A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE)
- Registration Number
- NCT02511405
- Lead Sponsor
- Vascular Biogenics Ltd. operating as VBL Therapeutics
- Brief Summary
The purpose of this pivotal, phase 3, randomized, multicenter study is to compare VB-111 plus bevacizumab to bevacizumab in adult patients with recurrent Glioblastoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 252
-
First or second progression of Glioblastoma;
-
Measurable disease by RANO criteria at progression;
-
Patients ≥18 years of age;
-
Patient may have been operated for recurrence. If operated: residual and measurable disease after surgery is required;
-
Surgery completed at least 28 days before randomization;
-
An interval of at least 12 weeks between prior radiotherapy or at least 23 days from prior chemotherapy, 42 days from nitrosoureas and enrollment in this study;
-
Adequate performance, i.e."Karnofsky Performance Score" of at least 70%;
-
Adequate renal, liver, and bone marrow function according to the following criteria:
- Absolute neutrophil count ≥1500 cells/ml,
- Platelets ≥ 100,000 cells/ml,
- Total bilirubin within upper limit of normal (ULN),
- Aspartate aminotransferase (AST) ≤ 2.0 X ULN,
- Serum creatinine level ≤ ULN or creatinine clearance ≥ 50 ml/min for patients with creatinine levels above normal limits (creatinine clearance calculated by the Cockcroft-Gault formula, see Appendix II),
- PT, PTT (in seconds) not to be prolonged beyond >20% of the upper limits of normal.
- Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab, aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib, etc.);
- Prior stereotactic radiotherapy;
- Pregnant or breastfeeding patients;
- Concomitant medication that may interfere with study results; e.g. immunosuppressive agents other than corticosteroids;
- Active infection;
- Evidence of significant CNS haemorrhage i.e. CTCAE grade 2 or above;
- Expected to have surgery during study period;
- Patients with active vascular disease, either myocardial or peripheral (i.e. acute coronary syndrome, cerebral stroke, transient ischemic attack or arterial thrombosis or symptomatic peripheral vascular disease within the past 3 months);
- Patients with known proliferative and/or vascular retinopathy;
- Patients with known liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune);
- Patients with known active second malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Patients are not considered to have a currently active malignancy if they have completed anticancer therapy and have been disease free for greater than 2 years prior to screening;
- Patients testing positive to one of the following viruses: HIV, HBV and HCV within the last 6 months;
- Patients that have undergone major surgery within the last 4 weeks before enrollment;
- Patients who have received treatment with any other investigational agent within 4 weeks before enrollment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 Bevacizumab Bevacizumab Arm 1 VB-111 + bevacizumab VB-111 + Bevacizumab
- Primary Outcome Measures
Name Time Method Overall survival From date of study entry until the date of death from any cause (up to 10 years)
- Secondary Outcome Measures
Name Time Method Progression Free Survival To be assessed from date of randomization until the date of disease progression, assessed up to 10 years. Tumor response as measured by RANO Criteria To be assessed from date of randomization until the date of disease progression, assessed up to 10 years.
Trial Locations
- Locations (57)
Kaiser Permanente - Redwood City Medical Center
🇺🇸Redwood City, California, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
The University of Chicago
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
The George Washington University Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Derald H. Ruttenberg Treatment Center
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Stony Brook University, Neurology Associates of Stony Brook
🇺🇸Stony Brook, New York, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Louisiana State University Health Science Center
🇺🇸Shreveport, Louisiana, United States
: University of Texas, HSC
🇺🇸Houston, Texas, United States
Baylor Health Neuro-Oncology Associates
🇺🇸Dallas, Texas, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
North Shore University Hospital
🇺🇸Lake Success, New York, United States
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Sunnybrook Health Science Centre
🇨🇦Toronto, Ontario, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Metro-MN Community Oncology Research Consortium
🇺🇸Minneapolis, Minnesota, United States
University of California
🇺🇸San Diego, California, United States
UTHSCSA
🇺🇸San Antonio, Texas, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Huntsman Cancer Institute at The University of Utah
🇺🇸Salt Lake City, Utah, United States
Colorado Neurological Institute
🇺🇸Denver, Colorado, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
The Center for Cancer Prevention and Treatment
🇺🇸Orangevale, California, United States
Hadassah Medical Center
🇮🇱Jerusalem, Israel
MD Anderson
🇺🇸Houston, Texas, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Highlands Oncology Group
🇺🇸Rogers, Arizona, United States
University of California Irvine Medical Center
🇺🇸Irvine, California, United States
Stanford University
🇺🇸Stanford, California, United States
Piedmont Physicians Neuro-Oncology
🇺🇸Atlanta, Georgia, United States
Dent Neurosciences Research Center
🇺🇸Amherst, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Rambam Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petach Tikvah, Israel
Orlando Health
🇺🇸Orlando, Florida, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Florida Preston A. Wells, Jr. Center for Brain Tumor Therapy
🇺🇸Gainesville, Florida, United States
Texas Oncology-Austin Midtown
🇺🇸Austin, Texas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States