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

• Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Information provided by (Responsible Party): Vascular Biogenics Ltd. operating as VBL Therapeutics

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

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated 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 :	August 2015
Actual Primary Completion Date :	November 3, 2017
Actual Study Completion Date :	September 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 [ Time Frame: From date of study entry until the date of death from any cause (up to 10 years) ]

Secondary Outcome Measures :

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

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

  Show 57 Study Locations

Sponsors and Collaborators

Vascular Biogenics Ltd. operating as VBL Therapeutics

More Information

Additional Information:

VBL Therapeutics Company Website 

Layout table for additonal information

Responsible Party:	Vascular Biogenics Ltd. operating as VBL Therapeutics
ClinicalTrials.gov Identifier:	NCT02511405 History of Changes
Other Study ID Numbers:	VB-111-215
First Posted:	July 30, 2015
Last Update Posted:	October 23, 2018
Last Verified:	January 2017

Keywords provided by Vascular Biogenics Ltd. operating as VBL Therapeutics:

rGBM; Recurrent Glioblastoma; Recurrent GBM

Additional relevant MeSH terms:

Layout table for MeSH terms

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial	Neoplasms, Nerve Tissue; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors