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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 3 Years - 18 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Age ≥ 36 months and < 19 years.
  • - Pathologically proven malignant supratentorial brain tumor (including glioblastoma multiforme, giant cell glioblastoma, anaplastic astrocytoma, primitive neuroectodermal tumor, ependymoma, atypical teratoid/rhabdoid tumor, germ cell tumor, or other high-grade malignant tumor) which is progressive or recurrent despite standard care including surgery, radiotherapy, and/or chemotherapy.
A pathologically proven secondary malignant tumor without curative treatment options is eligible.
  • - Lesion must be > 1.0 cm in diameter and surgically accessible as determined by MRI.
  • - Patients must have fully recovered from acute treatment related toxicities of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study.
  • - Myelosuppressive chemotherapy: patients must have received their last dose at least 3 weeks prior (or at least 6 weeks if nitrosurea) - Investigational/Biologic agents: patients must have recovered from any acute toxicities potentially related to the agent and received last dose ≥ 7 days prior to entering this study (this period must be extended beyond the time during which adverse events are known to occur for agents with known adverse events ≥ 7 days).
For viral therapy, patients must have received viral therapy ≥ 3 months prior to study entry and have recovered from all acute toxicities potentially related to the agent.
  • - Monoclonal antibodies: patient must have received last dose ≥ 21 days prior.
  • - Radiation: Patients must have received their last fraction of craniospinal radiation (>24 Gy) or total body irradiation ≥ 3 months prior to study entry.
Patients must have received focal radiation to symptomatic metastatic sites or local palliative radiation > 28 days prior to study entry.
  • - Autologous bone marrow transplant: Patients must be ≥ 3 months since transplant prior to study entry.
  • - Normal hematological, renal and liver function (Absolute neutrophil count > 1000/mm3, Platelets > 100,000/mm3, Prothrombin Time (PT) or Partial Thromboplastin Time (PTT) < 1.3 x control, Creatinine within normal institutional limits OR > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, Total Bilirubin < 1.5 mg/dl, Transaminases < 3 times above the upper limits of the institutional norm) - Patients < 10 years, Modified Lansky score ≥ 60; patients > 10 years, Karnofsky score ≥ 60.
  • - Patient life expectancy must be at least 8 weeks.
  • - Written informed consent in accordance with institutional and FDA guidelines must be obtained from patient or legal guardian.

Exclusion Criteria:

  • - Acute infection, granulocytopenia or medical condition precluding surgery.
  • - Pregnant or lactating females.
  • - Prior history of encephalitis, multiple sclerosis, or other central nervous system (CNS) infection.
  • - Tumor involvement which would require ventricular, cerebellar or brainstem inoculation or would require access through a ventricle in order to deliver treatment.
  • - Required steroid increase within 1 week prior to injection.
  • - Known HIV seropositivity.
  • - Concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, gancyclovir, foscarnet, cidofovir) or any immunosuppressive drug therapy (except dexamethasone or prednisone).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02457845
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Gregory K. Friedman, MD
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Gregory K Friedman, M.D.
Principal Investigator Affiliation University of Alabama at Birmingham (UAB)
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, U.S. Fed
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Supratentorial Neoplasms, Malignant, Malignant Glioma, Glioblastoma, Anaplastic Astrocytoma, PNET, Cerebral Primitive Neuroectodermal Tumor, Embryonal Tumor
Additional Details

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.

Arms & Interventions

Arms

Experimental: HSV G207

Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI. If G207 is safe in the first two cohorts of patients, subsequent patients will receive a single dose of G207 infused through catheters into region(s) of tumor defined by MRI followed by a 5 Gy dose of radiation to the tumor given with 24 hours of virus inoculation. Intervention: Biological: G207

Interventions

Biological: - G207

Single dose of HSV-1 (G207) infused through catheters into region(s) of tumor defined by MRI

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Children's of Alabama, Birmingham, Alabama

Status

Address

Children's of Alabama

Birmingham, Alabama, 35233

Nationwide Children's Hospital, Columbus, Ohio

Status

Address

Nationwide Children's Hospital

Columbus, Ohio, 43205