Adult Anaplastic AstrocytomaPhase 1NCT01172964
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
A Phase 1 study testing flucytosine, polymerase chain reaction and immunohistochemistry staining method in people with Adult Anaplastic Astrocytoma and Recurrent Grade III Glioma, run by City of Hope Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Adult Anaplastic Astrocytoma, Recurrent Grade III Glioma, Recurrent Grade IV Glioma
- What is being tested?
- flucytosine, polymerase chain reaction and immunohistochemistry staining method
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to 11 Feb 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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%
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- 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
- Patients must be tolerating oral intake
- Patients' daily total dose of dexamethasone must be < 12 mg by Day 4
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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
- Being tested
- flucytosine, polymerase chain reaction, immunohistochemistry staining method, gene therapy, pharmacological study
- Keywords
- Los Angeles
- Medical subject headings
- Astrocytoma, Oligodendroglioma, Brain Neoplasms, Glioblastoma, Gliosarcoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
flucytosineDrug
Also called 5-FC, 5-fluorocytosine, Alcobon, Ancobon
Given orally
polymerase chain reactionOther
Also called PCR
Correlative studies
immunohistochemistry staining methodOther
Also called immunohistochemistry
Correlative studies
gene therapyBiological
Also called therapy, gene
Injected at the time of the surgery to resect the tumor
Also called pharmacological studies
Correlative studies
3-Tesla magnetic resonance imagingOther
Also called 3-Tesla MRI, 3T MRI
Correlative studies
laboratory biomarker analysisOther
Correlative studies
therapeutic conventional surgeryProcedure or surgery
Surgery to resect the tumor
E. coli CD-expressing genetically modified neural stem cellsBiological
Also called HB1.F3.CD neural stem cells
Injected at the time of the surgery to resect the tumor
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the safety and feasibility of intracerebral administration of genetically-modified neural stem cells (NSCs) in combination with oral 5-fluorocytosine.
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
Measured: Day 60
Secondary outcomes (6)
Relationship between intracerebral and systemic concentrations of 5-FC and 5-FU with increasing NSC dose level
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.
Measured: Up to Day 10
Presence of 5-FU in the brain using 19F-MRS
As of 5/1/2012, study patients will no longer undergo 19F-MRS.
Measured: Day 60
Assessment of development of immunogenicity against NSCs
As of 11/30/2012 patients will no longer undergo these tests.
Measured: Day 60
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.
Measured: Day 60
Assessment of the fate of NSCs at autopsy when feasible
Measured: At autopsy
Assess the intracerebral distribution of NSCs using iron-labeling as a cellular tracker.
Measured: Up to Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2010 (estimated)
- Study startAug 2010
- Primary completion11 Feb 2015
- Study completion11 Feb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Anaplastic AstrocytomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jana Portnow, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01172964
- Sponsor's protocol ID
- 08002
- Other IDs
- NCI-2010-01388
- Status last verified
- Nov 2017
- First submitted
- 28 Jul 2010
- Last updated
- 9 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01172964
- Acronym / sponsor ID
- 08002
- Conditions
- Adult Anaplastic Astrocytoma, Recurrent Grade III Glioma, Recurrent Grade IV Glioma, Adult Anaplastic Oligodendroglioma, Adult Brain Tumor, Adult Giant Cell Glioblastoma
- Keywords
- Los Angeles
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- 11 Feb 2015 (actual)
- Study completion
- 11 Feb 2015 (actual)
- First posted
- 30 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | 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 cellsPatients 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. |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| flucytosineAlso: 5-FC, 5-fluorocytosine, Alcobon, AncobonGiven orally | Drug | Arm I |
| polymerase chain reactionAlso: PCRCorrelative studies | Other | Arm I |
| immunohistochemistry staining methodAlso: immunohistochemistryCorrelative studies | Other | Arm I |
| gene therapyAlso: therapy, geneInjected at the time of the surgery to resect the tumor | Biological | Arm I |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I |
| 3-Tesla magnetic resonance imagingAlso: 3-Tesla MRI, 3T MRICorrelative studies | Other | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
| therapeutic conventional surgerySurgery to resect the tumor | Procedure or surgery | Arm I |
| E. coli CD-expressing genetically modified neural stem cellsAlso: HB1.F3.CD neural stem cellsInjected at the time of the surgery to resect the tumor | Biological | Arm I |
Primary outcome
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
6 secondary outcomes
Relationship between intracerebral and systemic concentrations of 5-FC and 5-FU with increasing NSC dose level
Time frame: Up to Day 10
Presence of 5-FU in the brain using 19F-MRS
Time frame: Day 60
Assessment of development of immunogenicity against NSCs
Time frame: Day 60
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jana Portnow principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing flucytosine, polymerase chain reaction and immunohistochemistry staining method in people with Adult Anaplastic Astrocytoma and Recurrent Grade III Glioma, run by City of Hope Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2017.