Clinical trial · Interventional
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
NCT01172964CI-TRIAL-00030259completedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (12)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Adult Anaplastic Astrocytoma | Adult Anaplastic Astrocytoma | ONTOLOGY_EXACT | 0.98 |
| Adult Anaplastic Oligoastrocytoma | Anaplastic Oligoastrocytoma | CURATED_BROADER | 0.80 |
| Adult Anaplastic Oligodendroglioma | Adult Anaplastic Oligodendroglioma | ONTOLOGY_EXACT | 0.98 |
| Adult Brain Tumor | Adult Brain Neoplasm | ALIAS | 0.90 |
| Adult Giant Cell Glioblastoma | Adult Giant Cell Glioblastoma | ONTOLOGY_EXACT | 0.98 |
| Adult Glioblastoma | Adult Glioblastoma | ONTOLOGY_EXACT | 0.98 |
| Adult Gliosarcoma | Adult Gliosarcoma | ONTOLOGY_EXACT | 0.98 |
| Adult Mixed Glioma | Adult Mixed Glioma | ONTOLOGY_EXACT | 0.98 |
| Recurrent Adult Brain Tumor | Adult Brain Neoplasm |
Interventions
Interventions (9)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 3-Tesla magnetic resonance imaging | Other | — | UNRESOLVED |
| E. coli CD-expressing genetically modified neural stem cells | Biological | — | UNRESOLVED |
| flucytosine | Drug | — | UNRESOLVED |
| gene therapy | Biological | — | UNRESOLVED |
| immunohistochemistry staining method | Other | — | UNRESOLVED |
| laboratory biomarker analysis | Other | — | UNRESOLVED |
| pharmacological study | Other | — | UNRESOLVED |
| polymerase chain reaction | Other | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Arm I
- description
- 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.
- interventionNames
- Drug: flucytosine
- Other: polymerase chain reaction
- Other: immunohistochemistry staining method
- Biological: gene therapy
- Other: pharmacological study
- Other: 3-Tesla magnetic resonance imaging
- Other: laboratory biomarker analysis
- Procedure: therapeutic conventional surgery
- Biological: E. coli CD-expressing genetically modified neural stem cells
Primary outcomes (1)
- measure
- Determination of the safety and feasibility of intracerebral administration of genetically-modified neural stem cells (NSCs) in combination with oral 5-fluorocytosine.
- timeFrame
- Day 60
- description
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 13 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available
No reference posted for this study.