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

Inclusion Criteria:

• Histologically proven diagnosis of glioblastoma or gliosarcoma (World HealthOrganization [WHO] grade IV) confirmed by central review prior to step 2 registration

• Tumor tissue that is determined by central pathology review prior to step 2registration to be of sufficient size for analysis of O-6-methylguanine-DNAmethyltransferase (MGMT) and determination of molecular profile

• Patients must have at least 1 block of tumor tissue; submission of 2 blocks isstrongly encouraged to maximize the chances of eligibility; at least 1 cubiccentimeter of tissue composed primarily of tumor must be present

• CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; freshfrozen tumor tissue acquisition is encouraged

• Diagnosis must be made by surgical excision, either partial or complete;stereotactic biopsy is not allowed because it will not provide sufficient tissuefor MGMT analysis

• The tumor tissue should be sent as soon as possible to maximize the likelihood ofeligibility; tumor tissue should be submitted by 4 weeks after the surgicalprocedure so that the study registration and treatment can commence by themandatory 5 week post-surgery outer limit

• Sites must submit tissue fir central review in order to obtain the MGMT analysis;patients from sites not following protocol-specified process for obtaining MGMTresults will be made ineligible

• The tumor must have a supratentorial component

• History/physical examination within 14 days prior to step 2 registration

• The patient must have recovered from the effects of surgery, postoperative infection,and other complications before step 2 registration

• A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively andpostoperatively prior to the initiation of radiotherapy; the postoperative scan mustbe performed within 28 days prior to step 1 registration

• An MRI or computed tomography (CT) scan (potentially in addition to thepostoperative scan) must be obtained within 10 days prior to the start ofradiation therapy and must not demonstrate significant postoperative hemorrhagedefined as > 1 cm diameter of blood; if > 1 cm of acute blood is detected, thepatient will be ineligible for this trial; the radiation planning MRI or CT scanmay be used to determine presence of hemorrhage

• Patients unable to undergo MR imaging because of non-compatible devices can beenrolled, provided pre- and postoperative contrast-enhanced CT scans are obtainedand are of sufficient quality; preoperative and postoperative scans must be thesame type; such patients cannot be enrolled into the advanced imaging component

• Documentation of steroid doses within 14 days prior to step 2 registration

• Karnofsky performance status >= 70

• Absolute neutrophil count (ANC) >= 1,800 cells/mm^3

• Platelets >= 100,000 cells/mm^3

• Hemoglobin >= 10.0 g/dL (Note: the use of transfusion or other intervention to achievehemoglobin [Hgb] >= 10.0 g/dl is acceptable)

• Blood urea nitrogen (BUN) =< 30 mg/dL within 14 days prior to step 2 registration

• Creatinine =< 1.7 mg/dl within 14 days prior to step 2 registration

• Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; forUPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg

• Bilirubin =< 2.0 mg/dl within 14 days prior to step 2 registration

• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x normal rangewithin 14 days prior to step 2 registration

• Systolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mm Hg within 14 daysprior to step 2 registration

• Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior tostep 2 registration

• Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not onwarfarin confirmed by testing within 14 days prior to step 2 registration

• Patients on full-dose anticoagulants (e.g., warfarin or low molecular weight [LMW]heparin) must meet both of the following criteria:

• 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 astable dose of LMW heparin

• Patient must provide study specific informed consent prior to study entry

• Women of childbearing potential and male participants must practice adequatecontraception

• For females of child-bearing potential, negative serum pregnancy test within 14 daysprior to step 2 registration

Exclusion Criteria:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless diseasefree for >= 3 years; (for example, carcinoma in situ of the breast, oral cavity, andcervix are all permissible)

• Recurrent or multifocal malignant gliomas

• Metastases detected below the tentorium or beyond the cranial vault

• Prior chemotherapy or radiosensitizers for cancers of the head and neck region; notethat prior chemotherapy for a different cancer is allowable, except prior temozolomideor bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitarytreatment are not permitted

• Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting inoverlap of radiation fields

• Severe, active co-morbidity, defined as follows:

• Unstable angina and/or congestive heart failure within the last 6 months

• Transmural myocardial infarction within the last 6 months

• Evidence of recent myocardial infarction or ischemia by the findings of S-Televations of >= 2 mm using the analysis of an electrocardiogram (EKG) performedwithin 14 days of step 2 registration

• New York Heart Association grade II or greater congestive heart failure requiringhospitalization within 12 months prior to step 2 registration

• History of stroke, cerebral vascular accident (CVA) or transient ischemic attackwithin 6 months

• Serious and inadequately controlled cardiac arrhythmia

• Significant vascular disease (e.g., aortic aneurysm, history of aorticdissection) or clinically significant peripheral vascular disease

• Evidence of bleeding diathesis or coagulopathy

• Serious or non-healing wound, ulcer, or bone fracture or history of abdominalfistula, gastrointestinal perforation, intra-abdominal abscess major surgicalprocedure, open biopsy, or significant traumatic injury within 28 days prior tostep 2 registration, with the exception of the craniotomy for tumor resection

• Acute bacterial or fungal infection requiring intravenous antibiotics at the timeof registration

• Chronic obstructive pulmonary disease exacerbation or other respiratory illnessrequiring hospitalization or precluding study therapy at the time of step 2registration

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;note, however, that laboratory tests for liver function and coagulationparameters are not required for entry into this protocol

• Acquired immune deficiency syndrome (AIDS) based upon current Center for DiseaseControl (CDC) definition; note, however, that HIV testing is not required forentry into this protocol; the need to exclude patients with AIDS from thisprotocol is necessary because the treatments involved in this protocol may besignificantly immunosuppressive

• Active connective tissue disorders, such as lupus or scleroderma, that in theopinion of the treating physician may put the patient at high risk for radiationtoxicity

• Any other major medical illnesses or psychiatric impairments that in theinvestigator's opinion will prevent administration or completion of protocoltherapy

• Pregnancy or women of childbearing potential and men who are sexually active and notwilling/able to use medically acceptable forms of contraception

• Pregnant or lactating women

• Patients treated on any other therapeutic clinical protocols within 30 days prior tostudy entry or during participation in the study

• For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging:inability to undergo MRI (e.g., due to safety reasons, such as presence of apacemaker)