NCT02062827

Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma

A Phase 1 Study of M032 (NSC 733972), a Genetically Engineered HSV-1 Expressing IL-12, in Patients With Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: University of Alabama at Birmingham · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simplex Virus-1 in patients who would not be eligible for surgical resection of recurrent glioma To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simples Virus-1 in patients who would benefit from surgical resection of recurrent glioma

Detailed description

M032 is a second-generation oncolytic herpes simplex virus (oHSV) that is conditionally replication competent; that is, similar to G207, a first generation oHSV, it can replicate in tumor cells, but not in normal cells, thus killing the tumor cells directly through this process. Replication of M032 in the tumor itself 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 carries a therapeutic payload--acting as a gene therapy vector, too--and causes the tumor cell to synthesize and secrete an immunity-stimulating protein called Interleukin-12 (IL-12) before it is killed. This IL-12 is released and promotes an immune response against surviving tumor cells, which increases the antitumor effect of the therapy. The IL-12 that is expressed can also produce an anti-angiogenic effect, by interfering with the production of new tumor blood vessels necessary to allow tumor growth. Anti-angiogenic therapies potentially starve the tumor of necessary oxygen and nutrients. Thus, the M032 oHSV produces three different potential mechanisms for antitumor effects. The virus has also been genetically-engineered to minimize the production of any toxic effects for the patient receiving the therapy.

Conditions

• Recurrent Glioblastoma Multiforme
• Progressive Glioblastoma Multiforme
• Anaplastic Astrocytoma or Gliosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	M032 (NSC 733972)	A single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

Timeline

• Start date: 2013-11-25
• Primary completion: 2022-09-01
• Completion: 2027-09-01
• First posted: 2014-02-14
• Last updated: 2025-10-02
• Results posted: 2024-02-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study