The patients eligible for this study are those diagnosed with glioblastoma or gliosarcoma who have recently undergone surgery and who have not been treated with radiation therapy or chemotherapy. This is called a phase II study. The purpose of the phase II study is to determine how effective Tarceva plus Temodar plus radiation is in controlling the growth of glioblastoma and gliosarcoma. All patients will receive radiation and Temodar plus Tarceva. There is no "placebo" drug.

This is a Phase II Study of Tarceva plus Temodar during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma. The efficacy and safety profile of Tarceva in combination with radiation therapy plus Temodar will be studied. In addition, correlations between response to treatment and epidermal growth factor receptor (EGFR) status as well as other molecular markers of tumor prior to treatment will be explored. Patients will be stratified according to enzyme inducing anti epileptic drug (EIAED) use. Group A (not on EIAEDs) will take 100 milligrams (mg) Tarceva/day during radiotherapy and start with a dose of 150 mg Tarceva/day two weeks after radiotherapy. Group B (on EIAEDs) will take 200mg Tarceva/day during radiotherapy and start with a dose of 300 mg Tarceva/day two weeks after radiotherapy. Both groups will take 75 mg/m^2 Temodar/day during radiotherapy and 200 mg/m^2 Temodar/day x 5 two weeks after radiotherapy. Intrapatient Tarceva dose escalation may occur every two weeks after radiotherapy until the appearance of a particular rash severity. The maximum dose allowed is 200 mg for group A and 500 mg for group B.

Inclusion Criteria:

• Patients with histologically proven intracranial glioblastoma multiforme (GBM) and gliosarcoma (GS) will be eligible for this protocol.
• Diagnosis will have been established by biopsy or resection no more than 5 weeks prior to treatment.
• An magnetic resonance imaging (MRI) or computer tomography (CT) must be obtained within 14 days of treatment. The use of MRI rather than CT is preferred. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for assessment of tumor status.
• Patients without measurable or assessable disease are eligible.
• Patient must not have had prior cranial radiation therapy.
• Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
• Patients who received Gliadel wafers at the time of original resection will be excluded.
• Patients must have a plan to begin partial brain radiotherapy the same day as Tarceva and temozolomide.
• Radiotherapy must be a) at the Radiation Oncology Department of the University of California San Francisco or b) at an affiliated site such that a radiation oncologist at UCSF can provide assurance that radiation can be performed as specified.
• Radiotherapy must be given by external beam to a partial brain field in daily fractions of 1.8 to 2.0 Gy, to a planned total dose to the tumor of 5940-6100 cGy.
• Stereotactic radiosurgery and brachytherapy will not be allowed.
• Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with Tarceva and temozolomide.
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
• Patients must be registered in the UCSF Neuro-Oncology database prior to treatment with study drug.
• Patients must sign an authorization for the release of their protected health information.
• Patients must be 18 years or older, and with a life expectancy > 12 weeks.
• Patients must have a Karnofsky performance status of > 60.
• Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm^3, platelet count of > 100,000/mm^3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT, and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL or calculated creatinine clearance > 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
• 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. No exclusion to this study will be based on race.
• Patients must not have active infection.
• Patients must not be pregnant/breast feeding and must agree to practice adequate contraception.
• Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration.
• Patients must not be pregnant because of the uncertainty that study drug may be potentially embryotoxic. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation, and continue approximately 12 weeks after the study is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
• Patients must not have serious inter-current medical illness.
• Patient with recent thromboembolic disease (deep vein thrombosis and pulmonary embolism) are eligible if they are clinically stable and the thromboembolic event occurred more than 3 weeks prior to enrollment into this protocol.

Exclusion Criteria:

• Patients who do not meet one or more of the inclusion criteria above.