A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE)

NCT ID: NCT02511405

Last Updated: 2018-10-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

252 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2018-09-30

Brief Summary

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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

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Conditions

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Glioblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

VB-111 + Bevacizumab

Group Type EXPERIMENTAL

VB-111 + bevacizumab

Intervention Type DRUG

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

Arm 2

Bevacizumab

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks

Interventions

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VB-111 + bevacizumab

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

Intervention Type DRUG

Bevacizumab

Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. First or second progression of Glioblastoma;
2. Measurable disease by RANO criteria at progression;
3. Patients ≥18 years of age;
4. Patient may have been operated for recurrence. If operated: residual and measurable disease after surgery is required;
5. Surgery completed at least 28 days before randomization;
6. 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;
7. Adequate performance, i.e."Karnofsky Performance Score" of at least 70%;
8. 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.

Exclusion Criteria

1. Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab, aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib, etc.);
2. Prior stereotactic radiotherapy;
3. Pregnant or breastfeeding patients;
4. Concomitant medication that may interfere with study results; e.g. immunosuppressive agents other than corticosteroids;
5. Active infection;
6. Evidence of significant CNS haemorrhage i.e. CTCAE grade 2 or above;
7. Expected to have surgery during study period;
8. 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);
9. Patients with known proliferative and/or vascular retinopathy;
10. Patients with known liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune);
11. 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;
12. Patients testing positive to one of the following viruses: HIV, HBV and HCV within the last 6 months;
13. Patients that have undergone major surgery within the last 4 weeks before enrollment;
14. Patients who have received treatment with any other investigational agent within 4 weeks before enrollment.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vascular Biogenics Ltd. operating as VBL Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Highlands Oncology Group

Rogers, Arizona, United States

Site Status

University of California Irvine Medical Center

Irvine, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

The Center for Cancer Prevention and Treatment

Orangevale, California, United States

Site Status

Kaiser Permanente - Redwood City Medical Center

Redwood City, California, United States

Site Status

University of California

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Colorado Neurological Institute

Denver, Colorado, United States

Site Status

The George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, United States

Site Status

University of Florida Preston A. Wells, Jr. Center for Brain Tumor Therapy

Gainesville, Florida, United States

Site Status

Orlando Health

Orlando, Florida, United States

Site Status

Piedmont Physicians Neuro-Oncology

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Louisiana State University Health Science Center

Shreveport, Louisiana, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Metro-MN Community Oncology Research Consortium

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Dent Neurosciences Research Center

Amherst, New York, United States

Site Status

North Shore University Hospital

Lake Success, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Derald H. Ruttenberg Treatment Center

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Stony Brook University, Neurology Associates of Stony Brook

Stony Brook, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Texas Oncology-Austin Midtown

Austin, Texas, United States

Site Status

Baylor Health Neuro-Oncology Associates

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

: University of Texas, HSC

Houston, Texas, United States

Site Status

MD Anderson

Houston, Texas, United States

Site Status

UTHSCSA

San Antonio, Texas, United States

Site Status

Huntsman Cancer Institute at The University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

Sunnybrook Health Science Centre

Toronto, Ontario, Canada

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Hadassah Medical Center

Jerusalem, , Israel

Site Status

Rabin Medical Center

Petach Tikvah, , Israel

Site Status

Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Countries

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United States Canada Israel

References

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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.

Reference Type DERIVED
PMID: 37540556 (View on PubMed)

Cloughesy 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.

Reference Type DERIVED
PMID: 31844890 (View on PubMed)

Related Links

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http://www.vblrx.com

VBL Therapeutics Company Website

http://www.globetrial.com/

The Official Globe Trial Website

Other Identifiers

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VB-111-215

Identifier Type: -

Identifier Source: org_study_id

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