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