A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE)
GLOBE
A Phase 3, Randomized, Controlled, Double-Arm, Open-Label, Multi-center Study of VB-111 Combined With Bevacizumab vs. Bevacizumab Monotherapy in Patients With Recurrent Glioblastoma
1 other identifier
interventional
252
3 countries
57
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2015
Typical duration for phase_3
57 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 29, 2015
CompletedFirst Posted
Study publicly available on registry
July 30, 2015
CompletedStudy Start
First participant enrolled
August 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 3, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2018
CompletedOctober 23, 2018
January 1, 2017
2.3 years
July 29, 2015
October 22, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall survival
From date of study entry until the date of death from any cause (up to 10 years)
Secondary Outcomes (2)
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.
Study Arms (2)
Arm 1
EXPERIMENTALVB-111 + Bevacizumab
Arm 2
ACTIVE COMPARATORBevacizumab
Interventions
VB-111 will be administered intravenously at a dose of 1x10e13 VPs every 2 months Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks
Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (57)
University of Alabama
Birmingham, Alabama, United States
Highlands Oncology Group
Rogers, Arizona, United States
University of California Irvine Medical Center
Irvine, California, United States
University of California Los Angeles
Los Angeles, California, United States
The Center for Cancer Prevention and Treatment
Orangevale, California, United States
Kaiser Permanente - Redwood City Medical Center
Redwood City, California, United States
University of California
San Diego, California, United States
University of California San Francisco
San Francisco, California, United States
Stanford University
Stanford, California, United States
Colorado Neurological Institute
Denver, Colorado, United States
The George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
University of Florida Preston A. Wells, Jr. Center for Brain Tumor Therapy
Gainesville, Florida, United States
Orlando Health
Orlando, Florida, United States
Piedmont Physicians Neuro-Oncology
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
The University of Chicago
Chicago, Illinois, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
University of Kentucky
Lexington, Kentucky, United States
University of Louisville
Louisville, Kentucky, 40202, United States
Louisiana State University Health Science Center
Shreveport, Louisiana, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Henry Ford Health System
Detroit, Michigan, United States
Metro-MN Community Oncology Research Consortium
Minneapolis, Minnesota, 55416, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
Dent Neurosciences Research Center
Amherst, New York, United States
North Shore University Hospital
Lake Success, New York, United States
Columbia University Medical Center
New York, New York, United States
Derald H. Ruttenberg Treatment Center
New York, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Stony Brook University, Neurology Associates of Stony Brook
Stony Brook, New York, United States
SUNY Upstate Medical University
Syracuse, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Texas Oncology-Austin Midtown
Austin, Texas, 78705, United States
Baylor Health Neuro-Oncology Associates
Dallas, Texas, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
: University of Texas, HSC
Houston, Texas, United States
MD Anderson
Houston, Texas, United States
UTHSCSA
San Antonio, Texas, United States
Huntsman Cancer Institute at The University of Utah
Salt Lake City, Utah, United States
University of Virginia
Charlottesville, Virginia, United States
Swedish Medical Center
Seattle, Washington, United States
University of Wisconsin
Madison, Wisconsin, United States
Tom Baker Cancer Centre
Calgary, Alberta, Canada
London Health Sciences Centre
London, Ontario, Canada
Ottawa Hospital
Ottawa, Ontario, Canada
Sunnybrook Health Science Centre
Toronto, Ontario, Canada
Rambam Medical Center
Haifa, Israel
Hadassah Medical Center
Jerusalem, Israel
Rabin Medical Center
Petach Tikvah, Israel
Chaim Sheba Medical Center
Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel
Related Publications (2)
Ellingson BM, Hagiwara A, Morris CJ, Cho NS, Oshima S, Sanvito F, Oughourlian TC, Telesca D, Raymond C, Abrey LE, Garcia J, Aftab DT, Hessel C, Rachmilewitz Minei T, Harats D, Nathanson DA, Wen PY, Cloughesy TF. Depth of Radiographic Response and Time to Tumor Regrowth Predicts Overall Survival Following Anti-VEGF Therapy in Recurrent Glioblastoma. Clin Cancer Res. 2023 Oct 13;29(20):4186-4195. doi: 10.1158/1078-0432.CCR-23-1235.
PMID: 37540556DERIVEDCloughesy TF, Brenner A, de Groot JF, Butowski NA, Zach L, Campian JL, Ellingson BM, Freedman LS, Cohen YC, Lowenton-Spier N, Rachmilewitz Minei T, Fain Shmueli S; GLOBE Study Investigators; Wen PY. A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE). Neuro Oncol. 2020 May 15;22(5):705-717. doi: 10.1093/neuonc/noz232.
PMID: 31844890DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 29, 2015
First Posted
July 30, 2015
Study Start
August 1, 2015
Primary Completion
November 3, 2017
Study Completion
September 30, 2018
Last Updated
October 23, 2018
Record last verified: 2017-01