NCT01172964

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 13 Years
• Healthy volunteers: Not accepted

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.

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assess the presence of 5-FU in the brain with the use of fluorine (19F)-magnetic resonance spectroscopy (MRS)(no longer in effect as of 5/1/2012).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

Conditions

• 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

Interventions

Type	Name	Description
DRUG	flucytosine	Given orally
OTHER	polymerase chain reaction	Correlative studies
OTHER	immunohistochemistry staining method	Correlative studies
BIOLOGICAL	gene therapy	Injected at the time of the surgery to resect the tumor
OTHER	pharmacological study	Correlative studies
OTHER	3-Tesla magnetic resonance imaging	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies
PROCEDURE	therapeutic conventional surgery	Surgery to resect the tumor
BIOLOGICAL	E. coli CD-expressing genetically modified neural stem cells	Injected at the time of the surgery to resect the tumor

Timeline

• Start date: 2010-08-01
• Primary completion: 2015-02-11
• Completion: 2015-02-11
• First posted: 2010-07-30
• Last updated: 2017-11-09

Locations

1 site across 1 country: United States