Status:
COMPLETED
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
Lead Sponsor:
City of Hope Medical Center
Conditions:
Adult Anaplastic Astrocytoma
Recurrent Grade III Glioma
Eligibility:
All Genders
13+ years
Phase:
PHASE1
Brief 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 treatme...
Detailed Description
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 OBJECTIV...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
August 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 11 2015
Estimated Enrollment :
15 Patients enrolled
Trial Details
Trial ID
NCT01172964
Start Date
August 1 2010
End Date
February 11 2015
Last Update
November 9 2017
Active Locations (1)
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1
City of Hope
Duarte, California, United States, 91010