Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Glioma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

Gliosarcoma

Disease Attributes

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Tumor, Adult

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Oligoastrocytoma

Anaplastic Oligoastrocytoma

Neuroepithelioma

Anti-Infective Agents

All Drugs and Chemicals

Flucytosine

Clotrimazole

Miconazole

Antifungal Agents

Antimetabolites

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.

flucytosine

polymerase chain reaction

immunohistochemistry staining method

Injected at the time of the surgery to resect the tumor

gene therapy

pharmacological study

3-Tesla magnetic resonance imaging

laboratory biomarker analysis

therapeutic conventional surgery

E. coli CD-expressing genetically modified neural stem cells

Jana Portnow

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.

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assess the presence of 5-FU in the brain with the use of fluorine (19F)-magnetic resonance spectroscopy (MRS)(no longer in effect as of 5/1/2012).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.

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

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

Summarized by NSC dose cohort using descriptive statistics and graphs. The Macdonald Criteria will be used to assess response. As of 11/30/2012 patients will no longer undergo these tests.

As of 5/1/2012, study patients will no longer undergo 19F-MRS.

As of 11/30/2012 patients will no longer undergo these tests.

City of Hope Medical Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT01172964	Adult Anaplasti... Recurrent Grade... Recurrent Grade... Adult Anaplasti... Adult Brain Tum... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Adult Mixed Gli... Recurrent Adult... Adult Anaplasti... Recurrent High ...	flucytosine polymerase chai... immunohistochem... gene therapy pharmacological... 3-Tesla magneti... laboratory biom... therapeutic con... E. coli CD-expr...	13 Years -	City of Hope Medical Center
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	NCT01172964	Adult Anaplasti... Recurrent Grade... Recurrent Grade... Adult Anaplasti... Adult Brain Tum... Adult Giant Cel... Adult Glioblast... Adult Gliosarco... Adult Mixed Gli... Recurrent Adult... Adult Anaplasti... Recurrent High ...	flucytosine polymerase chai... immunohistochem... gene therapy pharmacological... 3-Tesla magneti... laboratory biom... therapeutic con... E. coli CD-expr...	13 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for recurrent grade iv glioma