|Inclusion Criteria:||1) Patients with histologically proven newly diagnosed GBM or gliosarcoma will be eligible for consent but will require confirmation of an unmethylated MGMT promoter to be eligible for treatment post RT. If MGMT is indeterminate or methylated, the patient is not eligible. Consent must be obtained prior to starting RT. Determination of MGMT status is strongly recommended to have been determined prior to starting RT to ensure that all treatment options available would still be possible for the ineligible patient. A pathology report of most recent surgery or biopsy must be available at registration.|
2) Patients must have at least 1 block of tumor tissue of sufficient size (at least 1 cm3) for analysis of MGMT status; CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged for tumor banking at local institution.
3) Diagnosis must be made by surgical excision, either partial or complete. Stereotactic biopsy will not be allowed because this will not provide sufficient tissue for the MGMT analysis.
4) The tumor must have a supratentorial component.
5) Post tumor resection, all patients must have a post operative MRI done no more than 96 hours after surgery or a study > 4 weeks (+/- 7 days) after surgery, but before initiation of radiation treatment in order for an accurate assessment to be done post RT. Another contrast enhanced MRI or CT scan must be performed on no steroids or a stable dose of steroids for 5 days or more, within 14 days before starting treatment with Bevacizumab and Erlotinib.
6) (5. continued) MR perfusion is optional but recommended. The same type of enhanced scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. Patients who can only get a CT scan will not be able to undergo MR Perfusion: a) Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study. b) The tumor must have no MGMT promoter methylation to qualify for protocol treatment post RT.
7) No chemotherapy is allowed prior to starting RT + Temozolomide including Gliadel Wafers.
8) Patients who have started RT + Temozolomide will not be eligible for treatment after RT unless consent was signed before RT began.
9) (8. continued) Eligible patients will start Bevacizumab and Erlotinib 4 weeks (+/- 7 days) after the completion of RT + Temozolomide. a) RT plans will need to be verified prior to treatment to confirm that the treatment plan was conducted as the protocol outlined or similar based on the PI assessment, such as IMRT. b) The patient must have completed the full course of RT with standard dose temozolomide (75 mg/m2 x 42 days +/- 3 days) prior to initiating Bevacizumab and Erlotinib.
10) Patients must be > 18 years old.
11) Patients must have a Karnofsky performance status of >/= 70.
12) Patients must have adequate bone marrow function (WBC > 3,000/mcL, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function (SGOT/SGPT and bilirubin < 3 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) before starting therapy. These tests must be performed within 7 days prior to registration step 2.
13) This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate.No exclusion to this study will be based on race.
14) All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign informed consent prior to registration and before undergoing any study-related procedures. Patients must sign an authorization for the release of their protected health information.