Clinical Trial Finder

Inclusion Criteria:

• - Patient has had a prior, histologically-confirmed, diagnosis of a grade III or grade IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma), or has a prior, histologically-confirmed, diagnosis of a grade II glioma and now has radiographic findings consistent with a high-grade glioma (grade III or IV) - Imaging studies show evidence of recurrent supratentorial tumor(s) - The patient must be in need of a craniotomy for tumor resection or a stereotactic brain biopsy for the purpose of diagnosis or differentiating between tumor progression versus treatment-induced effects following radiation therapy +/- chemotherapy.

• - Based on the neurosurgeon's judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles.

• - Patient's high-grade glioma has recurred or progressed after chemoradiation.

• - Patient has a Karnofsky Performance Status of >= 70% - Patient has a life expectancy of >=3 months.

• - If patient requires corticosteroids for the control of cerebral edema, s/he must be on a stable dose for at least 1 week prior to enrollment.

• - Patient has recovered from toxicity of prior therapies; an interval of at least 12 weeks must have elapsed since the completion of radiation therapy; at least 6 weeks since the completion of nitrosourea-containing chemotherapy regimen; and at least 4 weeks since the completion of a non-nitrosourea-containing cytotoxic chemotherapy regimen; if a patient's most recent treatment was with a targeted agent only; and s/he has recovered from any toxicity of this targeted agent, then a waiting period of only 2 weeks is needed from the last dose and the start of study treatment, with the exception of bevacizumab where a wash out period of at least 4 weeks is required before starting study treatment.

• - Absolute neutrophil count of >= 1,500 cells/mm^3 and platelet count >= 100,000 cells/mm^3.

• - Total bilirubin =< 2.0 mg/dl.

• - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 4 times the institutional upper limit of normal.

• - Serum creatinine =< the institutional upper limit of normal.

• - Patients must be able to swallow pills.

• - Patients must be able to understand and be willing to sign a written informed consent document.

• - Female patients of child-bearing potential and sexually active male patients must agree to use an effective method of contraception while participating in this study.

• - Women of childbearing potential must have a negative pregnancy =< 2 weeks prior to registration.

INCLUSION CRITERIA FOR PROCEEDING TO TREATMENT WITH 5-FC:

• - Patients must be tolerating oral intake.

• - Patients' daily total dose of dexamethasone must be < 12 mg by Day 4.

Exclusion Criteria:

• - Patients who are currently receiving chemotherapy, radiotherapy, or are enrolled in another treatment clinical trial.

• - Patients who have anti-human leukocyte antigen (HLA) antibodies specific for HLA antigens expressed by the HB1.

F3.CD NSCs.

• - Patients who are unable to undergo an MRI.

• - Patients with chronic or active viral infections of the central nervous system (CNS) - Patients who are allergic to 5-FC or 5-FU.

• - Patients who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

• - Female patients who are pregnant or breast-feeding.

• - Patients who have not recovered from the toxicities of prior chemotherapy or radiotherapy.

- Patients who require anti-seizure medication but are not on a stable dose of anti-seizure medication for at least 1 week prior to enrollment

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.

Arms

Experimental: Arm I

Patients undergo debulking craniotomy and receive injections of HB1.F3.CD neural stem cells directly into brain tissue on day 0. Patients then receive oral 5-fluorocytosine every 6 hours on days 4-10 in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - flucytosine

Given orally

Other: - polymerase chain reaction

Correlative studies

Other: - immunohistochemistry staining method

Correlative studies

Biological: - gene therapy

Injected at the time of the surgery to resect the tumor

Other: - pharmacological study

Correlative studies

Other: - 3-Tesla magnetic resonance imaging

Correlative studies

Other: - laboratory biomarker analysis

Correlative studies

Procedure: - therapeutic conventional surgery

Surgery to resect the tumor

Biological: - E. coli CD-expressing genetically modified neural stem cells

Injected at the time of the surgery to resect the tumor