This is an open-label, single site study to evaluate the safety and tolerability of intratumoral administration of G207 followed by treatment with radiation therapy in patients with recurrent/progressive Malignant Glioma.

This study is a two stage phase 1 study, in which a de-escalating dosing scheme will be used, i.e. the first patients will receive the higher dose and if excessive toxicity occurs, the dose will be reduced for the following patients. The purpose of the dose de-escalation phase is to find the best safe dose of G207.

In the first stage of the study, treatment with G207 will be followed by focal radiation therapy on the following day, and in the second stage treatment with G207 will be followed by gamma knife surgery also on the following day.

All patients will return to the clinic 28 days and 3, 6, 9 and 12 months after G207 administration at which time clinical assessments will be performed, and will be followed for safety and survival at clinic visits or by telephone every 3 months for up to 2 additional years and annually thereafter.

Inclusion Criteria:

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

4. Normal hematological, renal and liver function

   • Absolute neutrophil count > 1500/mm3
   • Platelets > 100,000/mm3
   • PT or 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
5. Karnofsky Performance Status score ≥ 70
6. Age > 19 years-old
7. Capable of giving informed consent
8. Must be willing to practice an effective barrier method of birth control for 2 months post G207 inoculation, whether male or female
9. Females of childbearing potential: negative pregnancy test within 24 hours prior to G207 administration

Exclusion Criteria:

1. Surgical resection within 4 weeks of enrolment
2. Acute infection, granulocytopenia or medical condition precluding surgery
3. Pregnant or lactating females
4. History of encephalitis, multiple sclerosis, or other CNS infection
5. 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/CSF dissemination
6. 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)
7. Tumor locations that would expose the patient to unacceptable risk with radiation therapy
8. Prior participant in experimental viral therapy (e.g., adenovirus, retrovirus or herpesvirus protocol)
9. Prior participant in chemotherapy, cytotoxic therapy, immunotherapy or gene therapy protocol within 6 weeks of enrolment
10. Required steroid increase within 2 weeks prior to injection
11. HIV seropositive
12. Concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscavir, cidofovir)
13. Active oral or genital herpes lesion
14. Any contraindication for undergoing MRI such as pacemakers, infusion pumps, ferromagnetic aneurysm clips, metal prostheses, etc.
15. Radiation treatment volume of greater than 4 cm maximum diameter (Stage 2 only)