A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas
I. To determine the safety and feasibility of intracerebral administration of NSCs in
combination with oral 5-FC in patients with recurrent high-grade gliomas.
I. To characterize the relationship between intracerebral and systemic concentrations of
5-FC and 5-FU with increasing NSC dose level.
II. To non-invasively assess the presence of 5-FU in the brain with the use of fluorine
(19F)-magnetic resonance spectroscopy (MRS)(no longer in effect as of 5/1/2012).
III. To assess for the possible development of immunogenicity against the NSCs.
IV. To assess the intracerebral distribution of NSCs using iron-labeling as a cellular
V. To gather preliminary imaging data regarding perfusion permeability parameters and
imaging characteristics as shown on magnetic resonance imaging (MRI) studies due to the
presence of NSCs in the brain.
VI. To determine, at time of autopsy, the fate of the NSCs.
This is a dose-escalation study.
At the time of surgery to resect tumor, study patients receive injections of genetically
modified NSCs directly into brain tissue on day 0. Patients then take oral 5-FC every 6
hours during days 4-10 which is converted to 5-FU in the brain by the NSCs.
Follow-up MRIs of the brain are performed on days 32, 60, and every 2 months thereafter to
assess for response and side effects.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determination of the safety and feasibility of intracerebral administration of genetically-modified neural stem cells (NSCs) in combination with oral 5-fluorocytosine.
Measures of feasibility include the incidence of clinically symptomatic intratumoral hemorrhage, CNS infection, seizures, altered mental status, development of focal neurologic deficits, as well as chemotherapy-associated toxicities. All toxicities at each dose level will be summarized using descriptive statistics. Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Beckman Research Institute
United States: Food and Drug Administration
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