A Staged Phase 1 Study of the Treatment of Malignant Glioma With G207, a Genetically Engineered HSV-1, Followed by Radiation Therapy

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 magnetic resonance imaging (MRI)

4. 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

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 central nervous system (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/cerebral
spinal fluid (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 herpes simplex virus (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)