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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

13 Years
Open (Enrolling)
Adult Anaplastic Astrocytoma, Recurrent Grade III Glioma, Recurrent Grade IV Glioma, Adult Anaplastic Oligodendroglioma, Adult Brain Tumor, Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Adult Mixed Glioma, Recurrent Adult Brain Tumor, Adult Anaplastic Oligoastrocytoma, Recurrent High Grade Glioma

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Trial Information

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


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.


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(19F)-magnetic resonance spectroscopy (MRS)(no longer in effect as of 5/1/2012).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

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.


This is a dose-escalation study.

At the time of 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.

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 +/-

- 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

- 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

- 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


- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determination of the safety and feasibility of intracerebral administration of genetically-modified neural stem cells (NSCs) in combination with oral 5-fluorocytosine.

Outcome Description:

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

Outcome Time Frame:

Day 60

Safety Issue:


Principal Investigator

Jana Portnow

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

Related Keywords:

  • Adult Anaplastic Astrocytoma
  • Recurrent Grade III Glioma
  • Recurrent Grade IV Glioma
  • Adult Anaplastic Oligodendroglioma
  • Adult Brain Tumor
  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Adult Mixed Glioma
  • Recurrent Adult Brain Tumor
  • Adult Anaplastic Oligoastrocytoma
  • Recurrent High Grade Glioma
  • Los Angeles
  • Astrocytoma
  • Brain Neoplasms
  • Glioblastoma
  • Glioma
  • Oligodendroglioma
  • Gliosarcoma



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