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.

• Lesion must be ≥ 1.0 cm ≤ 3.0 cm in diameter and surgically accessible as determinedby MRI. Larger tumors may be surgically debulked and treated if ≤ 3.0 cm afterdebulking

• Patients must have fully recovered from acute treatment related toxicities of allprior 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 acutetoxicities potentially related to the agent and received last dose ≥ 7 days prior toentering this study (this period must be extended beyond the time during whichadverse 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 tostudy entry and have recovered from all acute toxicities potentially related to theagent.

• Monoclonal antibodies: The 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 musthave received focal radiation to symptomatic metastatic sites or local palliativeradiation ≥ 28 days prior to study entry.

• Autologous bone marrow transplant: Patients must be ≥ 3 months since transplantprior to study entry.

• Normal hematological, renal and liver function (absolute neutrophil count > 1000/mm3, platelets > 100,000/mm3, prothrombin time (PT) or partial thromboplastintime (PTT) < 1.3 x control, creatinine within normal institutional limits ORcreatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels aboveinstitutional normal, total bilirubin < 1.5 mg/dl, transaminases < 3 times above theupper limits of the institutional norm)

• Patients < 16 years, Modified Lansky performance score ≥ 60; patients ≥ 16 years,Karnofsky performance score ≥ 60

• Patient life expectancy must be at least 8 weeks

• Written informed consent in accordance with institutional and FDA guidelines must beobtained from patient or legal guardian

Exclusion Criteria:

• Any treatment outside the allowable guidelines outlined in section 5.1.

• Diffuse, widespread, abnormal tumor pattern involving 3 or more lobes of the brain

• Acute infection, granulocytopenia or medical condition precluding surgery

• Pregnant or lactating females

• Diagnosis of encephalitis or CNS infection < 3 months prior, or receiving ongoingtreatment 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

• Required steroid increase within 1 week prior to G207 inoculation or patientsrequiring >2 mg of dexamethasone daily

• Known HIV seropositivity

• Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir,penciclovir, famciclovir, gancyclovir, foscarnet, cidofovir) or anyimmunosuppressive drug therapy (except dexamethasone or prednisone).

• Other current malignancy

• Concurrent anticancer or investigational drug