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

Glioblastoma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02511405
• Other study ID #: VB-111-215
• Status: Completed
• Phase: Phase 3
• Start date: August 2015
• Est. completion date: September 30, 2018

Study information

• Verified date: January 2017
• Source: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: September 30, 2018
• Est. primary completion date: November 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma

Intervention

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

Locations

Country	Name	City	State
Canada	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
Israel	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
United States	Dent Neurosciences Research Center	Amherst	New York
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Piedmont Physicians Neuro-Oncology	Atlanta	Georgia
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	University of Alabama	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	The University of Chicago	Chicago	Illinois
United States	Baylor Health Neuro-Oncology Associates	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Colorado Neurological Institute	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Florida Preston A. Wells, Jr. Center for Brain Tumor Therapy	Gainesville	Florida
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	: University of Texas, HSC	Houston	Texas
United States	MD Anderson	Houston	Texas
United States	University of California Irvine Medical Center	Irvine	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	North Shore University Hospital	Lake Success	New York
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	University of California Los Angeles	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Metro-MN Community Oncology Research Consortium	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	Derald H. Ruttenberg Treatment Center	New York	New York
United States	The Center for Cancer Prevention and Treatment	Orangevale	California
United States	Orlando Health	Orlando	Florida
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Kaiser Permanente - Redwood City Medical Center	Redwood City	California
United States	University of Rochester Medical Center	Rochester	New York
United States	Highlands Oncology Group	Rogers	Arizona
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute at The University of Utah	Salt Lake City	Utah
United States	UTHSCSA	San Antonio	Texas
United States	University of California	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	Louisiana State University Health Science Center	Shreveport	Louisiana
United States	Stanford University	Stanford	California
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	The George Washington University Medical Faculty Associates	Washington	District of Columbia
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Vascular Biogenics Ltd. operating as VBL Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		From date of study entry until the date of death from any cause (up to 10 years)
Secondary	Progression Free Survival		To be assessed from date of randomization until the date of disease progression, assessed up to 10 years.
Secondary	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.

External Links

•   VBL Therapeutics Company Website