Multiple Doses of Neural Stem Cell Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas
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|ClinicalTrials.gov Identifier: NCT05139056
Recruitment Status : Recruiting
First Posted : December 1, 2021
Last Update Posted : June 27, 2023
|Condition or disease
|Recurrent Anaplastic Astrocytoma Recurrent Anaplastic Oligoastrocytoma Recurrent Anaplastic Oligodendroglioma Recurrent Glioblastoma Recurrent Gliosarcoma Recurrent Malignant Glioma Recurrent WHO Grade II Glioma Recurrent WHO Grade III Glioma
|Biological: Neural Stem Cells-expressing CRAd-S-pk7 Procedure: Resection
I. Determine the recommended maximum tolerated number of cycles (MTC) of intracavitary (ICT) administered Neural Stem Cells-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).
I. Measure possible development of antibody and T cell responses to the neural stem cells (NSCs) and/or the oncolytic virus in cerebrospinal fluid (CSF), resection cavity fluid (when possible to obtain by aspiration before administering study agent through the ICT Rickham), and blood.
II. Evaluate the intracerebral biodistribution of NSC-CRAd-S-pk7 when permission to perform a brain autopsy on a study participant is given.
III. Identify the evidence of possible NSC migration outside of the brain, the presence of viral particles, and/or both in the CSF and blood.
IV. Estimate the rates of disease response using modified Response Assessment in Neuro-Oncology (RANO) criteria, progression-free survival at 6 months (PFS6months), overall survival at 9 months (OS9months), and median PFS and OS in the recurrent HGG patients, and estimate the rates of disease response, PFS6months, and OS9months for the cohort of 12 GBM patients at first or second recurrence who will be treated at the MTC.
V. Assess changes in HSPG and survivin expression in pre- and post-treatment tumor tissue samples treatment.
VI. Identify possible mechanisms of immune escape by analyzing immune cell population changes in the tumor microenvironment (TME) in pre- and post-treatment tumor tissue samples.
VII. Generate a biomathematical model to describe spatial temporal changes in tumor growth that may predict the effect of NSC-CRAd-S-pk7 on tumor response based on magnetic resonance imaging (MRI) measurements.
Patients undergo standard of care surgical resection. Patients then receive NSC-CRAd-S-pk7 intracerebrally over 10 minutes once weekly (QW) for up to 4 doses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3 and 6 months, and then annually thereafter.
|Study Type :
|Interventional (Clinical Trial)
|Estimated Enrollment :
|Single Group Assignment
|None (Open Label)
|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
|Actual Study Start Date :
|May 2, 2023
|Estimated Primary Completion Date :
|December 20, 2023
|Estimated Study Completion Date :
|December 20, 2023
Experimental: Treatment (NSC-CRAd-S-pk7)
Patients undergo standard of care surgical resection. Patients then receive NSC-CRAd-S-pk7 intracerebrally over 10 minutes QW for up to 4 doses in the absence of disease progression or unacceptable toxicity.
Biological: Neural Stem Cells-expressing CRAd-S-pk7
Undergo surgical resection
Other Name: Surgical Resection
- 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.
- 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 ]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 cohort of 12 glioblastoma (GBM) participants at first or second recurrence who will be treated at the maximum tolerated number of cycles (MTC).
- 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 cohort of 12 GBM participants at first or second recurrence who will be treated at the MTC.
- Overall survival (OS) [ Time Frame: From time of surgery to date of death, assessed at 9 months ]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 cohort of 12 GBM participants at first or second recurrence who will be treated at the MTC.
- Changes in HSPG and survivin expression [ Time Frame: Baseline up to 2 years ]Changes in HSPG and survivin expression by immunohistochemistry IHC in pre- and post-treatment tissue to see if there is a relationship with disease response.
- Changes in immune cell populations [ Time Frame: Baseline up to 2 years ]Changes in immune cell populations in the tumor microenvironment in pre- and posttreatment tumor tissue samples will be assessed by Vectra Spectral Imaging.
- Changes in tumor growth [ Time Frame: Baseline up to 2 years ]Develop a biomathematical model for predicting tumor response to study treatment.
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): NCT05139056
|United States, California
|City of Hope Medical Center
|Duarte, California, United States, 91010
|Contact: Jana L. Portnow 626-218-3793 firstname.lastname@example.org
|Principal Investigator: Jana L. Portnow
|Jana L Portnow
|City of Hope Medical Center