Ignite Creation Date:
2025-12-24 @ 11:35 PM
Ignite Modification Date:
2026-02-21 @ 2:54 PM
Study NCT ID:
NCT05139056
Status:
RECRUITING
Last Update Posted:
2025-10-21
First Post:
2021-11-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.
Detailed Description:
PRIMARY OBJECTIVE:
I. 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. 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.
V. 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.
I. 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. 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.
V. 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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2022-10170 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 22338 | OTHER | City of Hope Medical Center | View | |
| P30CA033572 | NIH | None | https://reporter.nih.gov/quic… | View |