HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors
Condition: Supratentorial Neoplasms, Malignant; Malignant Glioma; Glioblastoma; Anaplastic Astrocytoma; PNET; Cerebral Primitive Neuroectodermal Tumor; Embryonal Tumor
MeSH terms: Neoplasms; Glioblastoma; Glioma; Brain Neoplasms; Astrocytoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Supratentorial Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is a clinical trial to determine the safety of injecting G207 (a new experimental
      virus therapy) into a recurrent or progressive brain tumor. The safety of combining G207 with
      a single low dose of radiation, designed to enhance virus replication and tumor cell killing,
      will also be tested.
    

Detailed description: 
      Outcomes for children with recurrent or progressive supratentorial 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 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. A maximum tolerated dose was not reached in all 3 trials.
      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.

      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 with recurrent or progressive
      supratentorial 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 two cohorts will
      receive G207 at one of two doses, and the second two cohorts will receive G207 at one of two
      doses followed by a 5 Gy dose of radiation.
    

Intervention name(s): G207
Intervention type(s): Biological
Intervention description(s): Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Brain Tumor, Recurrent; Glioma; Glioblastoma; Gliosarcoma; Anaplastic Astrocytoma; Oligodendroglioma; Rhabdoid Tumor; Cerebral Primitive Neuroectodermal Tumor; PNET; Ependymoma; Germ Cell Tumor; Choroid Plexus Carcinoma; Oncolytic Virus Therapy; Virotherapy, Oncolytic; Immunotherapy; Central Nervous System Agents; Antineoplastic Agents; Neoplasms; Pediatric; Pediatrics; Embryonal Tumor; Oncolytic; Virus; HSV; Herpes Virus