Clinical trial NCT02511405: A Phase 3, Pivotal Trial of VB-111 Plus Bevacizumab vs. Bevacizumab in Patients With Recurrent Glioblastoma (GLOBE)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glioblastoma
Keywords: rGBM
Recurrent Glioblastoma
Recurrent GBM
Lead sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-07-30
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: From date of study entry until the date of death from any cause (up to 10 years)
Secondary outcomes:
measure: Progression Free Survival
timeFrame: To be assessed from date of randomization until the date of disease progression, assessed up to 10 years.
measure: Tumor response as measured by RANO Criteria
timeFrame: To be assessed from date of randomization until the date of disease progression, assessed up to 10 years.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arizona
city: Irvine
country: United States
facility: University of California Irvine Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Orangevale
country: United States
facility: The Center for Cancer Prevention and Treatment
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente - Redwood City Medical Center
state: California
city: San Diego
country: United States
facility: University of California
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Washington
country: United States
facility: The George Washington University Medical Faculty Associates
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Preston A. Wells, Jr. Center for Brain Tumor Therapy
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Atlanta
country: United States
facility: Piedmont Physicians Neuro-Oncology
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Metro-MN Community Oncology Research Consortium
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Amherst
country: United States
facility: Dent Neurosciences Research Center
state: New York
city: Lake Success
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Derald H. Ruttenberg Treatment Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University, Neurology Associates of Stony Brook
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Baylor Health Neuro-Oncology Associates
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: : University of Texas, HSC
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: UTHSCSA
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at The University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikvah
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
Study officials:
References:
citation: 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.