Clinical Trials for Adults | A Phase I/II Single-Arm Open-Label Multicenter Study of VB-111 in Patients with Recurrent Glioblastoma Multiform
- The primary objective is to evaluate the safety, tolerability, and efficacy of a single dose of VB-111, in patients with relapsed glioblastoma(GBM).
- The secondary objective is to evaluate the distribution of VB-111 after a single IV infusion and the level of antibodies to the adenovirus vector and transgene.
VB-111 is a vascular disruptive agent based on an adenovirus vector. It is a non-replicating adenovector (Ad5, E1 deleted), which contains a proprietary modified murine pre-proendothelin promotor and a Fas-Chimera transgene. The modified murine promotor is able to specifically target the expression of the Fas Chimera transgene to target apoptosis (cell death) of angiogenic blood vessels that surround the tumor.
Subjects must have a histologically confirmed diagnosis of glioblastoma or gliosarcoma.
- Measurable disease
- Subjects ≥18 years of age
- Disease progression or recurrence following standard of care treatment with temozolomide and radiation
- An interval of at least 4 weeks between prior surgical resection and study enrollment
- An interval of at least 12 weeks between prior radiotherapy or at least 4 weeks from prior chemotherapy
- Karnofsky performance status ≥ 60%
- Adequate renal, liver, and bone marrow function according to the following 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
- Evidence of CNS hemorrhage CTCAE grade 2 or above on baseline MRI
- Requires therapeutic anti-coagulation
- Expected to have surgery during study period
- Subjects who suffered from an acute cardiac event within the last 12 months
- Subjects 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)
- Subjects with known proliferative and/or vascular retinopathy
- Subjects with known liver disease (alcoholic, drug/toxin induced, genetic, or autoimmune)
- Subjects that have undergone major surgery within the last 4 weeks before enrollment
This is an open label, dose escalating, multi-center, Phase I-2 study, measuring the safety, tolerability, distribution, and efficacy of a single dose of intravenously administered VB-111 in patients with relapsed GBM.
VB-111 will be administered as a single intravenous infusion of 1x10.12th or 3x10.12th . Eligible, consenting patients will be enrolled into one of three sequential dosing cohorts as follows:
Cohort VB-111 (vp) Patients No.
1 1x1012 3-6
2 3x1012 3-6
3 3x1012 23-26