Phase I-II Everolimus and Sorafenib in Recurrent High-Grade Gliomas

• INCLUSION CRITERIA:

General Inclusion Criteria

• Patients with histologically proven recurrent intracranial malignant glioma will be eligible for the phase I/II component of this protocol. Malignant glioma includes glioblastoma (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified (NOS) (not otherwise specified). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made.
• 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 at all sites except the National Institutes of Health (NIH).
• Patients must be greater than or equal to 18 years old.
• Patients must have a Karnofsky performance status of greater than or equal to 60.
• No more than 2 prior chemotherapies and 1 relapse. Prior bevacizumab therapy is allowed.

-Patients must have recovered from the toxic effects of prior therapy: >3 weeks for biologic therapies or non-cytotoxic therapies, >4 weeks for cytotoxic therapies, and >6 weeks for nitrosoureas. Any questions related to the definition of non- cytotoxic agents should be directed to the Study Chair.

NOTE: 13 cis-retinoic acid (Accutane) as biologic therapy has a washout period of 14 days.

• Patients must have adequate bone marrow function (white blood cell (WBC) >= 3.0 x 10^9/L, absolute neutrophil count (ANC) >= 1.5 X 10^9/L, platelet count of >=100 x 10^9/L, and hemoglobin >= 10 gm/dL), adequate liver function (Serum glutamic oxaloacetic transaminase (SGOT) and bilirubin 3 weeks from surgery.
• Residual disease following resection of recurrent malignant glioma is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/ MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively, within 14 days prior to registration. If the 96-hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
• Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 12 weeks from the completion of radiation therapy to registration; except if patients underwent surgery within 12 weeks and pathology is consistent with recurrent tumor.
• Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon either positron emission tomography (PET) or Thallium scanning, magnetic resonance (MR) spectroscopy or surgical/pathological documentation of disease.
• Women of childbearing potential must have a negative beta human chorionic gonadotropin (B-HCG) pregnancy test documented within 7 days prior to taking the first dose of study medications.
• Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the international normalized ratio (INR) should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

Phase I Inclusion Criteria:

The following modifications to the general eligibility criteria apply to Phase I patients only.

-Patients may have had treatment for any number of prior relapses. Relapse is defined as progression following initial therapy (i.e., surgery and radiation+/- chemo if that was used as initial therapy).

Phase II Inclusion Criteria:

Phase II patients must meet the following Eligibility Criteria in addition