Vaccine Therapy With Bevacizumab Versus Bevacizumab Alone in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery
Condition: Recurrent Glioblastoma; Recurrent Adult Brain Tumor; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma; Recurrence
Intervention: HSPPC-96; bevacizumab
Intervention description: intradermal infusion; intravenous
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well giving vaccine therapy with or without
      bevacizumab works in treating patients with recurrent glioblastoma multiforme that can be
      removed by surgery. Vaccines consisting of heat shock protein-peptide complexes made from a
      person's own tumor tissue may help the body build an effective immune response to kill tumor
      cells that may remain after surgery. Monoclonal antibodies, such as bevacizumab, can block
      tumor growth in different ways. Some block the ability of tumor cells to grow and spread.
      Others find tumor cells and help kill them. It is not yet known whether giving vaccine
      therapy is more effective with or without bevacizumab in treating glioblastoma multiforme.
    

Eligibility criteria:

        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