Currently Only Enrolling Glioblastoma Patients at First RecurrencePhase 1NCT05139056
Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas
A Phase 1 study testing Neural Stem Cells-expressing CRAd-S-pk7 and Resection in people with Currently Only Enrolling Glioblastoma Patients at First Recurrence, run by City of Hope Medical Center at 4 sites in United States.
Trial summary
This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence. NSC-CRAd-S-pk7 consists of neural stem cells that can target glioblastoma cells and carry a virus, which can kill cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Currently Only Enrolling Glioblastoma Patients at First Recurrence
- What is being tested?
- Neural Stem Cells-expressing CRAd-S-pk7 and Resection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 4 sitesUnited States
- Study dates
- 2 May 2023to 7 Feb 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be age >= 18 years
- Patient has a Karnofsky performance status of >= 70%
- Patient has a life expectancy of >= 3 months
- When determining the maximum tolerated number of treatment cycles (MTC): patient has a histologically confirmed diagnosis of a grade 3 or 4 glioma (eg., glioblastoma, grade 4 astrocytoma, grade 3 astrocytoma, grade 3 oligodendroglioma). (This part of the study has been completed).
- When enrolling to Treatment Schedules 4 and 4a: patient has glioblastoma at first recurrence.
- Imaging studies show evidence of recurrent, supratentorial tumor(s).
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- Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
- The patient must be in need of surgery for tumor resection
- Based on the neurosurgeon's judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
- Absolute neutrophil count (ANC) of >= 1000 cells/mm^3
- 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
- At least 2 weeks from taking the last dose of a targeted agent
- At least 4 weeks from the last dose of bevacizumab For temozolomide, an interval of 23 days is required from the last dose administered if the patient was recently treated with adjuvant temozolomide, consisting of temozolomide daily for 5 days, repeated every 28 days.
- At least 2 weeks from taking the last dose of a targeted agent.
- At least 4 weeks from the last dose of bevacizumab.
- All significant toxicities from previous anticancer therapy must have stabilized to a new baseline or resolved.
- All participants must have the ability to understand and the willingness to sign a written informed consent.
- The effects of this treatment on a developing fetus are unknown. Therefore, female patients of childbearing potential and sexually-active male patients or who are able to impregnate their partner, must agree to use an effective method of contraception while participating in this study. Patients of childbearing potential must have a negative pregnancy test =< 2 week prior to registration.
Who cannot join
- Patient has multi-focal disease.
- Patient is receiving radiation, chemotherapy, or another investigational agent.
- Patient has had prior therapy with neural stem cells.
- Patient has not recovered from any toxicity (> grade 1) of prior therapies, except alopecia.
- Patient is unable to undergo a brain MRI.
- Patient has chronic or active viral infections of the central nervous system (CNS).
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- Patient has a coagulopathy or bleeding disorder.
- Patient has an uncontrolled illness including ongoing or active infection.
- Patient has another active malignancy.
- Patient is pregnant or breastfeeding.
- A patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 3 recruiting
- Suspended
Northwestern University
Chicago, Illinois, 60611
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Jana L. Portnow, 626-218-9393, braintumortrials@coh.org
Jana L. Portnow, MD
- Recruiting
Standford University
Stanford, California, 94305
Melanie H Hayden Gephart, MD, 650-497-7777, braintumorcenter@stanfordhealthcare.org
- Not yet recruiting
Wake Forest University
Winston-Salem, North Carolina, 27109
Glenn Lesser, MD, 336-716-9527, glesser@wakehealth.edu
About this study
Official title: A Phase I Study of Multiple Doses of Neural Stem Cell-Based Oncolytic Virotherapy (NSC-CRAd-S-pk7) Administered Intracerebrally to Patients With Recurrent High-Grade Gliomas
This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence. NSC-CRAd-S-pk7 consists of neural stem cells that can target glioblastoma cells and carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the recommended maximum tolerated number of cycles (MTC) of intracavitary (ICT) administered neural stem cell-expressing CRAd-S-pk7 (NSCCRAd-S-pk7) for phase II testing based on dose-limiting toxicities (DLTs), the overall toxicity profile, and activity in patients with recurrent high-grade glioma (HGG).
