Phase 1 Trial of Engineered HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
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
• Age ≥ 36 months and \< 22 years
• Pathologically proven malignant cerebellar brain tumor (including medulloblastoma, 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 cerebellar tumor without curative treatment options is eligible.
• A review of the MRI scan will be necessary to determine if the tumor location and size are such that the patient may be included in the study. The MRI scan must be reviewed and approved by the site neurosurgeon and/or study radiologist for enrollment. The following guidelines must be met: Lesion must be ≤ 3.0 cm in diameter and surgically accessible as determined by MRI. Larger tumors may be surgically debulked and treated if ≤ 3.0 cm after debulking. Tumor measurements should be confirmed on the Immunotherapy Response Assessment in Neuro-Oncology (iRANO) form or the institutional MRI report
• Patients must have fully recovered from acute treatment-related toxicities of all prior chemotherapy, immunotherapy or radiotherapy prior to the date of G207 administration. All washout intervals below are measured relative to the date of G207 administration.
• Myelosuppressive chemotherapy: patients must have received their last dose at least 3 weeks prior (or at least 6 weeks if nitrosurea) to G207 administration.
• Monoclonal antibodies: patient must have received the last dose ≥ 21 days prior to G207 administration
• Investigational/Biologic agents: patients must have recovered from any acute toxicities potentially related to the agent and received last dose ≥ 7 days prior to G207 administration (this period must be extended beyond the time during which adverse events are known to occur for agents with known adverse events ≥\>= 7 days).
• Viral therapy: Patients must have received viral therapy ≥ 3 months prior to G207 administration and must have recovered from all acute toxicities potentially related to the agent
• Radiation: Patients must have received their last fraction of craniospinal radiation (\>24 Gy) or total body irradiation ≥ 3 months prior to G207 administration. Patients must have received focal radiation to symptomatic metastatic sites or local palliative radiation ≥ 28 days prior to G207 administration.
• Autologous bone marrow transplant: Patients must be ≥ 3 months since transplant prior to G207 administration.
• Absolute neutrophil count \> 1000/mm3
• Platelets ≥ 100,000/mm\^3
• Prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.3 x control
• Creatinine within normal institutional limits OR creatinine clearance \>60 mL/min/1.73 m\^2 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 \< 16 years, Modified Lansky performance score ≥ 60; patients ≥ 16 years, Karnofsky performance score ≥ 60
• Written informed consent in accordance with institutional and Food and Drug Administration (FDA) guidelines must be obtained from patient or legal guardian