Repeated Neural Stem Cell Based Virotherapy for Newly Diagnosed High Grade Glioma

Glioma, Malignant Clinical Trial

Official title: A Phase I Study of Repeated Neural Stem Cell Based Virotherapy in Combination With N-Acetylcysteine Amid (NACA) and Standard Radiation and Chemotherapy for Newly Diagnosed High Grade Glioma

Status Not yet recruiting

Clinical Trial Summary

The goal of this clinical trial is to learn about the safety and feasibility of administering repeated doses of neural stem cell (NSC)-conditionally replicative adenovirus (CRAd)-survivin (S)-protomer (p)k7, in persons with newly diagnosed high grade glioma.

The main questions it aims to answer are:

• whether multiple doses of NSC-CRAd-S-pk7 are safe and feasible

• how multiple doses of NSC-CRAd-S-pk7 influence tumor response, overall survival, time to tumor progression, and quality of life.

Participants will:

• undergo a biopsy to confirm high grade glioma, then receive the first dose of NSC-CRAd-S-pk7 into the brain

• about 2 weeks later, undergo surgery to remove the tumor and receive the second dose of NSC-CRAd-S-pk7 into the brain

• start chemoradiation about 2 weeks after surgery, then about 2 weeks later, receive the 3rd dose of NSC-CRAd-S-pk7 into the brain

• four weeks later, at the end of chemoradiation, receive a fourth dose of NSC-CRAd-S-pk7 into the brain.

• after radiation is finished, receive standard of care chemotherapy and tumor-treating fields. Two additional doses of NSC-CRAd-S-pk7 will be given every 4 weeks.

Every other patient enrolled will receive N-acetylcysteine amide (NACA), from registration until the day prior to surgery and the second dose of NSC-CRAd-S-pk7.

Clinical Trial Description

The treatment regimen contains 3 phases:

Surgical phase:

Patients undergo a biopsy and upon intraoperative confirmation of high grade glioma, NSC-CRAd-S-pk7 dose #1 will be injected into the biopsy site. Patients will undergo resection of the tumor 14 (+/- 3) days later, administration of second dose of the investigational product (NSC-CRAd-S-pk7 dose #2), and implantation of the catheter system. The investigational product will then be given monthly for a total of 6 doses (see below).

Every other patient enrolled (beginning with the first patient) will also undergo oral administration of NACA (an over-the-counter drug that acts as a free radical scavenger and improves NSC viability) starting at registration until the day prior to surgical tumor resection and planned investigational product injection #2.

Radiotherapy phase:

After recovery from surgery (usually within 2 weeks), standard chemoradiotherapy will be initiated consisting of daily radiotherapy (2 Gy per fraction x 30 fractions) and concomitant temozolomide (TMZ) chemotherapy (75 mg/m2 daily from day 1 of RT until last day of RT).

About 10-14 days into radiotherapy (= approx. 4 weeks after intraoperative dose #2), patients will be receiving NSC-CRAd-S-pk7 dose #3 through the previously implanted catheter system. This also marks the beginning of the formal dose-limiting toxicity (DLT) period, as this virus' survivin gene promoter is activated by the concomitant irradiation.

Four weeks later, ie. at the end of radiotherapy dose #4 is administered as previously, provided no DLT toxicity has been observed and viral treatment related toxicities have returned to grade ≤ 2.

Adjuvant (also called maintenance) phase:

As per standard of care, approx. 4 weeks after end of radiotherapy, patients will start maintenance TMZ chemotherapy (150 - 200 mg/m2, daily x 5 every 28 days) and loco-regional treatment with alternating Tumor Treating Fields (TTFields, Optune®). NSC-CRAd-S-pk7 doses #5 and #6 will be administered concurrently (± 3 days) with adjuvant cycle 1 and 2 of TMZ. ;

Related Conditions & MeSH terms

• Glioma
• Glioma, Malignant
• New Diagnosis Tumor

• NCT number: NCT06169280
• Study type: Interventional
• Source: Northwestern University
• Contact: Christina Amidei, PhD
• Phone: (312) 695-9124
• Email: christina.amidei@nm.org
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 1, 2024
• Completion date: December 31, 2030