Aflibercept, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed or Recurrent Glioblastoma Multiforme, Gliosarcoma, or Other Malignant Glioma

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