Radiosurgery Plus Bevacizumab in Glioblastoma

This is an interventional treatment trial for Glioblastoma focused on measuring adult giant cell glioblastoma, adult gliosarcoma, recurrent adult brain tumor Read More

Inclusion

• Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) at primary or subsequent resection
• Radiographic evidence of tumor progression as defined by a contrast enhanced MRI at least 3 months after the completion of radiation therapy
• Unifocal enhancing disease; the enhancing focus must be =< 3 cm in maximum diameter
• History/physical examination within 14 days prior to registration
• The patient must have recovered from the effects of prior therapy before study entry
• The patient must not have received chemotherapy within the following time frames: Non-cytotoxic agents: 2 weeks, cytotoxic agents: 3 weeks, nitrosoureas: 6 weeks
• Must be able to undergo MRI imaging
• Documentation of steroid doses within 14 days prior to registration
• Karnofsky performance status > 60
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Platelets >= 100,000 cells/mm^3
• Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >= 10.0 g/dl is acceptable)
• BUN =< 30 mg/dl within 14 days prior to study entry
• Creatinine =< 1.7 mg/dl within 14 days prior to study entry
• Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC 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 study entry
• ALT/AST =< 3 x normal range within 14 days prior to study entry
• Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior study entry
• Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin confirmed by testing within 14 days prior to study entry
• Patients on full-dose anticoagulants (e.g., warfarin or 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 a stable dose of low molecular weight heparin
• Patients must provide study specific informed consent prior to study entry
• Women of childbearing potential and male participants must practice adequate contraception
• For females of child-bearing potential, negative serum pregnancy test within 14 days prior to entry

Exclusion

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for >= 3 years (for example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
• More than one focus of enhancement
• Involvement of the brainstem (defined as the midbrain or lower)
• Prior use of chemotherapy wafers or any other intratumoral or intracavitary treatment are not permitted; prior radiosurgery is not permitted
• Prior treatment with intravenous bevacizumab
• 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-T elevations of >= 2 mm using the analysis of an EKG performed within 14 days of entry
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration
• History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months
• Serious and inadequately controlled cardiac arrhythmia
• Uncontrolled hypertension
• Significant vascular disease (e.g., aortic aneurysm, 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 or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of entry
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of entry
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
• Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol
• Active connective tissue disorders, such as lupus or scleroderma that in the opinion of the treating physician may put the patient at high risk for radiation toxicity
• Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant due to study drug
• Patients treated on any other therapeutic clinical trials within 30 days prior to study entry or during participation in the study
• Growth factors are not permitted to induce elevations in neutrophil count for the purposes of: 1) administration of temozolomide on the scheduled dosing interval; 2) allowing treatment with temozolomide at a higher dose; or 3) avoiding interruption of the treatment during concomitant radiotherapy
• No other investigational drugs will be allowed during this study
• Surgical procedures for tumor debulking, other types of chemotherapy, and immunotherapy or biologic therapy must not be used
• Additional stereotactic boost radiotherapy is not allowed