II. Describe and compare the weekly dosing schedule (Treatment Schedule 4) to an every 2 week dosing schedule (Treatment Schedule 4a) of intracerebrally administered NSC-CRAd-S-pk7 based on DLTs, the overall toxicity profile, and activity in patients with glioblastoma at first recurrence.
III. Determine the recommended phase 2 dose schedule based on the overall toxicity profile, and activity in patients with recurrent high grade gliomas
SECONDARY OBJECTIVES:
- I. Assess for evidence of biologic activity (cytotoxicity and anti-tumor immune responses) in posttreatment tissue samples.
II. Assess for the presence of NSC and/or CRAd-S-pk7 in post-treatment tissue samples.
III. Assess for possible development of antibody and T cell responses to the NSCs and/or CRAd-S-pk7 in CSF and blood.
IV. Assess for evidence of possible migration of NSCs and/or CRAd-S-pk7 outside of the brain and if so, determine if viral shedding is occurring.
- Determine the persistence and intracerebral distribution of the NSCs and/or CRAd-S-pk7 whenever permission is given to perform a brain autopsy on a study participant.
VI. Estimate the rates of disease response, progression-free survival at 6 months (PFS6mo) and overall survival at 9 months (OS9mo) for all study participants and separately for the cohorts of glioblastoma patients at first recurrence treated at the MTC administered once a week or every 2 weeks.
VII. Identify a molecular signature of vulnerability for predicting which glioma patients will benefit most from treatment with NSC-CRAd-S-pk7.
VIII. Describe and compare changes in immunosuppressive and immunostimulatory cytokines in CSF from study participants enrolled to Treatment Schedules 4 and 4a.
IX. Assess for the presence of exhausted T cell phenotypes in CSF samples and compare the degree of T cell exhaustion in study participants enrolled to Treatment Schedules 4 and 4a.
OUTLINE:
Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks via a catheter placed during surgery. A second catheter is placed in the cerebral ventricle to obtain serial samples of CSF for correlative studies. Two weeks after the last dose of study agent is administered, study participants undergo a second surgical procedure to remove the catheters and obtain post-treatment tissue samples for analysis.
FINANCIAL ASSISTANCE:
There is funding to help with the cost of transportation, lodging, and meals for participants who qualify for financial assistance.
- Being tested
- Neural Stem Cells-expressing CRAd-S-pk7, Resection
- Keywords
- Recurrent glioblastoma, oncolytic virus, neural stem cells, first recurrence
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neural Stem Cells-expressing CRAd-S-pk7Biological
Also called CRAd-S-pk7 loaded NSCs, NSC-CRAd-S-pk7, NSC-CRAd-S-pk7 Virotherapeutic, NSCs loaded with CRAd-S-pk7
Given intracerebrally
ResectionProcedure or surgery
Also called Intracerebral administration of NSC-CRAd-S-pk7 via intracavitary catheter, Removal of CSF samples via a catheter placed in the lateral cerebral ventricle
Undergo surgical resection
| Study group | Role | What they receive |
|---|---|---|
| Treatment (NSC-CRAd-S-pk7) | Experimental | Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks (depending on when they enroll in the study) via a catheter that was placed during surgery Receives: Biological: Neural Stem Cells-expressing CRAd-S-pk7; Procedure: Resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Assessed using the Common Terminology Criteria for Adverse Events version 5.0.
Measured: Up to 30 days post removal of Rickhams
Progression-free survival (PFS)
Will estimate the rate 90% confidence interval (CI) for PFS at 6 months and use Kaplan Meier methods to estimate median PFS for all study participants as well as for the cohorts of glioblastoma (GBM) participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 given once a week or every two weeks.
Measured: From the time of surgery to the event date of progression, assessed at 6 months]
Secondary outcomes (9)
Neural Stem Cells-expressing CRAd-S-pk7 (NSC-CRAd-S-pk7) immunogenicity
Measured: Up to 30 days post removal of Rickhams
NSC-CRAd-S-pk7 migration within the brain
Neural stem-cells and/or free viral particles will be assessed in samples of post-treatment tissue samples.
Measured: Up to 30 days post removal of Rickhams
NSC-CRAd-S-pk7 migration outside the brain
- Neural stem-cells and/or free viral particles will be assessed in samples of CSF, peripheral blood, urine, oral and rectal mucosa (via swabbing), and skin at the injection site (also via swabbing).
