acceptable

- No history of venous or arterial thromboembolism within 12 months prior to
registration