RATIONALE: Genetically-modified neural stem cells (NSCs) that convert 5-fluorocytosine (5-FC) into the chemotherapy agent 5-FU (fluorouracil) at sites of tumor in the brain may be an effective treatment for glioma. PURPOSE: This clinical trial studies genetically-modified NSCs and 5-FC in patients undergoing surgery for recurrent high-grade gliomas.
PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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assess the presence of 5-FU in the brain with the use of fluorine (19F)-magnetic resonance spectroscopy (MRS)(no longer in effect as of 5/1/2012).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 tracker. 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. OUTLINE: This is a dose-escalation study. After biopsy or 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Given orally
Correlative studies
Correlative studies
Injected at the time of the surgery to resect the tumor
Correlative studies
Correlative studies
Correlative studies
Surgery to resect the tumor
Injected at the time of the surgery to resect the tumor
City of Hope
Duarte, California, United States
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
Time frame: Day 60
Relationship between intracerebral and systemic concentrations of 5-FC and 5-FU with increasing NSC dose level
Summarized by NSC dose cohort using descriptive statistics and graphs. The Macdonald Criteria will be used to assess response. As of 11/30/2012 patients will no longer undergo these tests.
Time frame: Up to Day 10
Presence of 5-FU in the brain using 19F-MRS
As of 5/1/2012, study patients will no longer undergo 19F-MRS.
Time frame: Day 60
Assessment of development of immunogenicity against NSCs
As of 11/30/2012 patients will no longer undergo these tests.
Time frame: Day 60
Obtain 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.
Time frame: Day 60
Assessment of the fate of NSCs at autopsy when feasible
Time frame: At autopsy
Assess the intracerebral distribution of NSCs using iron-labeling as a cellular tracker.
Time frame: Up to Day 10
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