Phase I Portion of Phase I/II Sorafenib With Radiation and Temozolomide in Newly Diagnosed Glioblastoma or Gliosarcoma

Inclusion Criteria:

1. Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variant of glioblastoma, gliosarcoma is also an eligible diagnosis.
2. Patients must have at least 1 block of tumor tissue available for submission to the central pathologist for analysis of gene expression status by QRT-PCR; there must be at least 1 cm\^2 of tumor from the block when cut on a slide: fresh frozen tumor tissue acquisition is also encouraged, but not required. Unstained slide submission without a block submission is not acceptable for study entry.
3. Diagnosis must be established by open biopsy or tumor resection. Patients who have only had a stereotactic biopsy are not eligible..
4. The tumor must have a supratentorial component.
5. Patients must have recovered from the effects of surgery, postoperative infection, and other complications before study registration.
6. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
7. A diagnostic contrast-enhanced MRI or CT scan (if MRI is contraindicated) of the brain must be performed postoperatively in the period between surgery and initiation of radiation therapy.
8. Therapy must begin \</=5 weeks after the most recent brain tumor surgery.
9. History/physical examination within 14 days prior to study registration.
10. Neurologic examination within 14 days prior to study registration.
11. Documentation of steroid doses within 14 days prior to study registration and stable or decreasing steroid dose within 5 days prior to registration.
12. Karnofsky performance status of \>/= 60.
13. Age \>/= 18 years.
14. Patients with well-controlled hypertension are eligible (systolic blood pressure of \</= 140 mgHg or diastolic pressure \</= 90 mgHg).
15. Complete blood count (CBC)/differential obtained within 14 days prior to study registration, with adequate bone marrow function as defined below: Absolute neutrophil count (ANC) \>/= 1500 cells/mm\^3; Platelets \>/= 100,000 cells/mm\^3;Hemoglobin \>/= 10 g/dl.
16. Adequate renal function, as defined below: Serum creatinine \</= 1.7 mg/dl within 14 days prior to study registration
17. Adequate hepatic function, as defined below: Bilirubin \</= 2.0 mg/dl within 14 days prior to study registration; ALT \</= 2 x upper limit of normal range (ULN) within 14 days prior to study registration; AST \</= 2 x ULN range within 14 days prior to study registration
18. Fasting cholesterol \< 300 mg/dL (9.0 mmol/L) and fasting triglycerides \< 2.5 times ULN
19. International normalized ratio (INR) \< 1.5 or a PT/PTT within normal limits for patients not on anti-coagulation treatment
20. Patients receiving anti-coagulation treatment with an agent such as warfarin or low molecular weight heparin may be allowed to participate with the following criteria: For patients on prophylactic anticoagulation therapy (low-dose warfarin): INR level \< 1.5; Patients on prophylactic dose or full dose low molecular weight heparins are eligible provided that the patient has no active bleeding or pathological condition that carries a high risk of bleeding;
21. (20. continued) Patients on full-dose anticoagulants (e.g., warfarin) are eligible provided that both of the following criteria are met: (a) Patient has an in-range INR (usually between 2-3) on a stable dose or oral anticoagulant or on a stable dose of low molecular weight heparin. (b) Patient has no active bleeding or pathological condition that carries a high risk of bleeding.
22. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member.
23. For females of child-bearing potential, negative serum pregnancy test within 72 hours prior to starting temozolomide
24. Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least six months after the last administration of sorafenib or temozolomide.

Exclusion Criteria:

1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for \>/= 3 years.
2. Recurrent or multifocal malignant gliomas
3. Metastases detected below the tentorium or beyond the cranial vault.
4. Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable.
5. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted.
6. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields.
7. Severe, active co-morbidity, defined as follows: Cardiac disease - Congestive heart failure \> class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Hepatitis B or C infection;
8. (7. continued) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
9. (7. continued) Known history or symptoms and laboratory results consistent with Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition (note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive); Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy;
10. (7. continued) Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity; Arterial thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months; Pulmonary hemorrhage/bleeding event \> Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 within 4 weeks of first dose of study drug;
11. (7. continued) Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of first dose of study drug; Serious non-healing wound, ulcer, or bone fracture; Evidence or history of bleeding diathesis or coagulopathy
12. Uncontrolled hypertension defined as systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management.
13. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
14. Use of St. John's Wort or rifampin (rifampicin).
15. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
16. No tissue provided for histopathologic review and QRT-PCR analysis.