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

Phase 3

Completed

• Conditions: Glioblastoma
• Interventions: Drug: Bevacizumab; Drug: VB-111 + bevacizumab

• Registration Number: NCT02511405
• Lead Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-07-29
• Study First Submitted QC: 2015-07-29
• Study First Posted: 2015-07-30
• Study Start: 2015-08
• Status Verified: 2017-01
• Primary Completion: 2017-11-03
• Study Completion: 2018-09-30
• Last Update Submitted: 2018-10-22
• Last Update Posted: 2018-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 252

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2	Bevacizumab	Bevacizumab
Arm 1	VB-111 + bevacizumab	VB-111 + Bevacizumab

Primary Outcome Measures

Name	Time	Method
Overall survival	From date of study entry until the date of death from any cause (up to 10 years)

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (57)

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Highlands Oncology Group; 🇺🇸 Rogers, Arizona, United States

University of California Irvine Medical Center; 🇺🇸 Irvine, California, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

The Center for Cancer Prevention and Treatment; 🇺🇸 Orangevale, California, United States

Kaiser Permanente - Redwood City Medical Center; 🇺🇸 Redwood City, California, United States

University of California; 🇺🇸 San Diego, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

Colorado Neurological Institute; 🇺🇸 Denver, Colorado, United States

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