Dasatinib or Placebo, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

1. Pregnancy, Nursing and Required Contraception - Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

* Pregnant women

* Nursing women

* Men or women of childbearing potential who are unwilling to employ adequate contraception throughout study treatment and for at least 12 weeks after study drug is stopped.

2. Prior Radiotherapy or Chemotherapy for Any CNS Neoplasm - Received any prior radiotherapy or chemotherapy for any CNS neoplasm (hormones, vitamins and growth factors are not considered chemotherapy for the purposes of this study.

3. Prior Surgery for Any CNS Neoplasm - Prior surgeries for any CNS neoplasms, other than surgery related to the current GBM diagnosis. Note: If Gliadel wafers are placed at time of primary resection, this would be considered prior therapy and patient would be ineligible.

4. Concurrent Illness or Disease - Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. Including but not limited to:

* History of bleeding diathesis

* Current use of chronic systemic anticoagulation therapy that cannot be discontinued (antiplatelet agents, Aspirin)

* Current chronic use of NSAIDs which cannot be discontinued

5. Pleural or Pericardial Effusions - Pleural or pericardial effusion of any grade.

6. Immunocompromised Status - Immunocompromised patients (other than that related to the use of corticosteroids) and patients known to be HIV positive and currently receiving antiretroviral therapy. Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.

7. Uncontrolled Intercurrent Illness - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

8. Other Investigational Agents - Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.

9. Other Active Malignancies - Other active malignancy ≤ 5 years prior to registration.

Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. Note: If there is a history of prior malignancy, they must not be receiving other specific treatment other than hormonal therapy for their cancer.

10. History of Cardiac or Metabolic Conditions:

* Myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

* Diagnosed congenital long QT syndrome

* Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)

* Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)

* Patients with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration.

11. Clinically Significant Cardiovascular Disease - Patients may not have any clinically significant cardiovascular disease including the following:

* Myocardial infarction or ventricular tachyarrhythmia within 6 months.

* Ejection fraction less than institutional normal

* Major conduction abnormality (unless a cardiac pacemaker is present)

Note: Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to ECG to rule out QTc prolongation. The patient may be referred to a cardiologist at the discretion of the principal investigator.

Patients with underlying cardiopulmonary dysfunction should be excluded from the study.

12. Congestive Heart Failure - New York Heart Association classification ≥ Class II Congestive Heart Failure.

13. Prohibited or Restricted Concomitant Treatments - Currently taking one of the following medications:

* Enzyme inducing anti-convulsants (EIACs) Note: To be eligible, patient must be switched to non-EIAC medications ≥7 days prior to registration. See protocol for a list of EIAC and non-EIAC medications.

* Potent inhibitors of CYP3A4 which cannot be discontinued. See protocol for a list of medications known to inhibit CYP3A4.

* Medications known to prolong QT interval which cannot be discontinued or switched. See Appendix II for a list of medications which are known to prolong the QT interval.

* Medications that may possibly prolong QT interval and produce a QTc that is ≥ 60 msec or a QTcF that is ≥ 450 msec. See Appendix II for a list of medications that may possibly prolong QTc.

* St. John's Wort

* H2 blockers or proton pump inhibitors (PPIs), such as famotidine (Pepcid) and omeprazole (Prilosec) respectively, which cannot be discontinued or switched to locally acting agents, such as Maalox, Mylanta and TUMS.

14. Allergy to Antibiotic Prophylaxis Medications - Severe allergy to sulfa medications and dapsone and pentamidine.

What this study is about