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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05139056

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

14.2

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
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	Phase 1

Detailed Description

PRIMARY OBJECTIVE:

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:

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.
Evaluate the intracerebral biodistribution of NSC-CRAd-S-pk7 when permission to perform a brain autopsy on a study participant is given.
Identify the evidence of possible NSC migration outside of the brain, the presence of viral particles, and/or both in the CSF and blood.
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.
Assess changes in HSPG and survivin expression in pre- and post-treatment tumor tissue samples treatment.
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.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 15, 2022

Anticipated Primary Completion Date :

Dec 20, 2023

Anticipated Study Completion Date :

Dec 20, 2023

Arms and Interventions

Arm	Intervention/Treatment
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 Given intracerebrally Other Names: CRAd-S-pk7 loaded NSCs NSC-CRAd-S-pk7 NSC-CRAd-S-pk7 Virotherapeutic NSCs loaded with CRAd-S-pk7 SC-CRAd-Survivin-pk7 Procedure: Resection Undergo surgical resection Other Names: Surgical Resection

Arm

Intervention/Treatment

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

Given intracerebrally

Other Names:

CRAd-S-pk7 loaded NSCs

NSC-CRAd-S-pk7

NSC-CRAd-S-pk7 Virotherapeutic

NSCs loaded with CRAd-S-pk7

SC-CRAd-Survivin-pk7

Procedure: Resection

Undergo surgical resection

Other Names:

Surgical Resection

Outcome Measures

Primary Outcome Measures

Incidence of adverse events [Up to 30 days post removal of Rickhams]
Assessed using the Common Terminology Criteria for Adverse Events version 5.0.

Secondary Outcome Measures

Neural Stem Cells-expressing CRAd-S-pk7 (NSC-CRAd-S-pk7) immunogenicity [Up to 30 days post removal of Rickhams]
NSC-CRAd-S-pk7 migration within the brain [Up to 30 days post removal of Rickhams]
NSC-CRAd-S-pk7 migration outside the brain [Up to 30 days post removal of Rickhams]
Disease response [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) [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) [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 [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 [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 [Baseline up to 2 years]
Develop a biomathematical model for predicting tumor response to study treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must be age >= 18 years
Patient has a Karnofsky performance status of >= 70%
Patient has a life expectancy of >= 3 months
Patient has histologically-confirmed, diagnosis of a grade III or IV glioma (including glioblastoma, anaplastic astrocytoma, gliosarcoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, not otherwise specified [NOS]), 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 presence of infratentorial tumor is allowed if the patient also has supratentorial disease that is amenable to placement of an intracavitary Rickham catheter
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 6 weeks must have elapsed since taking a nitrosourea-containing chemotherapy regimen
At least 4 weeks since completing a non-nitrosourea-containing cytotoxic chemotherapy regimen (except temozolomide: only an interval of 23 days is required from the last dose administered when patient has been recently treated with the standard temozolomide regimen of 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
There is no limit to the number of prior therapies for enrollment during treatment schedule escalation; however, once the maximum tolerated treatment schedule has been identified further enrollment to complete the accrual goal of 12 participants treated at the maximum tolerated treatment schedule will be limited to glioblastoma patients at first or second recurrence
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 must agree to use an effective method of contraception while participating in this study. Women of childbearing potential must have a negative pregnancy test =< 2 week prior to registration

Exclusion Criteria:

Patient has anti-human leukocyte antigen (HLA) antibodies specific for HLA Class I antigens (A01, A31, B07, B15, C*07) expressed by the neural stem cells
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)
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