Vaccine Therapy With Bevacizumab Versus Bevacizumab Alone in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery

Pre-registration (Pre-Surgery) Eligibility Criteria

* Histologic documentation: Prior histologic diagnosis of GBM at first occurrence
* Stage: First or second recurrence of GBM or gliosarcoma considered to be surgically resectable
* Prior Treatment:

  * No radiotherapy within 90 days prior to pre-registration
  * No prior treatment with any anti-angiogenic agent targeting the VEGF pathway including but not limited to bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib
  * No prior treatment with HSPPC-96 or other investigational immunotherapy
  * Must have received prior treatment with radiotherapy and temozolomide for histologically confirmed GBM at initial diagnosis
  * No tumor directed therapy for most recent progression
  * No prior Gliadel® wafers
* No clinically significant cardiovascular disease:

  * Patients with a history of hypertension must be well controlled (\<150/90) on a regimen of antihypertensive therapy.
  * History of arterial thrombotic events within the past 6 months, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medial intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) are not eligible.
  * Patients who have had a deep vein thrombosis or pulmonary embolus within the past 6 months are eligible if they are on stable therapeutic anticoagulation
  * No current New York Heart Association classification II, III or IV congestive heart failure
* No significant bleeding within the past 6 months; no bleeding diathesis or coagulopathy
* No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 12 months
* No evidence of any systemic autoimmune disease (e.g. Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency, and no immunosuppressant therapy (with the exception of dexamethasone as noted below) for any reason
* Age ≥ 18 years of age
* Karnofsky functional status rating ≥70
* No more than 16 mg dexamethasone (or equivalent) per day
* Non-pregnant and non-nursing

Registration (Post-Surgery) Eligibility Criteria

* Pre-registration eligibility criteria continue to be met
* Histologic documentation: confirmed histological diagnosis of recurrent GBM or gliosarcoma
* ≥ 90% surgical resection of recurrent GBM confirmed by central radiology review by MRI with or without gadolinium per institutional guidelines. A CT scan is allowable in place of MRI only in situations where an MRI is contraindicated (e.g., patient has a heart pacemaker, metallic devices in the eye, brain or spine, severe claustrophobia).
* ≥ 7 grams of resected tumor available for vaccine manufacture as determined by institutional pathologist
* Availability of ≥ 6 clinical vials of HSPPC-96
* Required Initial Laboratory Values:

  * Granulocytes ≥1,500/µL
  * Platelet count ≥100,000/µL
  * Total Bilirubin ≤ 2.0 x ULN
  * UPC ratio \<1 or Urine protein ≤ 1+
  * Calculated creatinine clearance ≥ 45 ml/min
  * SGOT/SGPT(AST/ALT) ≤ 2.5 x ULN
* No serious, non-healing wounds or ulcers
* At least 7 days since any minor surgery such as port placement
* No major surgical procedures, open biopsy or significant traumatic injury ≤ 28 days prior to registration or anticipation of need for elective or planned major surgical procedure during the study. Core biopsy or other minor surgical procedures ≤7 days prior to registration.
* No active or recent hemoptysis (≥½ teaspoon of bright red blood per episode) ≤ 30 days prior to registration
* No new bleeding on D28 (+/-3) MRI (or CT if MRI is contraindicated)
* No clinical deterioration at the time of registration/randomization
* If a second surgery is needed for completion of resection, this should be within 30 days from the first surgery