Measured: Up to 30 days post removal of Rickhams
Disease response
Response Assessment in Neuro-Oncology Criteria will be used to assess response on brain magnetic resonance imaging in all study participants who receive at least 80% of the planned doses of study treatment. Disease response will be similarly assessed for the cohorts of GBM participants at first recurrence who will be treated with 4 doses of NSC-CRAD-S-pk7 once a week or every two weeks.
Measured: Up to 2 years
Overall survival (OS)
Will estimate the rate 90% CI for OS at 9 months and use Kaplan Meier methods to estimate median OS for all study participants as well as for the cohorts of GBM participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 once a week or every two weeks.
Measured: From time of surgery to date of death, assessed at 9 months
Changes in HSPG and survivin expression
Changes in survivin expression by immunohistochemistry IHC in pre- and post-treatment tissue to see if there is a relationship with disease response.
Measured: Baseline up to 2 years
Changes in immune cell populations
Changes in immune cell populations in the tumor microenvironment in pre- and post-treatment tumor tissue samples will be assessed by Vectra Spectral Imaging.
Measured: Baseline up to 2 years
Changes in tumor growth
Develop a biomathematical model for predicting tumor response to study treatment.
Measured: Baseline up to 2 years
Assessed using multiplex immunoassays in cerebrospinal fluid (CSF) samples and RNA-sequencing in CSF, peripheral blood, and tumor tissue samples.
Measured: Up to 30 days post removal of Rickhams
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start2 May 2023
- Primary completion7 Feb 2028 (estimated)
- Study completion7 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Currently Only Enrolling Glioblastoma Patients at First RecurrenceStudies 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
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jana L Portnow, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05139056
- Sponsor's protocol ID
- 22338
- Other IDs
- NCI-2022-10170, 22338, P30CA033572
- Status last verified
- Nov 2026
- First submitted
- 22 Nov 2021
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Multiple Doses of Neural Stem Cell-Based Oncolytic Virotherapy (NSC-CRAd-S-pk7) Administered Intracerebrally to Patients With Recurrent High-Grade Gliomas
- ClinicalTrials.gov ID
- NCT05139056
- Acronym / sponsor ID
- 22338
- Keywords
- Recurrent glioblastoma, oncolytic virus, neural stem cells, first recurrence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 2 May 2023 (actual)
- Primary completion
- 7 Feb 2028 (estimated)
- Study completion
- 7 Feb 2028 (estimated)
- First posted
- 1 Dec 2021 (actual)
- 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.
This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence. NSC-CRAd-S-pk7 consists of neural stem cells that can target glioblastoma cells and carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVE:
- Determine the recommended maximum tolerated number of cycles (MTC) of intracavitary (ICT) administered neural stem cell-expressing CRAd-S-pk7 (NSCCRAd-S-pk7) for phase II testing based on dose-limiting toxicities (DLTs), the overall toxicity profile, and activity in patients with recurrent high-grade glioma (HGG).
II. Describe and compare the weekly dosing schedule (Treatment Schedule 4) to an every 2 week dosing schedule (Treatment Schedule 4a) of intracerebrally administered NSC-CRAd-S-pk7 based on DLTs, the overall toxicity profile, and activity in patients with glioblastoma at first recurrence.
III. Determine the recommended phase 2 dose schedule based on the overall toxicity profile, and activity in patients with recurrent high grade gliomas
SECONDARY OBJECTIVES:
- I. Assess for evidence of biologic activity (cytotoxicity and anti-tumor immune responses) in posttreatment tissue samples.
II. Assess for the presence of NSC and/or CRAd-S-pk7 in post-treatment tissue samples.
III. Assess for possible development of antibody and T cell responses to the NSCs and/or CRAd-S-pk7 in CSF and blood.
IV. Assess for evidence of possible migration of NSCs and/or CRAd-S-pk7 outside of the brain and if so, determine if viral shedding is occurring.
- Determine the persistence and intracerebral distribution of the NSCs and/or CRAd-S-pk7 whenever permission is given to perform a brain autopsy on a study participant.
VI. Estimate the rates of disease response, progression-free survival at 6 months (PFS6mo) and overall survival at 9 months (OS9mo) for all study participants and separately for the cohorts of glioblastoma patients at first recurrence treated at the MTC administered once a week or every 2 weeks.
