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, 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.
• Lesion must be ≥ 1.0 cm ≤ 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
• 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: 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 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 creatinine clearance >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 < 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 be obtained 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 ongoing treatment for encephalitis, CNS infection or multiple sclerosis
• Tumor involvement which would require ventricular or brainstem inoculation or would require access through a ventricle in order to deliver treatment
• Required steroid increase within 1 week prior to G207 inoculation or patients requiring >2 mg of dexamethasone daily
• Known HIV seropositivity
• Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, gancyclovir, foscarnet, cidofovir) or any immunosuppressive drug therapy (except dexamethasone or prednisone).
• Other current malignancy
• Concurrent anticancer or investigational drug