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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
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.
Children's of Alabama
Birmingham, Alabama, United States
ACTIVE_NOT_RECRUITINGSt. Louis Children's Hospital
St Louis, Missouri, United States
ACTIVE_NOT_RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGSafety and Tolerability as Measured by Frequency of Grade 3 or Above Adverse Events
All events with a Grade 3 or above toxicity (defined by the CTCAE v5.0) will be tabulated by event and by relationship to G207.
Time frame: Baseline to 15 years
Immunologic Response
HSV-1 antibody titers will be checked by ELISA prior to the administration of G207 and at regular intervals after treatment.
Time frame: Baseline to 24 months
Virologic Shedding
HSV-1 antibody titers will be checked by ELISA prior to the administration of G207 and at regular intervals after treatment.
Time frame: Baseline to 15 years
Progression Free Survival
Time after G207 administration to clinical and radiographic disease progression will be evaluated.
Time frame: Baseline to 24 months
Overall Survival
The overall survival for each patient receiving G207 will be calculated
Time frame: Baseline to 60 months
Change in Performance (Ability to Perform Normal Activities)
A modified Lansky score (for children under 16 years of age) or Karnofsky score (for children 16 and older) will be recorded pre-treatment and measured serially at regular intervals after treatment. The score is a standard performance score that measures overall function of the child with a scale range from 0 (lowest, poorest performance score) to 100 (highest, best performance).
Time frame: Baseline to 24 months
Quality of Life (optional)
Quality of life will be measured with questionnaires taken at baseline (before administration of G207) and at specified times thereafter.
Time frame: Baseline to 24 months
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