Dasatinib Plus Radiation Therapy/Temozolomide in Newly-Diagnosed Glioblastoma

Inclusion Criteria: 1. Patients with newly diagnosed histologically proven intracranial supratentorial GBM or gliosarcoma (GS) will be eligible for this protocol. Patients will not be eligible if the original histology was a grade II or III glioma and a subsequent histological diagnosis of a GBM is made. 2. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. 3. Diagnosis will have been established by biopsy or resection 14-28 days prior to registration. In order to permit healing, patients should not receive Day 1 of treatment until at least 14 days after surgery. 4. Patients must not have had prior cranial RT 5. Patients must have a plan to begin partial brain RT on the same day as the first dasatinib dose and the first dose of TMZ. Radiotherapy can be performed at either MD Anderson or outside facilities. Radiotherapy must be given by external beam to a partial brain field in daily fractions of 180 to 200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. Stereotactic radiosurgery and brachytherapy will not be allowed. 6. Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors. 7. Patients must be \>/= 18 years old. 8. A contrast enhanced brain scan should be performed within 14 days prior to registration and on a corticosteroid dose that has been stable or decreasing for at least 5 days. If the corticosteroid dose is increased between the date of imaging and registration, then a new baseline MRI/CT is required. The same type of scan, i.e., MRI or CT, must be used throughout the period of protocol treatment for tumor measurement. The use of MRI rather than CT is preferred. 9. Patients must have a Karnofsky performance status of \>/= 60. 10. 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, SPGT and bilirubin \</= 2 times ULN), serum Na, K+, Mg\^2+, phosphate and Ca\^2+ \>/= Lower Limit of Normal (LLN) and adequate renal function (creatinine \</= 1.5 mg/dL or creatinine clearance \>/= 60 cc/min/1.73 m\^2) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion. 11. Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while enrolled in the study. 12. Women of childbearing potential must have a negative beta-HCG pregnancy test documented within 14 days prior to registration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Exclusion Criteria: 1. Patients must not have received prior Gliadel wafers. 2. Patients must not have received any investigational agents within 30 days prior to commencing study treatment. 3. 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. 4. 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. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. 6. Patients with the following invasive procedures: a) Major surgical procedure, open biopsy or significant traumatic injury \< 14 days prior to Day 1 therapy b) Anticipation of need for major surgical procedures during the course of the study c) Core biopsy within 7 days prior to Day 1 therapy. 7. Patients must not be pregnant/breastfeeding and must agree to practice adequate contraception. Breastfeeding should be discontinued if the mother is treated with dasatinib. 8. Patients with clinically significant cardiovascular disease: a) History of ischemic or hemorrhagic stroke within past 6 months b) Uncontrolled hypertension, defined as blood pressure \>140/90 mm Hg or systolic BP \>180 mm Hg if diastolic blood pressure \<90 mm Hg, on at least 2 repeated determinations on separate days within past 3 months c) Myocardial infarction, CABG or unstable angina within past 6 months d) New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months 9. ( 8. continued) e) Clinically significant peripheral vascular disease within past 6 months f) Pulmonary embolism, DVT, or other thromboembolic event within past 6 months. g) Diagnosed congenital long QT syndrome h) Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) i) Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec) j) Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration 10. Evidence of bleeding diathesis or coagulopathy or INR \>1.5. History of significant bleeding disorder unrelated to cancer, including: a) Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) c) Ongoing or recent (\</= 3 months) significant gastrointestinal bleeding 11. Patients with known HIV are ineligible for this study. 12. Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism. 13. Patients must not have received prior therapy with dasatinib for any indication. 14. Inclusion of Women and Minorities: Both men and women and members of all races and ethnic groups are eligible for this trial. 15. Patients on the following medication will be excluded: a) Anticonvulsants: Patients on Enzyme Inducing Anticonvulsants (EIAED) will be excluded. If patients were previously on EIAEDs that have been discontinued, patients must have been off EIAEDs for \>/= 2 weeks prior to initiation of dasatinib. It should also be noted whether patients were or were not previously receiving EIAEDs and the last date of administration of EIAEDs. 16. ( 15. continued) b) Antacids: Use of H2 blockers and proton pump inhibitors is prohibited because systemic antacids (H2 inhibitors, proton pump inhibitors) decrease dasatinib absorption. Patients who require antacids should use short acting, locally active agents (e.g., Maalox, Mylanta etc.). However, these agents should not be taken within either 2 hours before or 2 hours after the dasatinib dose. This is particularly important in patients with glioblastoma who are frequently on dexamethasone and prophylactic H2 blockers or proton pump inhibitors. 17. (15. continued) c) Anticoagulants/Anti-platelets: Patients on therapeutic (treatment) dose of anticoagulants (e.g. warfarin, low molecular-weight heparin) are not eligible. Patients are not allowed to take aspirin, clopidogrel, ticlopidine, Aggrenox. Patients on prophylactic anticoagulation may be enrolled and treated on study as long as their platelet count is monitored closely and maintained at \>75,000 while they are receiving Dasatinib. 18. (15. continued) d) Ibuprofen and other NSAIDS: Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDS) can inhibit platelet function. Patients may not take ibuprofen or other NSAIDs at study entry and must have stopped these agents \>/=7 days prior to starting dasatinib to allow for an appropriate wash-out period. 19. (15. continued) e) Inducers and Inhibitors of CYP3A4: Patients required to be on any of those drugs will be excluded (with the exception of Dexamethasone, but all efforts should be made to reduce the dose of dexamethasone). Patients may discontinue drug at least 7 days prior to starting dasatinib. 20. (15. continued) f) Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug at least 7 days prior to starting dasatinib) (1). quinidine, procainamide, disopyramide (2). amiodarone, sotalol, ibutilide, dofetilide (3). erythromycin, clarithromycin (4). chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide (5). cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.