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

• Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02511405
• Collaborator: (none)
• Enrollment: 252
• Locations: 57
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma	Drug: VB-111 + bevacizumab; Drug: Bevacizumab	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 252 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Aug 1, 2015
• Actual Primary Completion Date: Nov 3, 2017
• Actual Study Completion Date: Sep 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 VB-111 + Bevacizumab	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
Active Comparator: Arm 2 Bevacizumab	Drug: Bevacizumab; Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks

Outcome Measures

Primary Outcome Measures

1. Overall survival [From date of study entry until the date of death from any cause (up to 10 years)]

Secondary Outcome Measures

1. Progression Free Survival [To be assessed from date of randomization until the date of disease progression, assessed up to 10 years.]

2. 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.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States
2	Highlands Oncology Group	Rogers	Arizona	United States
3	University of California Irvine Medical Center	Irvine	California	United States
4	University of California Los Angeles	Los Angeles	California	United States
5	The Center for Cancer Prevention and Treatment	Orangevale	California	United States
6	Kaiser Permanente - Redwood City Medical Center	Redwood City	California	United States
7	University of California	San Diego	California	United States
8	University of California San Francisco	San Francisco	California	United States
9	Stanford University	Stanford	California	United States
10	Colorado Neurological Institute	Denver	Colorado	United States
11	The George Washington University Medical Faculty Associates	Washington	District of Columbia	United States
12	University of Florida Preston A. Wells, Jr. Center for Brain Tumor Therapy	Gainesville	Florida	United States
13	Orlando Health	Orlando	Florida	United States
14	Piedmont Physicians Neuro-Oncology	Atlanta	Georgia	United States
15	Northwestern University	Chicago	Illinois	United States
16	The University of Chicago	Chicago	Illinois	United States
17	University of Kansas Medical Center	Kansas City	Kansas	United States
18	University of Kentucky	Lexington	Kentucky	United States
19	University of Louisville	Louisville	Kentucky	United States	40202
20	Louisiana State University Health Science Center	Shreveport	Louisiana	United States
21	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States
22	Dana Farber Cancer Institute	Boston	Massachusetts	United States
23	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States
24	Henry Ford Health System	Detroit	Michigan	United States
25	Metro-MN Community Oncology Research Consortium	Minneapolis	Minnesota	United States	55416
26	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
27	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States
28	Dent Neurosciences Research Center	Amherst	New York	United States
29	North Shore University Hospital	Lake Success	New York	United States
30	Columbia University Medical Center	New York	New York	United States
31	Derald H. Ruttenberg Treatment Center	New York	New York	United States
32	University of Rochester Medical Center	Rochester	New York	United States
33	Stony Brook University, Neurology Associates of Stony Brook	Stony Brook	New York	United States
34	SUNY Upstate Medical University	Syracuse	New York	United States
35	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States
36	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States
37	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States
38	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States
39	Texas Oncology-Austin Midtown	Austin	Texas	United States	78705
40	Baylor Health Neuro-Oncology Associates	Dallas	Texas	United States
41	University of Texas Southwestern Medical Center	Dallas	Texas	United States
42	: University of Texas, HSC	Houston	Texas	United States
43	MD Anderson	Houston	Texas	United States
44	UTHSCSA	San Antonio	Texas	United States
45	Huntsman Cancer Institute at The University of Utah	Salt Lake City	Utah	United States
46	University of Virginia	Charlottesville	Virginia	United States
47	Swedish Medical Center	Seattle	Washington	United States
48	University of Wisconsin	Madison	Wisconsin	United States
49	Tom Baker Cancer Centre	Calgary	Alberta	Canada
50	London Health Sciences Centre	London	Ontario	Canada
51	Ottawa Hospital	Ottawa	Ontario	Canada
52	Sunnybrook Health Science Centre	Toronto	Ontario	Canada
53	Rambam Medical Center	Haifa		Israel
54	Hadassah Medical Center	Jerusalem		Israel
55	Rabin Medical Center	Petach Tikvah		Israel
56	Chaim Sheba Medical Center	Ramat Gan		Israel
57	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel

Sponsors and Collaborators

• Vascular Biogenics Ltd. operating as VBL Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• VBL Therapeutics Company Website

Publications

None provided.

• Responsible Party: Vascular Biogenics Ltd. operating as VBL Therapeutics
• ClinicalTrials.gov Identifier: NCT02511405
• Other Study ID Numbers: VB-111-215
• First Posted: Jul 30, 2015
• Last Update Posted: Oct 23, 2018
• Last Verified: Jan 1, 2017

• Keywords provided by Vascular Biogenics Ltd. operating as VBL Therapeutics: rGBM; Recurrent Glioblastoma; Recurrent GBM
• Additional relevant MeSH terms: Glioblastoma; Bevacizumab

Study Results

No Results Posted as of Oct 23, 2018