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

• Status: Completed
• Trial end date: 2015-02-11
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Treatments: Flucytosine

Criteria

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