GlioblastomaPhase 3GLOBENCT02511405
A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE)
A Phase 3 study testing VB-111 + bevacizumab and Bevacizumab in people with Glioblastoma, run by Vascular Biogenics Ltd. operating as VBL Therapeutics at 57 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- VB-111 + bevacizumab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 252 participants
- Where
- 57 sitesin 3 countries
- Study dates
- Aug 2015to 30 Sep 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
57 sites in 3 countries.
57 sites in 3 countries
United States48 sites
Dent Neurosciences Research Center
Amherst, New York
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan
Piedmont Physicians Neuro-Oncology
Atlanta, Georgia
Texas Oncology-Austin Midtown
Austin, Texas, 78705
University of Alabama
Birmingham, Alabama
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
University of Virginia
Charlottesville, Virginia
Northwestern University
Chicago, Illinois
The University of Chicago
Chicago, Illinois
Baylor Health Neuro-Oncology Associates
Dallas, Texas
University of Texas Southwestern Medical Center
Dallas, Texas
Colorado Neurological Institute
Denver, Colorado
Henry Ford Health System
Detroit, Michigan
University of Florida Preston A. Wells, Jr. Center for Brain Tumor Therapy
Gainesville, Florida
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania
: University of Texas, HSC
Houston, Texas
MD Anderson
Houston, Texas
University of California Irvine Medical Center
Irvine, California
University of Kansas Medical Center
Kansas City, Kansas
North Shore University Hospital
Lake Success, New York
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire
University of Kentucky
Lexington, Kentucky
University of California Los Angeles
Los Angeles, California
University of Louisville
Louisville, Kentucky, 40202
University of Wisconsin
Madison, Wisconsin
Metro-MN Community Oncology Research Consortium
Minneapolis, Minnesota, 55416
Columbia University Medical Center
New York, New York
Derald H. Ruttenberg Treatment Center
New York, New York
The Center for Cancer Prevention and Treatment
Orangevale, California
Orlando Health
Orlando, Florida
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania
Kaiser Permanente - Redwood City Medical Center
Redwood City, California
University of Rochester Medical Center
Rochester, New York
Highlands Oncology Group
Rogers, Arizona
Huntsman Cancer Institute at The University of Utah
Salt Lake City, Utah
UTHSCSA
San Antonio, Texas
University of California
San Diego, California
University of California San Francisco
San Francisco, California
Swedish Medical Center
Seattle, Washington
Louisiana State University Health Science Center
Shreveport, Louisiana
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University
Stanford, California
Stony Brook University, Neurology Associates of Stony Brook
Stony Brook, New York
SUNY Upstate Medical University
Syracuse, New York
The George Washington University Medical Faculty Associates
Washington D.C., District of Columbia
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina
Israel5 sites
Rambam Medical Center
Haifa
Hadassah Medical Center
Jerusalem
Rabin Medical Center
Petach Tikvah
Chaim Sheba Medical Center
Ramat Gan
Tel Aviv Sourasky Medical Center
Tel Aviv
Canada4 sites
Tom Baker Cancer Centre
Calgary, Alberta
London Health Sciences Centre
London, Ontario
Ottawa Hospital
Ottawa, Ontario
Sunnybrook Health Science Centre
Toronto, Ontario
About this study
Official title: 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
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.
- Conditions
- Glioblastoma
- Being tested
- VB-111 + bevacizumab, Bevacizumab
- Keywords
- rGBM, Recurrent Glioblastoma, Recurrent GBM
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VB-111 + bevacizumabDrug
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
BevacizumabDrug
Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | VB-111 + Bevacizumab Receives: Drug: VB-111 + bevacizumab |
| Arm 2 | Active comparator | Bevacizumab Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: From date of study entry until the date of death from any cause (up to 10 years)
Secondary outcomes (2)
Progression Free Survival
Measured: 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
Measured: To be assessed from date of randomization until the date of disease progression, assessed up to 10 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2015 (estimated)
- Study startAug 2015
- Primary completion3 Nov 2017
- Study completion30 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 252 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vascular Biogenics Ltd. operating as VBL Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02511405
- Sponsor's protocol ID
- VB-111-215
- Acronym
- GLOBE
- Status last verified
- Jan 2017
- First submitted
- 29 Jul 2015
- Last updated
- 23 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37540556Cloughesy 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.
PubMed 31844890
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02511405
- Acronym / sponsor ID
- GLOBE / VB-111-215
- Conditions
- Glioblastoma
- Keywords
- rGBM, Recurrent Glioblastoma, Recurrent GBM
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 252 participants (estimated)
- Lead sponsor
- Vascular Biogenics Ltd. operating as VBL TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2015
- Primary completion
- 3 Nov 2017 (actual)
- Study completion
- 30 Sep 2018 (actual)
- First posted
- 30 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: VB-111 + bevacizumabVB-111 + Bevacizumab |
| Arm 2 | Active comparator | Drug: BevacizumabBevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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;
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VB-111 + bevacizumabVB-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 | Drug | Arm 1 |
| BevacizumabBevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks | Drug | Arm 2 |
Primary outcome
Overall survival
Time frame: From date of study entry until the date of death from any cause (up to 10 years)
2 secondary outcomes
Progression Free Survival
Time frame: 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
Time frame: To be assessed from date of randomization until the date of disease progression, assessed up to 10 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2018.
- Derived from this study: PubMed 37540556Ellingson 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.
- Derived from this study: PubMed 31844890Cloughesy 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.
- VBL Therapeutics Company WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
57 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing VB-111 + bevacizumab and Bevacizumab in people with Glioblastoma, run by Vascular Biogenics Ltd. operating as VBL Therapeutics at 57 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 57 sites in United States, Israel, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: From date of study entry until the date of death from any cause (up to 10 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02511405, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2018.