Temozolomide and Radiation Therapy With or Without Bevacizumab in Treating Patients With Newly Diagnosed Glioblastoma

Inclusion Criteria:

• Histologically confirmed glioblastoma (gliosarcoma closed to accrual as of 07-13-10)

  • WHO grade IV disease
  • Tumor must have a supratentorial component

• Has undergone partial or complete surgical resection of tumor within the past 3-5 weeks

  • Diagnosis must be made by surgical excision (not by stereotactic biopsy)
  • No significant postoperative hemorrhage, defined as > 1 cm diameter of blood in the tumor cavity by MRI or CT scan

• Has ≥ 1 block of tumor tissue of sufficient size available for analysis of MGMT status and determination of molecular profile

  • At least 1 cm³ of tissue composed primarily of tumor must be present
  • No CUSA (Cavitron ultrasonic aspirator)-derived material
• No recurrent or multifocal malignant glioma
• No metastases detected below the tentorium or beyond the cranial vault
• Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,800/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
• ALT and AST ≤ 3 times normal
• Bilirubin ≤ 2.0 mg/dL
• PT/INR < 1.4 (for patients not on warfarin)
• Creatinine ≤ 1.7 mg/dL
• Urine protein: creatinine ratio < 0.5 OR 24-hour urine protein < 1,000 mg
• BUN ≤ 30 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• Systolic blood pressure (BP) ≤ 160 mm Hg or diastolic BP ≤ 90 mm Hg
• No evidence of acute cardiac ischemia by electrocardiogram
• No other invasive malignancy within the past 3 years, except for nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

• No severe, active comorbidity, including any of the following:

  • Unstable angina and/or congestive heart failure within the past 6 months
  • Transmural myocardial infarction within the past 6 months
  • Evidence of recent myocardial infarction or ischemia as indicated by ST elevations of ≥ 2 mm by EKG
  • New York Heart Association class II-IV congestive heart failure requiring hospitalization within the past 12 months
  • Stroke, cerebral vascular accident, or transient ischemic attack within the past 6 months
  • Serious, inadequately controlled cardiac arrhythmia
  • Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection) or clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Serious or non-healing wound, ulcer, or bone fracture
  • Abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or significant traumatic injury within the past 28 days
  • Acute bacterial or fungal infection requiring IV antibiotics
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • AIDS based on current CDC definition
  • Active connective tissue disorders (e.g., lupus or scleroderma) that, in the opinion of the treating physician, may place the patient at high risk for radiation toxicity
  • Any other major medical illness or psychiatric impairment that, in the opinion of the investigator, would preclude study drug administration or completion of study therapy
• Recovered from prior surgery

• No prior chemotherapy or radiosensitizers for cancer of the head and neck region

  • Prior chemotherapy for a different cancer is allowed
• No prior temozolomide or bevacizumab
• No prior Gliadel wafers or any other intratumoral or intracavitary treatment
• No prior radiotherapy to the head and neck (except for T1 glottic cancer) resulting in overlap of radiotherapy fields
• More than 28 days since prior major surgical procedure or open biopsy other than craniotomy for tumor resection
• More than 30 days since prior and no concurrent treatment on another therapeutic clinical trial
• No concurrent growth factors to induce elevations in neutrophil count for the purposes of administration of temozolomide on the scheduled dosing interval; to allow treatment with temozolomide at a higher dose; or to avoid interruption of the treatment during concurrent radiotherapy
• No concurrent erythropoietin
• No concurrent tumor debulking surgery, other chemotherapy, immunotherapy, biologic therapy, or additional stereotactic boost radiotherapy
• No other concurrent investigational drugs during the "blinded phase" of the study

• Concurrent full-dose anticoagulants (e.g., warfarin or low molecular weight heparin) allowed provided both of the following criteria are met:

  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin