Vaccine Therapy With Bevacizumab Versus Bevacizumab Alone in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery
Recurrent Glioblastoma, Recurrent Adult Brain Tumor, Gliosarcoma
About this trial
This is an interventional treatment trial for Recurrent Glioblastoma
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
Sites / Locations
- Anchorage Associates in Radiation Medicine
- Anchorage Radiation Therapy Center
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Regional Hospital
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Mercy Cancer Center-Hot Springs
- University of Arkansas for Medical Sciences
- Kaiser Permanente-Deer Valley Medical Center
- Sutter Auburn Faith Hospital
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick Campus
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Mills - Peninsula Hospitals
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Eden Hospital Medical Center
- Sutter Davis Hospital
- Epic Care-Dublin
- Bay Area Breast Surgeons Inc
- Epic Care Partners in Cancer Care
- Kaiser Permanente-Fremont
- Fresno Cancer Center
- Kaiser Permanente
- Kaiser Permanente Los Angeles Medical Center
- Contra Costa Regional Medical Center
- Memorial Medical Center
- Kaiser Permanente-Modesto
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation-Gynecologic Oncology
- Alta Bates Summit Medical Center - Summit Campus
- Bay Area Tumor Institute
- Kaiser Permanente Oakland-Broadway
- Kaiser Permanente-Oakland
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute
- Kaiser Permanente-Rancho Cordova Cancer Center
- Kaiser Permanente-Redwood City
- Kaiser Permanente-Richmond
- Rohnert Park Cancer Center
- Kaiser Permanente-Roseville
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- The Permanente Medical Group-Roseville Radiation Oncology
- Sutter General Hospital
- Kaiser Permanente-South Sacramento
- South Sacramento Cancer Center
- Kaiser Permanente - Sacramento
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Francisco
- UCSF Medical Center-Mount Zion
- UCSF Medical Center-Parnassus
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Kaiser Permanente-San Rafael
- Kaiser Permanente Medical Center - Santa Clara
- Palo Alto Medical Foundation-Santa Cruz
- Kaiser Permanente-Santa Rosa
- Sutter Pacific Medical Foundation
- Kaiser Permanente Cancer Treatment Center
- Kaiser Permanente-South San Francisco
- Kaiser Permanente-Stockton
- Palo Alto Medical Foundation-Sunnyvale
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Kaiser Permanente Medical Center-Vacaville
- Kaiser Permanente-Vallejo
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente-Walnut Creek
- Rocky Mountain Cancer Centers-Aurora
- The Medical Center of Aurora
- Boulder Community Hospital
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Porter Adventist Hospital
- Colorado Blood Cancer Institute
- Presbyterian - Saint Lukes Medical Center - Health One
- Rocky Mountain Cancer Centers-Midtown
- SCL Health Saint Joseph Hospital
- Rocky Mountain Cancer Centers-Rose
- Rose Medical Center
- Colorado Cancer Research Program NCORP
- Mercy Medical Center
- Southwest Oncology PC
- Comprehensive Cancer Care and Research Institute of Colorado LLC
- Swedish Medical Center
- Mountain Blue Cancer Care Center
- North Colorado Medical Center
- Rocky Mountain Cancer Centers-Greenwood Village
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony Hospital
- Rocky Mountain Cancer Centers-Littleton
- Littleton Adventist Hospital
- Rocky Mountain Cancer Centers-Sky Ridge
- Sky Ridge Medical Center
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- McKee Medical Center
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- Rocky Mountain Cancer Centers - Pueblo
- Rocky Mountain Cancer Centers-Thornton
- SCL Health Lutheran Medical Center
- Saint Vincent's Medical Center
- Smilow Cancer Hospital Care Center at Saint Francis
- Boca Raton Regional Hospital
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Mount Sinai Medical Center
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Memorial Hospital West
- Emory University Hospital Midtown
- Piedmont Hospital
- Emory University/Winship Cancer Institute
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Mountain States Tumor Institute
- Kootenai Medical Center
- Saint Luke's Mountain States Tumor Institute - Fruitland
- Saint Luke's Mountain States Tumor Institute - Meridian
- Saint Luke's Mountain States Tumor Institute - Nampa
- Kootenai Cancer Center
- Kootenai Cancer Clinic
- Saint Luke's Mountain States Tumor Institute-Twin Falls
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- Rush University Medical Center
- University of Chicago Comprehensive Cancer Center
- Cancer Care Center of Decatur
- Decatur Memorial Hospital
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Northwestern Medicine Cancer Center Delnor
- NorthShore University HealthSystem-Glenbrook Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Illinois CancerCare-Ottawa Clinic
- Radiation Oncology of Northern Illinois
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Methodist Medical Center of Illinois
- Illinois CancerCare-Peoria
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- Central Illinois Hematology Oncology Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Cancer Care Specialists of Illinois-Swansea
- Northwestern Medicine Cancer Center Warrenville
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Radiation Oncology Associates PC
- Parkview Hospital Randallia
- Franciscan Health Indianapolis
- Community Howard Regional Health
- IU Health La Porte Hospital
- Memorial Regional Cancer Center Day Road
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Michiana Hematology Oncology PC-Plymouth
- Reid Health
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- South Bend Clinic
- Northern Indiana Cancer Research Consortium
- Michiana Hematology Oncology PC-Westville
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Greater Regional Medical Center
- Medical Oncology and Hematology Associates-Laurel
- Mercy Medical Center - Des Moines
- Mercy Medical Center-West Lakes
- Kansas Institute of Medicine Cancer and Blood Center
- Minimally Invasive Surgery Hospital
- Menorah Medical Center
- Saint Luke's South Hospital
- Kansas City NCI Community Oncology Research Program
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- University of Kentucky/Markey Cancer Center
- Jewish Hospital
- Norton Hospital Pavilion and Medical Campus
- Saints Mary and Elizabeth Hospital
- Jewish Hospital Medical Center Northeast
- Jewish Hospital Medical Center South
- Maine Medical Center- Scarborough Campus
- University of Maryland/Greenebaum Cancer Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Northwest Hospital Center
- Tufts Medical Center
- Massachusetts General Hospital Cancer Center
- Bixby Medical Center
- Hickman Cancer Center
- Saint Joseph Mercy Hospital
- Michigan Cancer Research Consortium NCORP
- Beaumont Hospital-Dearborn
- Saint John Hospital and Medical Center
- Hurley Medical Center
- Genesys Hurley Cancer Institute
- Allegiance Health
- Sparrow Hospital
- Saint Mary Mercy Hospital
- Marquette General Hematology Oncology
- Marquette General Hospital
- Mercy Memorial Hospital
- Toledo Clinic Cancer Centers-Monroe
- Saint Joseph Mercy Oakland
- Saint Mary's of Michigan
- Lakeland Hospital
- Marie Yeager Cancer Center
- Saint John Macomb-Oakland Hospital
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Cancer Center
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview-Southdale Hospital
- Unity Hospital
- Fairview Maple Grove Medical Center
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Health Partners Inc
- New Ulm Medical Center
- North Memorial Medical Health Center
- Mayo Clinic
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Fairview Lakes Medical Center
- University of Mississippi Medical Center
- Parkland Health Center-Bonne Terre
- Saint Francis Medical Center
- Southeast Cancer Center
- Centerpoint Medical Center LLC
- Capital Region Medical Center-Goldschmidt Cancer Center
- Saint Luke's Hospital of Kansas City
- North Kansas City Hospital
- Heartland Hematology and Oncology Associates Incorporated
- Research Medical Center
- Saint Luke's East - Lee's Summit
- Liberty Radiation Oncology Center
- Heartland Regional Medical Center
- Saint Joseph Oncology Inc
- Washington University School of Medicine
- Missouri Baptist Medical Center
- Sainte Genevieve County Memorial Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Community Hospital of Anaconda
- Billings Clinic Cancer Center
- Montana Cancer Consortium NCORP
- Saint Vincent Healthcare
- Frontier Cancer Center and Blood Institute-Billings
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Saint Peter's Community Hospital
- Kalispell Regional Medical Center
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- Community Medical Hospital
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Nebraska Cancer Research Center
- Saint Elizabeth Regional Medical Center
- Missouri Valley Cancer Consortium
- Alegent Health Immanuel Medical Center
- Hemotology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- University of Nebraska Medical Center
- Midlands Community Hospital
- Dartmouth Hitchcock Medical Center
- Hackensack University Medical Center
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Rutgers Cancer Institute of New Jersey
- The Valley Hospital-Luckow Pavilion
- Neurosurgeons of New Jersey-Ridgewood
- Valley Hospital
- Valley Health System-Hematology/Oncology
- Columbia University/Herbert Irving Cancer Center
- University of Rochester
- UNC Lineberger Comprehensive Cancer Center
- Duke University Medical Center
- East Carolina University
- Wake Forest University Health Sciences
- Altru Cancer Center
- Toledo Clinic Cancer Centers-Bowling Green
- University of Cincinnati/Barrett Cancer Center
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Case Western Reserve University
- Ohio State University Comprehensive Cancer Center
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Samaritan North Health Center
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Lima Memorial Hospital
- Toledo Clinic Cancer Centers-Maumee
- Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- Flower Hospital
- Mercy Hospital of Tiffin
- The Toledo Hospital/Toledo Children's Hospital
- Saint Vincent Mercy Medical Center
- University of Toledo
- Mercy Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Upper Valley Medical Center
- Fulton County Health Center
- University Pointe
- Greene Memorial Hospital
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Oncology and Hematology Care Southeast
- Bay Area Hospital
- Legacy Mount Hood Medical Center
- Providence Milwaukie Hospital
- Providence Newberg Medical Center
- Providence Willamette Falls Medical Center
- Legacy Good Samaritan Hospital and Medical Center
- Providence Portland Medical Center
- Providence Saint Vincent Medical Center
- Legacy Meridian Park Hospital
- Lehigh Valley Hospital-Cedar Crest
- Lehigh Valley Hospital - Muhlenberg
- University of Pittsburgh Cancer Institute (UPCI)
- Avera Cancer Institute
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- Memorial GYN Plus
- Saint Joseph Regional Cancer Center
- Huntsman Cancer Institute/University of Utah
- Inova Fairfax Hospital
- Fredericksburg Oncology Inc
- Sentara Norfolk General Hospital
- Providence Regional Cancer System-Aberdeen
- Cancer Care Center at Island Hospital
- Swedish Cancer Institute-Eastside Oncology Hematology
- PeaceHealth Saint Joseph Medical Center
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Providence Regional Cancer System-Centralia
- Swedish Medical Center-Edmonds
- Saint Elizabeth Hospital
- Providence Regional Cancer Partnership
- Saint Francis Hospital
- Swedish Cancer Institute-Issaquah
- Providence Regional Cancer System-Lacey
- Saint Clare Hospital
- PeaceHealth Saint John Medical Center
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- Minor and James Medical PLLC
- Pacific Gynecology Specialists
- Swedish Medical Center-Ballard Campus
- Group Health Cooperative-Seattle
- Swedish Medical Center-First Hill
- Providence Regional Cancer System-Shelton
- Rockwood Clinic Cancer Treatment Center-Valley
- Rockwood Cancer Treatment Center-DHEC-Downtown
- Evergreen Hematology and Oncology PS
- Franciscan Research Center-Northwest Medical Plaza
- Northwest Medical Specialties PLLC
- PeaceHealth Southwest Medical Center
- Compass Oncology Vancouver
- Legacy Salmon Creek Hospital
- Providence Saint Mary Regional Cancer Center
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
- Providence Regional Cancer System-Yelm
- University of Wisconsin Hospital and Clinics
- Aurora Saint Luke's Medical Center
- Cancer Center of Western Wisconsin
- Aurora Cancer Care-Racine
- Cheyenne Regional Medical Center-West
- Big Horn Basin Cancer Center
- Billings Clinic-Cody
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Arm 1, HSPPC-96 + concomitant bevacizumab
Arm 2, HSPPC-96 with bevacizumab at progression
Arm 3, Bevacizumab
HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression.
HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days) NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine.
Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days)