G207 Followed by Radiation Therapy in Malignant Glioma

Inclusion criteria

• Pathologically proven residual/recurrent glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma which is progressive despite radiotherapy or chemotherapy
• Failed external beam radiotherapy > 5,000 CGy at least 4 weeks prior to enrollment
• Residual/recurrent lesion must be ≥ 1.0 cm and (for Stage 2 only) ≤ 4 cm in diameter as determined by magnetic resonance imaging (MRI)
• Normal hematological, renal and liver function

• Absolute neutrophil count > 1500/mm3
• Platelets > 100,000/mm3
• Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.3 x control
• Creatinine < 1.7 mg/dl
• Total bilirubin < 1.5 mg/dl
• Transaminases < 4 times above the upper limits of the institutional norm
• Karnofsky Performance Status score ≥ 70
• Age > 19 years-old
• Capable of giving informed consent
• Must be willing to practice an effective barrier method of birth control for 2 months post G207 inoculation, whether male or female
• Females of childbearing potential: negative pregnancy test within 24 hours prior to G207 administration

Exclusion criteria

• Surgical resection within 4 weeks of enrolment
• Acute infection, granulocytopenia or medical condition precluding surgery
• Pregnant or lactating females
• History of encephalitis, multiple sclerosis, or other central nervous system (CNS) infection
• Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment or tumor involving both hemispheres or with subependymal/cerebral spinal fluid (CSF) dissemination
• Tumor position that could, in the Investigator's opinion, pose the risk of penetration of the cerebral ventricular system during inoculation with the study drug (Note: If penetration of the ventricular system is suspected or confirmed, G207 administration must be aborted.)
• Tumor locations that would expose the patient to unacceptable risk with radiation therapy
• Prior participant in experimental viral therapy (e.g., adenovirus, retrovirus or herpesvirus protocol)
• Prior participant in chemotherapy, cytotoxic therapy, immunotherapy or gene therapy protocol within 6 weeks of enrolment
• Required steroid increase within 2 weeks prior to injection
• HIV seropositive
• Concurrent therapy with any drug active against herpes simplex virus (HSV) (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscavir, cidofovir)
• Active oral or genital herpes lesion
• Any contraindication for undergoing MRI such as pacemakers, infusion pumps, ferromagnetic aneurysm clips, metal prostheses, etc.
• Radiation treatment volume of greater than 4 cm maximum diameter (Stage 2 only)