Multiple Doses of Neural Stem Cell Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas

Recurrent Glioblastoma Clinical Trial

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

Clinical Trial Summary

This phase I trial studies the effect of multiple doses of NSC-CRAd-S-pk7 in treating patients with high-grade gliomas that have come back (recurrent). NSC-CRAd-S-pk7 consists of neural stem cells that carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.

Clinical Trial Description

PRIMARY OBJECTIVE:

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).

SECONDARY OBJECTIVES:

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.

OUTLINE:

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. ;

Related Conditions & MeSH terms

• Astrocytoma
• Glioblastoma
• Glioma
• Gliosarcoma
• Oligodendroglioma
• Recurrence
• 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

• NCT number: NCT05139056
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Recruiting
• Phase: Phase 1
• Start date: May 2, 2023
• Completion date: August 7, 2025