RO4929097and Bevacizumab in Treating Patients With Progressive or Recurrent Malignant Glioma

Inclusion Criteria: * Histologically confirmed malignant glioma (phase I) * Glioblastoma * Anaplastic astrocytoma * Anaplastic oligodendroglioma * Mixed anaplastic oligoastrocytoma * Histologically confirmed glioblastoma following radiotherapy and temozolomide (phase II) * Progressive or recurrent disease after conformal external-beam radiation therapy and concurrent temozolomide, followed by ≥ 1 adjuvant course of temozolomide * Measurable disease by MRI within the past 2 weeks * Tumor tissue form indicating availability of archived tissue from initial resection at diagnosis of malignant glioma completed and signed by a pathologist * Karnofsky performance status 60-100% * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9 g/dL * Total bilirubin normal * AST and ALT ≤ 2.5 times upper limit of normal * Creatinine normal OR creatinine clearance ≥ 60 mL/min * Urine protein: If proteinuria ≥ +2 protein, a protein level should be \< 1,000 mg by a 24-hour urine collection * Electrolytes (calcium, chloride, magnesium, potassium, phosphorus, sodium) within institutional normal limits * Fertile patients must use 2 forms of effective contraception before, during, and for ≥ 12 months (6 months phase II, bevacizumab arm only) after treatment * Negative pregnancy test * Not pregnant or nursing * At least 5 years since prior malignancy except nonmelanoma skin cancer, or carcinoma in situ of the cervix, breast, or bladder * Mini Mental State Exam score of ≥ 15 * Must be able to tolerate MRI Exclusion Criteria: * No serious concurrent infection or medical illness that would jeopardize the ability of the patient to receive the treatment outline in this protocol with reasonable safety * No history of allergic reactions attributed to compounds of similar chemical or biological composition to gamma-secretase inhibitor RO4929097 or bevacizumab * Must be able to swallow capsules * No malabsorption syndrome or other condition that would interfere with intestinal absorption * No baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female) * Not history of being serologically positive for hepatitis A, B, or C * No history of cirrhosis * No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, or hypokalemia despite adequate electrolyte supplementation * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * A history of torsades de pointes or other significant cardiac arrhythmias other than chronic, stable atrial fibrillation * Psychiatric illness and/or social situations that would limit compliance with study requirements * No serious or non-healing wound, ulcer, or bone fracture * No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months * No clinically significant cardiovascular disease, including any of the following: * Inadequately controlled hypertension (systolic BP \> 160 mm Hg and/or diastolic BP \> 90 mm Hg) despite antihypertensive medication * History of cerebrovascular accident or transient ischemic attack at any time * Myocardial infarction or unstable angina within the past 12 months * NYHA grade II-IV congestive heart failure * Serious and inadequately controlled cardiac arrhythmia * Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection) * Clinically significant peripheral vascular disease * No evidence of bleeding diathesis or coagulopathy * No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies * No requirement for antiarrhythmics or other medications known to prolong QTc * One or 2 prior treatment regimens allowed * Recovered from severe toxicity of prior therapy * At least 3 months since prior radiotherapy * At least 6 weeks since prior nitrosourea * At least 3 weeks since prior chemotherapy * At least 4 weeks since prior and no other concurrent investigational agents * At least 2 weeks since prior non-cytotoxic, FDA-approved agent (e.g., Tarceva \[erlotinib hydrochloride\], hydroxychloroquine, bevacizumab, etc.) * At least 28 days since any prior surgery * No prior γ-secretase inhibitors and/or bevacizumab * At least 10 days since prior and no concurrent enzyme-inducing anti-epileptic drug * No concurrent combination antiretroviral therapy for HIV-positive patients