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

Pre-registration Inclusion Criteria:

• Central Pathology Review - Central pathology review submission. This review is mandatory prior to registration to confirm eligibility.

Registration Inclusion Criteria:

• Age ≥ 18 years
• Histological Confirmation of Glioblastoma - Histologically confirmed newly diagnosed glioblastoma (GBM) (grade 4 astrocytoma) as determined by pre-registration central pathology review. Note: GBM with oligodendroglial features are not permitted in this study if they are 1p19q codeleted. Sites submitting GBM with oligodendroglial features will be asked to provide results of 1p/19q codeletion status.
• Measurable or Evaluable Disease - Measurable or evaluable disease by gadolinium MRI or contrast CT scan. Note: Patients who have had a gross total resection are eligible on the basis of evaluable disease.
• ECOG Performance Status 0, 1 or 2.
• Required Laboratory Values:

The following laboratory values obtained ≤ 14 days prior to registration.

• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin > 9.0 g/dL
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• SGOT (AST) ≤ 2.5 x ULN
• Creatinine ≤ 1.5 x ULN
• Required INR Value: The following INR value obtained ≤ 28 days prior to registration
• INR ≤ 1.5
• Urine or Serum Pregnancy Test - Negative urine or serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
• Written Informed Consent - Patient must provide written informed consent.
• Return to Enrolling Institution - Patient must be willing to return to Alliance enrolling institution for follow-up.
• Tissue Samples - Patient must be willing to provide tissue samples for research purposes.
• Patient must be willing to provide tissue samples for research purposes.
• Required Antibiotic Prophylaxis - Patient must be willing to comply with antibiotic prophylaxis with trimethoprim/sulfamethoxazole, pentamidine or dapsone.
• Grapefruit and Grapefruit Juice - Patient must be willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study treatment.
• Ability to Swallow - Patient must have the ability to take oral medication (dasatinib must be swallowed whole).
• Quality of Life (QOL) Questionnaires - Phase II patients only: Patients must be willing and able to complete QOL questionnaires independently or with the help of a caregiver.
• Other Anti-Tumor Drug Therapies - Patient must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with dasatinib and temozolomide.

Registration Exclusion Criteria:

• 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.
• 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.
• 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.
• 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 o