Phase 1b Study of AdV-tk + Valacyclovir Combined With 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).