|Inclusion Criteria:||1) Patients with histologically proven intracranial GBM or gliosarcoma (GS) will be eligible for this protocol. For Arms 2 and 3, patients with anaplastic gliomas (AGs), including anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified (NOS) will also be eligible.|
2) All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information. Patients must be registered in the ABTC Central Operations Office (ABTC COO) database prior to treatment with study drug.
3) Patients must be >/= 18 years old. Because aflibercept (VEGF Trap) interferes with growth plate maturation in animals, this agent may be inappropriate for use in patients <18 years of age. For this reason and because no dosing or adverse event (AE) data are available on the use of aflibercept (VEGF Trap) in children, patients <18 years of age are excluded from this study but may be eligible for future pediatric single-agent trials, if applicable.
4) A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required. The same type of scan, i.e., MRI or CT, must be used throughout the period of protocol treatment for tumor measurement. The use of MRI rather than CT is preferred.
5) Patients must have a life expectancy of > 12 weeks.
6) Patients must have a Karnofsky performance status of >/= 60.
7) Patients must have adequate bone marrow function (WBC > 3,000/Ál, ANC > 1,500/mm^3, platelet count of > 100,000/mm^3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT, SPGT and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL or creatinine clearance > 60 cc/min/1.73 m^2) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
8) Urine protein:creatinine ratio (UPCR) must be </=1. Subjects with UPCR > 1 will still be eligible if 24-hour urine protein is < 500 mg.
9) Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while enrolled in the study.
10) Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months after completion of aflibercept (VEGF Trap) therapy.
11) Women of childbearing potential must have a negative beta-HCG pregnancy test documented within 14 days prior to registration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
12) Diagnosis will have been established by biopsy or resection 14-28 days prior to registration. In order to permit healing, patients should not receive Day 1 of treatment with VEGF-Trap until at least 28 days after surgery.(Arm 1 only)
13) Patients must not have had prior cranial RT. (Arm 1 only)
14) Patients must have a plan to begin partial brain RT on the same day as the first dose of TMZ. The first aflibercept (VEGF Trap) infusion will be scheduled for 2 weeks after the start of RT and TMZ. (Arm 1 only)
15) Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors. (Arm 1 only)
16) Patients with anaplastic glioma (AG), including AA, AO, AMO, or malignant astrocytoma NOS will be eligible for Arms 2 or 3 of this protocol, in addition to patients with GBM and GS. (Arm 2 & 3 only)
17) Patients may have stable or recurrent disease. (Arm 2 & 3 only)
18) Patients must have an interval of 21 days or more from the completion of RT to study entry. (Arm 2 & 3 only)
19) Patients must not have received prior treatment for brain tumors, with the following exceptions: Concurrent RT and TMZ; 2 or fewer 28-day cycles of adjuvant TMZ. (Arm 2 & 3 only)
20) Patients must have recovered from the toxic effects of prior therapy: at least 23 days from prior treatment with TMZ. ( Arm 2 & 3 only)
21) Only patients with GBM or GS will be eligible for Arm 1 of this protocol.