VII. Identify a molecular signature of vulnerability for predicting which glioma patients will benefit most from treatment with NSC-CRAd-S-pk7.
VIII. Describe and compare changes in immunosuppressive and immunostimulatory cytokines in CSF from study participants enrolled to Treatment Schedules 4 and 4a.
IX. Assess for the presence of exhausted T cell phenotypes in CSF samples and compare the degree of T cell exhaustion in study participants enrolled to Treatment Schedules 4 and 4a.
OUTLINE:
Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks via a catheter placed during surgery. A second catheter is placed in the cerebral ventricle to obtain serial samples of CSF for correlative studies. Two weeks after the last dose of study agent is administered, study participants undergo a second surgical procedure to remove the catheters and obtain post-treatment tissue samples for analysis.
FINANCIAL ASSISTANCE:
There is funding to help with the cost of transportation, lodging, and meals for participants who qualify for financial assistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (NSC-CRAd-S-pk7) | Experimental | Biological: Neural Stem Cells-expressing CRAd-S-pk7, Procedure: ResectionPatients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks (depending on when they enroll in the study) via a catheter that was placed during surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patient must be age >= 18 years
- Patient has a Karnofsky performance status of >= 70%
- Patient has a life expectancy of >= 3 months
- Imaging studies show evidence of recurrent, supratentorial tumor(s).
- Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
Key exclusion criteria (11 listed)
- Patient has multi-focal disease.
- Patient is receiving radiation, chemotherapy, or another investigational agent.
- Patient has had prior therapy with neural stem cells.
- Patient has not recovered from any toxicity (> grade 1) of prior therapies, except alopecia.
- Patient is unable to undergo a brain MRI.
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 |
|---|---|---|
| Neural Stem Cells-expressing CRAd-S-pk7Also: CRAd-S-pk7 loaded NSCs, NSC-CRAd-S-pk7, NSC-CRAd-S-pk7 Virotherapeutic, NSCs loaded with CRAd-S-pk7Given intracerebrally | Biological | Treatment (NSC-CRAd-S-pk7) |
| ResectionAlso: Intracerebral administration of NSC-CRAd-S-pk7 via intracavitary catheter, Removal of CSF samples via a catheter placed in the lateral cerebral ventricleUndergo surgical resection | Procedure or surgery | Treatment (NSC-CRAd-S-pk7) |
Primary outcome
Incidence of adverse events
Time frame: Up to 30 days post removal of Rickhams
Assessed using the Common Terminology Criteria for Adverse Events version 5.0.
Progression-free survival (PFS)
Time frame: From the time of surgery to the event date of progression, assessed at 6 months]
Will estimate the rate 90% confidence interval (CI) for PFS at 6 months and use Kaplan Meier methods to estimate median PFS for all study participants as well as for the cohorts of glioblastoma (GBM) participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 given once a week or every two weeks.
9 secondary outcomes
Neural Stem Cells-expressing CRAd-S-pk7 (NSC-CRAd-S-pk7) immunogenicity
Time frame: Up to 30 days post removal of Rickhams
NSC-CRAd-S-pk7 migration within the brain
Time frame: Up to 30 days post removal of Rickhams
NSC-CRAd-S-pk7 migration outside the brain
Time frame: Up to 30 days post removal of Rickhams
Disease response
Time frame: Up to 2 years
Overall survival (OS)
Time frame: From time of surgery to date of death, assessed at 9 months
Changes in HSPG and survivin expression
Time frame: Baseline up to 2 years
Changes in immune cell populations
Time frame: Baseline up to 2 years
Changes in tumor growth
Time frame: Baseline up to 2 years
Assessed using multiplex immunoassays in cerebrospinal fluid (CSF) samples and RNA-sequencing in CSF, peripheral blood, and tumor tissue samples.
Time frame: Up to 30 days post removal of Rickhams
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
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.
Jana L Portnow, MD principal investigator
City of Hope Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Neural Stem Cells-expressing CRAd-S-pk7 and Resection in people with Currently Only Enrolling Glioblastoma Patients at First Recurrence, run by City of Hope Medical Center at 4 sites 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 21 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 30 days post removal of Rickhams). The study lists 2 primary outcomes in all. 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 4 Nov 2026.