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
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|ClinicalTrials.gov Identifier: NCT01172964|
Recruitment Status : Completed
First Posted : July 30, 2010
Last Update Posted : November 9, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|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||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||Phase 1|
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assess the presence of 5-FU in the brain with the use of fluorine (19F)-magnetic resonance spectroscopy (MRS)(no longer in effect as of 5/1/2012).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 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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||February 11, 2015|
|Actual Study Completion Date :||February 11, 2015|
Experimental: Arm I
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.
Other: polymerase chain reaction
Other Name: PCR
Other: immunohistochemistry staining method
Other Name: immunohistochemistry
Biological: gene therapy
Injected at the time of the surgery to resect the tumor
Other Name: therapy, gene
Other: pharmacological study
Other Name: pharmacological studies
Other: 3-Tesla magnetic resonance imaging
Other: laboratory biomarker analysis
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
Other Name: HB1.F3.CD neural stem cells
- Determination of the safety and feasibility of intracerebral administration of genetically-modified neural stem cells (NSCs) in combination with oral 5-fluorocytosine. [ Time Frame: Day 60 ]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
- Relationship between intracerebral and systemic concentrations of 5-FC and 5-FU with increasing NSC dose level [ Time Frame: Up to Day 10 ]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.
- Presence of 5-FU in the brain using 19F-MRS [ Time Frame: Day 60 ]As of 5/1/2012, study patients will no longer undergo 19F-MRS.
- Assessment of development of immunogenicity against NSCs [ Time Frame: Day 60 ]As of 11/30/2012 patients will no longer undergo these tests.
- Obtain 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. [ Time Frame: Day 60 ]
- Assessment of the fate of NSCs at autopsy when feasible [ Time Frame: At autopsy ]
- Assess the intracerebral distribution of NSCs using iron-labeling as a cellular tracker. [ Time Frame: Up to Day 10 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01172964
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|Principal Investigator:||Jana Portnow||City of Hope Medical Center|