Inclusion Criteria

Pre-registration (Pre-Surgery) Eligibility Criteria

- Histologic documentation: Prior histologic diagnosis of GBM at first occurrence.

- Stage: First or second recurrence of GBM considered to be surgically resectable.

- Prior Treatment:

- No radiotherapy within 3 months 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

- ≥ 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).

- ≥ 9 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.