A Phase 1b Study of AdV-tk + Valacyclovir Gene Therapy in Combination With Standard Radiation Therapy for Malignant Gliomas

Inclusion Criteria:

- Presumed malignant glioma based on clinical and radiologic evaluation (pathologic
confirmation of malignant glioma must be made at the time of stereotactic biopsy or
resection prior to AdV-tk injection; if this is not possible, the injection will not
be performed and the subject will no longer be eligible for the study).

- Tumor must be accessible for injection and must not be located in the brainstem,
midbrain, contained within the ventricular system, or located in an infratentorial
location.

- Patients must be planning to undergo standard radiation therapy.

- Patients must be 18 years of age or older.

- Performance status must be KPS > or equal to 70.

- Patients must have SGOT (AST) < 3x upper limit of normal.

- Patients must have serum creatinine < 2mg/dl and calculated creatinine clearance
>10ml/min.

- Patients must have platelets > 100,000/mm3 and WBC > 3000/mm3.

- Patients of reproductive age must agree to use a medically accepted form of birth
control while on the study.

- Patients must give study specific informed consent prior to enrollment.

- Patients must be able to tolerate MRI scan procedure

Exclusion Criteria:

- Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection
but not to exclude patients with a distant history of resolved hepatitis A infection.

- Patients on immunosuppressive drugs (with exception of corticosteroid)

- Known HIV+ patients.

- Patients with acute infections (viral, bacterial or fungal infections requiring
therapy).

- Pregnant or breast feeding patients. Female patients of childbearing age must have
negative serum or urine pregnancy test within 1 week of beginning therapy.

- Evidence of metastatic disease or other malignancy (except squamous or basal cell
skin cancers).

- Prior radiation therapy to the brain or prior treatment for brain tumor (except prior
biopsy or subtotal resection).

- Other serious co-morbid illness or compromised organ function.

- Patients may not receive temozolomide until valacyclovir completed and may not
receive other investigational anti-tumor agents within 30 days prior to study entry
or during active participation in the study (defined as from study entry until tumor
progression).