Phase II Sorafenib With Radiation and Temozolomide in Newly Diagnosed Glioblastoma or Gliosarcoma

Inclusion Criteria:

1. Histopathologically proven diagnosis of glioblastoma. Since gliosarcoma is a variantof glioblastoma, gliosarcoma is also an eligible diagnosis.

2. Patients must have at least 1 block of tumor tissue available for submission to thecentral pathologist for analysis of gene expression status by QRT-PCR; there must beat least 1 cm^2 of tumor from the block when cut on a slide: fresh frozen tumor tissueacquisition is also encouraged, but not required. Unstained slide submission without ablock submission is not acceptable for study entry.

3. Diagnosis must be established by open biopsy or tumor resection. Patients who haveonly 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, andother complications before study registration.

6. All patients must sign an informed consent indicating that they are aware of theinvestigational nature of this study.

7. A diagnostic contrast-enhanced MRI or CT scan (if MRI is contraindicated) of the brainmust be performed postoperatively in the period between surgery and initiation ofradiation 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 stableor 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 studyregistration, with adequate bone marrow function as defined below: Absolute neutrophilcount (ANC) >/= 1500 cells/mm^3; Platelets >/= 100,000 cells/mm^3;Hemoglobin >/= 10g/dl.

16. Adequate renal function, as defined below: Serum creatinine </= 1.7 mg/dl within 14days prior to study registration

17. Adequate hepatic function, as defined below: Bilirubin </= 2.0 mg/dl within 14 daysprior to study registration; ALT </= 2 x upper limit of normal range (ULN) within 14days prior to study registration; AST </= 2 x ULN range within 14 days prior to studyregistration

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 forpatients not on anti-coagulation treatment

20. Patients receiving anti-coagulation treatment with an agent such as warfarin or lowmolecular 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 areeligible provided that the patient has no active bleeding or pathological conditionthat carries a high risk of bleeding;

21. (20. continued) Patients on full-dose anticoagulants (e.g., warfarin) are eligibleprovided 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 oflow molecular weight heparin. (b) Patient has no active bleeding or pathologicalcondition that carries a high risk of bleeding.

22. If the patient's mental status precludes his/her giving informed consent, writteninformed consent may be given by the responsible family member.

23. For females of child-bearing potential, negative serum pregnancy test within 72 hoursprior 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 studyparticipation. Men should use adequate birth control for at least six months after thelast administration of sorafenib or temozolomide.

Exclusion Criteria:

1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless diseasefree 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; notethat prior chemotherapy for a different cancer is allowable.

5. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment arenot permitted.

6. Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting inoverlap of radiation fields.

7. Severe, active co-morbidity, defined as follows: Cardiac disease - Congestive heartfailure > class II New York Heart Association (NYHA). Patients must not have unstableangina (anginal symptoms at rest) or new onset angina (began within the last 3 months)or myocardial infarction within the past 6 months; Cardiac ventricular arrhythmiasrequiring anti-arrhythmic therapy; Acute bacterial or fungal infection requiringintravenous antibiotics at the time of registration; Chronic Hepatitis B or Cinfection;

8. (7. continued) Chronic Obstructive Pulmonary Disease exacerbation or other respiratoryillness requiring hospitalization or precluding study therapy at the time ofregistration; Hepatic insufficiency resulting in clinical jaundice and/or coagulationdefects;

9. (7. continued) Known history or symptoms and laboratory results consistent withAcquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition (note,however, that HIV testing is not required for entry into this protocol. The need toexclude patients with AIDS from this protocol is necessary because the treatmentsinvolved in this protocol may be significantly immunosuppressive); Major medicalillnesses or psychiatric impairments that in the investigator's opinion will preventadministration or completion of protocol therapy;

10. (7. continued) Active connective tissue disorders, such as lupus or scleroderma, thatin the opinion of the treating physician may put the patient at high risk forradiation toxicity; Arterial thrombotic or embolic events such as a cerebrovascularaccident including transient ischemic attacks within the past 6 months; Pulmonaryhemorrhage/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 offirst dose of study drug; Serious non-healing wound, ulcer, or bone fracture; Evidenceor history of bleeding diathesis or coagulopathy

12. Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolicpressure > 90 mmHg, despite optimal medical management.

13. Major surgery, open biopsy or significant traumatic injury within 4 weeks of firststudy 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 notwilling/able to use medically acceptable forms of contraception; this exclusion isnecessary because the treatment involved in this study may be significantlyteratogenic.

16. No tissue provided for histopathologic review and QRT-PCR analysis.