Inclusion Criteria

Criteria:

- Creatinine < = 1.5 mg/dL or creatinine clearance = > 60 mL/min

- At least 28 days since prior major surgery or open biopsy

- INR < = 1.5

- Not pregnant or nursing

- Negative pregnancy test

- Karnofsky performance status 60-100%

- SGOT and SGPT < 2 times upper limit of normal (ULN)

- Bilirubin < 2 times ULN

- Life expectancy = > 12 weeks

- WBC = > 3,000/μL

- ANC= > 1,500/mm³

- Platelet count = > 100,000/mm³

- Hemoglobin = > 10 g/dL (transfusion allowed)

- At least 21 days since prior radiotherapy (groups 2 and 3)

- No prior Gliadel® wafers

- No concurrent major surgery

- Fertile patients must use effective contraception prior to, during, and for at least
6 months after completion of study treatment

- At least 28 days since prior significant traumatic injury No evidence of bleeding
diathesis or coagulopathy

- No serious or nonhealing wound, ulcer, or bone fracture

- No history of other cancer (except nonmelanoma skin cancer or carcinoma in situ of
the cervix), unless in complete remission and off of all therapy for that disease for
a minimum of 3 years

- No history of abdominal fistula, gastrointestinal perforation, intra-abdominal
abscess gastrointestinal bleeding or diverticulitis within the past 6 months

- No prior cranial radiotherapy (group 1 only)

- No prior aflibercept

- No prior treatment for brain tumors, except concurrent radiotherapy and temozolomide
or 2 or fewer 28-day courses of adjuvant temozolomide (groups 2 and 3)

- No prior or concurrent cytotoxic drug therapy, non-cytotoxic drug therapy, or
experimental drug therapy for brain tumors (group 1 only)

- No concurrent major surgery

- No known hypersensitivity to CHO cell products or other recombinant human antibodies

- No history of hypersensitivity to a recombinant protein whereby reaction occurs
during or immediately after infusion

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to other study agents

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness or social situation that would limit compliance with
study requirements

- No clinically significant cardiovascular disease within the past 6 months, including
any of the following:

History of ischemic or hemorrhagic stroke

- Myocardial infarction, coronary artery bypass graft, or unstable angina

- New York Heart Association class III-IV congestive heart failure, serious cardiac
arrhythmia requiring medication, or unstable angina pectoris

- Clinically significant peripheral vascular disease

- Pulmonary embolism, deep vein thrombosis, or other thromboembolic event

- No disease that will obscure toxicity or dangerously alter drug metabolism

- Recovered from all prior therapy

- More than 28 days since prior and no concurrent investigational agents

- More than 7 days since prior core biopsy

- At least 23 days since prior temozolomide (groups 2 and 3)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent full-dose anticoagulants (e.g., warfarin or low molecular-weight
heparin)

- Prophylactic doses allowed

- No concurrent routine prophylactic use of filgrastim (G-CSF)

- No other concurrent anticancer therapy (including chemotherapy, radiotherapy,
hormonal treatment, or immunotherapy)

- Concurrent enzyme-inducing antiepileptic drugs (EIAED) or non-EIAED allowed

- Urine protein:creatinine ratio < = 1 or 24-hour urine protein < = 500 mg

- No 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 therapy