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).