A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, ALLIANCE IND # 15380) Vaccine Given With Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM)
A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, ALLIANCE IND # 15380) Vaccine Given With Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM)
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.
The purpose of this study is to compare the effects of a vaccine with bevacizumab versus bevacizumab alone on a patient's brain tumor. The vaccine is called heat shock protein peptide complex 96 (HSPPC-96). HSPPC-96 is experimental. Specifically, HSPPC-96 is a protein that may work to help the body have a response against remaining brain tumor cells. Bevacizumab has been approved by the Food and Drug administration for treating brain tumors that grow back. In this study, patients will either get HSPPC-96 vaccine at the same time as bevacizumab, HSPPC vaccine first and then bevacizumab if the tumor comes back, or bevacizumab alone. The use of HSPPC-96 and bevacizumab is investigational.
The primary objective of the study is to determine whether there is an overall survival advantage of HSPPC-96 administered with bevacizumab, given concomitantly or at the point of progression, in comparison with bevacizumab alone in patients with surgically resectable recurrent glioblastoma multiforme.
The secondary objectives are:
Patients must undergo surgery within 28 days from pre-registration. There must be confirmation of adequacy of tissue for vaccine manufacture, tumor tissue submitted to Agenus, confirmation of ≥ 90% resection by central radiology review and vaccine manufacture of at least six vials. Patients will be randomized to one of three treatment arms. Please see the "Arms" section for more details.
Patients will be monitored approximately 5 years post-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 clinically significant cardiovascular disease:
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:
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
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