Clinical Trial: HSV G207 Alone or With a Single Radiation Dose in Children With Progressive or Recurrent Supratentorial Brain Tumors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I Clinical Trial of HSV G207 Alone or With a Single Radiation Dose in Children With Recurrent Supratentorial Brain Tumors

Brief 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. Funding Source - FDA OOPD

Detailed Summary:

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. 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 sensit
Sponsor: University of Alabama at Birmingham

Current Primary Outcome: Safety and Tolerability as Measured by Frequency of Grade 3 or Above Adverse Events [ Time Frame: Baseline to 15 years ]

All events with a Grade 3 or above toxicity (defined by the CTCAE v4.0) will be tabulated by event and by relationship to G207.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Immunologic Response [ Time Frame: Baseline to 12 months ]
    HSV-1 antibody titers will be checked by ELISA prior to the administration of G207 and at regular intervals after treatment.
  • Virologic Shedding [ Time Frame: Baseline to 15 years ]
    Saliva, blood and conjunctival secretions will be checked by polymerase chain reaction (PCR) and culture at regular intervals for evidence of HSV shedding and/or viremia.
  • Progression Free Survival [ Time Frame: Baseline to 24 months ]
    Time after G207 administration to clinical and radiographic disease progression will be evaluated.
  • Overall Survival [ Time Frame: Baseline to 24 months ]
    The overall survival for each patient receiving G207 will be calculated.
  • Change in Performance (Ability to Perform Normal Activities) [ Time Frame: Baseline to 12 months ]
    A modified Lansky score (for children under 16 years of age) or Karnofsky score (for children 16 and older) will be recorded and measured serially with the pre-treatment score.
  • Quality of Life (optional) [ Time Frame: Baseline to 12 months ]
    Quality of life will be measured with questionnaires taken at baseline (before administration of G207) and at specified times thereafter.


Original Secondary Outcome: Same as current

Information By: University of Alabama at Birmingham

Dates:
Date Received: May 20, 2015
Date Started: May 2016
Date Completion:
Last Updated: January 7, 2017
Last Verified: January 2017