Clinical Trials Logo

Clinical Trial Summary

This study is a clinical trial to assess the efficacy and confirm the safety of intratumoral inoculation of G207 (an experimental virus therapy) combined with a single 5 Gy dose of radiation in recurrent/progressive pediatric high-grade gliomas


Clinical Trial Description

Outcomes for children with recurrent or progressive high-grade glioma (brain tumor) are very poor, and there are a lack of effective salvage therapies once a patient fails standard treatments. Novel innovative treatments are greatly needed. G207 is an oncolytic herpes simplex virus-1 (HSV) that has been successfully engineered to introduce mutations in the virus that enable it to selectively replicate in and kill cancer cells, but not normal cells. Replication of G207 in the tumor not only kills the infected tumor cells, but causes the tumor cell to act as a factory to produce new virus. These virus particles are released as the tumor cell dies, and can then proceed to infect other tumor cells in the vicinity, and continue the process of tumor kill. In addition to this direct oncolytic activity, the virus engenders an anti-tumor immune response; the virus is immunogenic and produces a debris field which exposes cancer cell antigens to immune cells, which can target other cancer cells. Thus, the oncolytic effect of the virus and the immune response that the virus stimulates provide a dual attack against cancer cells. In preclinical studies, a single 5 Gy dose of radiation within 24 hours of virus inoculation to the tumor increased virus replication and tumor cell killing. Radiation may also enhance the immune response against the tumor. The University of Alabama at Birmingham has conducted three phase I trials of G207 injected into the recurrent tumor alone or combined with a single dose of radiation in adults with recurrent high-grade gliomas. In these trials, high doses (up to 3 x 10^9 plaque-forming units) of virus were safely injected directly into the tumor or surrounding brain tissue without serious toxicities. Radiographic and neuropathologic evidence of an antitumor response was seen in some patients. Preclinical laboratory studies have demonstrated that a variety of aggressive pediatric brain tumor types are sensitive to G207. A Phase I study of intratumoral G207 alone or combined with a 5 Gy dose of radiation in children ages 3-18 with biopsy-confirmed recurrent/progressive supratentorial brain tumors recently completed the highest planned dose level (UAB1472; NCT02457845). The study used a 3 + 3 design with 4 dose cohorts.12 Patients underwent stereotactic placement of up to 4 intratumoral catheters. The following day they received a single controlled-rate infusion of G207 (1 x 10^7 or 1 x 10^8 pfu) over 6 hours. Cohorts 3 and 4 received a 5 Gy radiation fraction to the gross tumor volume within 24 hours of G207. Twelve subjects with progressive high-grade glioma received G207. Twenty adverse events, all grade 1, were attributed to G207. G207 was determined to be safe and tolerable in children and a recommended Phase 2 was established (1 x10^8 followed by 5 Gy radiation to the tumor). This study is a phase II, open-label, single arm clinical trial of G207 alone or combined with a single low dose of radiation in children with recurrent or progressive high grade glioma. The primary objective is to assess the efficacy. The secondary objective is to confirm the safety and tolerability of G207 and to survey for virologic shedding following G207. Subjects will receive G207 at 1 x 10^8 plaque-forming units (pfu), intratumorally via controlled rate infusion through up to 4 silastic catheters over a 6 hour period. The subject will then receive a single 5 Gy dose of radiation to the tumor within 24 hours of virus inoculation. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04482933
Study type Interventional
Source Pediatric Brain Tumor Consortium
Contact Rachel M Chon, DNP
Phone (901) 481-5848
Email rachel.chon@stjude.org
Status Not yet recruiting
Phase Phase 2
Start date June 3, 2024
Completion date February 1, 2029

See also
  Status Clinical Trial Phase
Completed NCT03826043 - THrombo-Embolic Event in Onco-hematology N/A
Terminated NCT03166631 - A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread Phase 1
Completed NCT01938846 - BI 860585 Dose Escalation Single Agent and in Combination With Exemestane or With Paclitaxel in Patients With Various Advanced and/or Metastatic Solid Tumors Phase 1
Recruiting NCT06058312 - Individual Food Preferences for the Mediterranean Diet in Cancer Patients N/A
Completed NCT03308942 - Effects of Single Agent Niraparib and Niraparib Plus Programmed Cell Death-1 (PD-1) Inhibitors in Non-Small Cell Lung Cancer Participants Phase 2
Recruiting NCT06018311 - Exercising Together for Hispanic Prostate Cancer Survivor-Caregiver Dyads N/A
Withdrawn NCT05431439 - Omics of Cancer: OncoGenomics
Completed NCT01343043 - A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma Phase 1
Completed NCT01938638 - Open Label Phase I Dose Escalation Study With BAY1143572 in Patients With Advanced Cancer Phase 1
Recruiting NCT05514444 - Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001) Phase 1
Recruiting NCT02292641 - Beyond TME Origins N/A
Terminated NCT00954512 - Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Participants With Advanced Solid Tumors (P04722, MK-7454-004) Phase 1/Phase 2
Recruiting NCT04958239 - A Study to Test Different Doses of BI 765179 Alone and in Combination With Ezabenlimab in Patients With Advanced Cancer (Solid Tumors) Phase 1
Recruiting NCT04627376 - Multimodal Program for Cancer Related Cachexia Prevention N/A
Completed NCT01222728 - Using Positron Emission Tomography to Predict Intracranial Tumor Growth in Neurofibromatosis Type II Patients
Recruiting NCT06004440 - Real World Registry for Use of the Ion Endoluminal System
Active, not recruiting NCT05636696 - COMPANION: A Couple Intervention Targeting Cancer-related Fatigue N/A
Not yet recruiting NCT06035549 - Resilience in East Asian Immigrants for Advance Care Planning Discussions N/A
Recruiting NCT06004466 - Noninvasive Internal Jugular Venous Oximetry
Not yet recruiting NCT02806557 - Profiling Neutrophil Counts in Patients on Chemotherapy N/A