HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors

Inclusion Criteria:

• Age ≥ 36 months and < 22 years

• Pathologically proven malignant cerebellar brain tumor (including medulloblastoma,glioblastoma multiforme, giant cell glioblastoma, anaplastic astrocytoma, primitiveneuroectodermal tumor, ependymoma, atypical teratoid/rhabdoid tumor, germ celltumor, or other high-grade malignant tumor) which is progressive or recurrentdespite standard care including surgery, radiotherapy, and/or chemotherapy. Apathologically proven secondary malignant cerebellar tumor without curativetreatment options is eligible.

• A review of the MRI scan will be necessary to determine if the tumor location andsize are such that the patient may be included in the study. The MRI scan must bereviewed and approved by the site neurosurgeon and/or study radiologist forenrollment. The following guidelines must be met: Lesion must be ≤ 3.0 cm indiameter and surgically accessible as determined by MRI. Larger tumors may besurgically debulked and treated if ≤ 3.0 cm after debulking. Tumor measurementsshould 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 allprior chemotherapy, immunotherapy or radiotherapy prior to the date of G207administration. All washout intervals below are measured relative to the date ofG207 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 toG207 administration

• Investigational/Biologic agents: patients must have recovered from any acutetoxicities potentially related to the agent and received last dose ≥ 7 days prior toG207 administration (this period must be extended beyond the time during whichadverse 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 G207administration and must have recovered from all acute toxicities potentially relatedto 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. Patientsmust have received focal radiation to symptomatic metastatic sites or localpalliative radiation ≥ 28 days prior to G207 administration.

• Autologous bone marrow transplant: Patients must be ≥ 3 months since transplantprior 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 >60mL/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 DrugAdministration (FDA) guidelines must be obtained from patient or legal guardian

Exclusion Criteria:

• Acute infection, granulocytopenia or medical condition precluding surgery

• Pregnant or lactating females

• Diagnosis of encephalitis or central nervous system (CNS) infection ≤ 3 months prior

• Receiving ongoing treatment for encephalitis, CNS infection or multiple sclerosis

• Tumor involvement which would require ventricular or brainstem inoculation or wouldrequire access through a ventricle in order to deliver treatment

• Patient requires an escalation in ongoing systemic corticosteroid therapy within 7days prior to G207 inoculation or requires ongoing systemic corticosteroid therapyat a dose > 2 mg/day of dexamethasone (or equivalent) at the time of inoculation.For this study, 'systemic corticosteroids' include oral, intravenous, orintramuscular formulations. A single, non-consecutive dose does not constituteexclusion. Physiologic corticosteroid replacement therapy (e.g., hydrocortisone foradrenal insufficiency) is not considered immunosuppressive and does not constituteexclusion

• Known human immunodeficiency virus (HIV) seropositivity

• Concurrent therapy with any drug active against herpes simplex virus (HSV) (acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, foscarnet,cidofovir) or any immunosuppressive drug therapy (except dexamethasone orprednisone)

• Patients with a prior or concurrent malignancy whose natural history or treatmenthas the potential to interfere with the safety or efficacy assessment of theinvestigational regimen for this trial

• Concurrent anticancer or investigational drug