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

• Status: Completed
• Trial end date: 2018-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics
• Treatments: Bevacizumab

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.