NCT03911388

HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors

Phase 1 Trial of Engineered HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 3 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

This study is a clinical trial to determine the safety of inoculating G207 (an experimental virus therapy) into a recurrent or refractory cerebellar brain tumor. The safety of combining G207 with a single low dose of radiation, designed to enhance virus replication, tumor cell killing, and an anti-tumor immune response, will also be tested. Funding Source- FDA OOPD

Detailed description

Outcomes for children with recurrent or progressive cerebellar malignant brain tumors are very poor, and there are a lack of effective salvage therapies once a patient fails standard treatments. 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 "one-two punch" at attacking 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. The safety of G207 has been demonstrated in 3 phase I clinical trials involving adults with supratentorial high-grade gliomas adults at the University of Alabama (UAB) and in an ongoing (closed to accrual) phase I clinical trial involving children with recurrent supratentorial brain tumors at Children's of Alabama. In the adult 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 anti-tumor responses have been seen. Preclinical laboratory studies have demonstrated that a variety of aggressive pediatric brain tumor types are sensitive to G207. This study is a phase I, open-label, single institution clinical trial of G207 alone or combined with a single low dose of radiation in children and young adults, ages 3 to 21 years, with recurrent or progressive cerebellar brain tumors. The primary goal is to determine safety. The secondary aims are to obtain preliminary information on the effectiveness of and immune response to G207. A traditional 3 + 3 design will be used with four patient cohorts. The first cohort will receive G207 alone, and the next cohorts will receive G207 at one of three doses followed by a 5 Gy dose of radiation to active areas of tumor.

Conditions

• Neoplasms, Brain
• Glioblastoma Multiforme
• Glioblastoma of Cerebellum
• Neoplasms
• Astrocytoma
• Astrocytoma, Cerebellar
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Cerebellar PNET, Childhood
• Cerebellar Neoplasms
• Cerebellar Neoplasms, Primary
• Cerebellar Neoplasm, Malignant
• Cerebellar Neoplasm Malignant Primary
• Neoplasm Metastases
• Neoplasm Malignant
• Neoplasms, Neuroepithelial
• Neoplasms, Germ Cell and Embryonal
• Neoplasms by Histologic Type
• Neoplasms, Glandular and Epithelial
• Neoplasms, Nerve Tissue
• Central Nervous System Neoplasms, Primary
• Central Nervous System Neoplasms, Malignant
• Nervous System Neoplasms
• Neoplasms by Site
• Brain Diseases
• Central Nervous System Diseases
• Nervous System Diseases
• Medulloblastoma Recurrent
• HSV
• Virus
• Pediatric Brain Tumor
• Nervous System Cancer
• Primitive Neuroectodermal Tumor (PNET) of Cerebellum

Interventions

Type	Name	Description
BIOLOGICAL	G207	Single dose of G207 infused through catheters into region(s) of tumor. If G207 is safe in the first cohort of patients, subsequent patients will receive a single dose of G207 infused through catheters into region(s) of tumor followed by a 5 Gy dose of radiation to the tumor (which includes progressive leptomeningeal disease or any site of gross tumor progressing in the brain parenchyma) within 24 hours of virus inoculation.

Timeline

• Start date: 2019-09-12
• Primary completion: 2026-09-01
• Completion: 2027-09-01
• First posted: 2019-04-11
• Last updated: 2026-04-13

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study