Hypofractionated Stereotactic Radiotherapy With Bevacizumab in the Treatment of Recurrent Malignant Glioma

Inclusion Criteria:

* Patients must have EITHER
* Histologically confirmed intracranial malignant glioma of the following types: Glioblastoma, Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), Anaplastic oligo-astrocytoma (AOA) also called anaplastic mixed gliomas, Malignant glioma NOS (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade (malignant) glioma is made.

OR

* Histologically confirmed low grade (WHO grade II) gliomas (such as low grade astrocytoma, low grade oligodendroglioma, low grade oligo-astrocytoma (mixed gliomas), or low grade glioma NOS) IF there is radiographic evidence by MRI of malignant transformation but histologic confirmation of high grade (malignant) transformation would not be otherwise undertaken for routine clinical care. Inclusion of patients in this group will allow increased accrual rapidity by enrolling patients who are otherwise ineligible for almost all malignant glioma trials yet whom are treated presumptively for malignant glioma. The primary aim of the phase I study is not determination of efficacy. Therefore, inclusion of such patients will not affect efficacy analyses.

Participating site confirmation is adequate.

* Able to undergo brain MRI scans.
* MRI scan with gadolinium contrast showing geographically-circumscribed tumor ≤40 cc incorporating both enhancing and non-enhancing volume. This is calculated by the product of maximum measurements in 3 dimensions divided by 2. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI. (The MRI must be performed on a steroid dosage that has been stable or decreasing for at least 5 days. Patients on no steroids are eligible. If the steroid dose is increased between date of imaging and registration, a new baseline MRI is required).
* Prior treatment with approximately 60 Gy of radiotherapy.
* Patients must have recovered from the toxic effects of prior therapy including but not limited to:
* An interval of ≥ 4 weeks (28 days) from prior cytotoxic therapy except 6 weeks from nitrosoureas
* An interval of ≥ 1 week (7 days) from any non-cytotoxic agents
* An interval of ≥ 3 months from the completion of radiation therapy
* Absolute neutrophil count ≥ 1,500/mm3.
* Platelet count ≥ 100,000/mm3.
* Hemoglobin ≥ 10 g/dl.
* Serum creatinine ≤ 2 times upper limit of normal.
* Total bilirubin ≤ 2 times upper limit of normal.
* SGOT and SGPT both ≤ 3 times upper limit of normal.
* ≥18 years of age.
* Karnofsky Performance Score ≥ 60
* Life expectancy ≥ 12 weeks
* Men and women with reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
* Written informed consent prior to registration on study.

Exclusion Criteria:

* Prior treatment with radiosurgery
* Prior disease progression/recurrence during or immediately following treatment with bevacizumab. Any question should be directed to the PI.
* Multicentric glioma
* Other malignancy (with the exception of cervical carcinoma in situ or basal cell carcinoma of the skin) for which there has been treatment within the last 3 years
* Serious medical or psychiatric illness that would in the opinion of the investigator interferes with the prescribed treatment.
* Pregnant or breast feeding women
* Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg)
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* Grade 2 or greater congestive heart failure
* History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 months prior to Day 1
* Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
* History of hemoptysis ≥1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
* Serious, non-healing wound, active ulcer, or untreated bone fracture
* Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening
* Known hypersensitivity to any component of bevacizumab
* History of peptic ulcer within the last 6 months
* Clinically significant peripheral vascular disease
* Craniotomy wound that has not sufficiently healed
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
* Glioma showing prior spontaneous hemorrhage as determined from the clinical history or from any preoperative CT or MRI scan (excluding grade 1 punctate, incidentally found).
* Longest uni-dimensional measurement of contrast enhancing tumor ≥ 4cm. Tumors exceeding this limit may be eligible and any question should be directed to a Radiation Oncology Investigator and the MSK PI.
* Tumor must not invade the corpus callosum
* Tumor must not invade the brainstem
* Suspected or documented radionecrosis