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

NCT05139056 | Suspended Phase 1 DMC FDA Drug

• 3 other identifiers: 22338NCI-2022-10170P30CA033572
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

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.

Conditions

Currently Only Enrolling Glioblastoma Patients at First Recurrence

Keywords

Recurrent glioblastoma, oncolytic virus, neural stem cells, first recurrence

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Assessed using the Common Terminology Criteria for Adverse Events version 5.0.

  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.

  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

  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

• Overall survival (OS)

  From time of surgery to date of death, assessed at 9 months

Study Arms (1)

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

Biological: Neural Stem Cells-expressing CRAd-S-pk7; Procedure: Resection

Interventions

Neural Stem Cells-expressing CRAd-S-pk7 BIOLOGICAL

Given intracerebrally

Also known as: CRAd-S-pk7 loaded NSCs, NSC-CRAd-S-pk7, NSC-CRAd-S-pk7 Virotherapeutic, NSCs loaded with CRAd-S-pk7, SC-CRAd-Survivin-pk7

Treatment (NSC-CRAd-S-pk7)

Resection PROCEDURE

Undergo surgical resection

Also known as: Intracerebral administration of NSC-CRAd-S-pk7 via intracavitary catheter, Removal of CSF samples via a catheter placed in the lateral cerebral ventricle

Treatment (NSC-CRAd-S-pk7)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Standford University

Stanford, California, 94305, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27109, United States

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Jana L Portnow, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 1, 2021
• Study Start: May 2, 2023
• Primary Completion (Estimated): August 7, 2026
• Study Completion (Estimated): August 7, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (4)