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

Study Overview
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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.

Official Title
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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

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: VB-111 + bevacizumab
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First or second progression of Glioblastoma; Measurable disease by RANO criteria at progression; Patients ≥18 years of age; Patient may have been operated for recurrence. If operated: residual and measurable disease after surgery is required; Surgery completed at least 28 days before randomization; 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; Adequate performance, i.e.Karnofsky Performance Score of at least 70%; 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: Prior anti-angiogenic therapy including VEGF sequestering agents (i.e. bevacizumab, aflibercept, etc.) or VEGFR inhibitors (cedirinib, pazopanib, sunitinib, sorafenib, etc.); Prior stereotactic radiotherapy; Pregnant or breastfeeding patients; Concomitant medication that may interfere with study results; e.g. immunosuppressive agents other than corticosteroids; Active infection; Evidence of significant CNS haemorrhage i.e. CTCAE grade 2 or above; Expected to have surgery during study period; 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); Patients with known proliferative and/or vascular retinopathy; Patients with known liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune); 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; Patients testing positive to one of the following viruses: HIV, HBV and HCV within the last 6 months; Patients that have undergone major surgery within the last 4 weeks before enrollment; Patients who have received treatment with any other investigational agent within 4 weeks before enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>VB-111 + Bevacizumab | Drug: VB-111 + bevacizumab<br>* 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<br>|
| Active Comparator: Arm 2<br>Bevacizumab | Drug: Bevacizumab<br>* Bevacizumab will be administered intravenously at a dose of 10mg/kg every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From date of study entry until the date of death from any cause (up to 10 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | To be assessed from date of randomization until the date of disease progression, assessed up to 10 years. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rGBM, Recurrent Glioblastoma, Recurrent GBM