HSV-tk and XRT and Chemotherapy for Newly Diagnosed GBM

Inclusion Criteria:

* All patients must have frozen section biopsy proven anaplastic astrocytoma or glioblastoma multiforme without evidence of multifocal disease defined as multiple lesions greater than 2 cm separate from the primary treatment target, or brainstem involvement as well as radiographic evidence consistent with these diagnoses.
* Life expectancy ≥ 12 weeks.

  \- Patient can receive second treatment of HSV-tk after 6 months
* Patients should have the following characteristics: newly diagnosed anaplastic astrocytoma or glioblastoma demonstrated by frozen section biopsy, prior surgery which demonstrated anaplastic astrocytoma or glioblastoma multiforme which requires repeat surgery for residual tumor, but no radiation or chemotherapy has been received, ECOG performance status of 0-1. No evidence of other active malignancy (except squamous or basal cell skin cancers).
* Patients with leptomeningeal disease may be considered for enrollment into the study.
* Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks of the study by the investigator (or his/her designee) with the aid of written information.
* Willing to provide biopsies as required by the study.
* WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment. Women must not be lactating.
* WOCBP and men must practice an effective method of birth control
* Patients must have adequate baseline organ function as assessed by the following laboratory values before initiating the protocol:
* serum creatinine \< 1.5 mg/dL
* T. bilirubin \< 2.5 mg/dL, ALT, AST, GGT and Alk Phos \< 2 x normal
* Platelet count \> 100,000/ml , ANC\> 1500/ml , Hgb\> 10 gm/dL
* Normal partial thromboplastin time (PTT) and Pro-Thrombin Time (PT)

Exclusion Criteria:

* Prior treatment with immunomodulatory therapy, immunotherapy, and/or gene vector therapy in the past 3 months.
* Any cytotoxic chemotherapy, RT, or immunotherapy or any investigational drug within 3 weeks of study treatment start.
* Evidence of substantial multifocal disease defined as multiple lesions greater than 2cm separate from the primary treatment target, or brainstem involvement. Discrete areas of contrast enhancement connected by abnormal T2 FLAIR signal on MRI scan are not considered multifocal disease, as this represents a single tumor.
* Patients with brainstem involvement, in patients with leptomeningeal disease, no evidence of diffuse disease or spread to the spine.
* Patients on immunosuppressive drugs (other than steroids for brain edema).
* In patients with leptomeningeal disease, no evidence of diffuse disease or spread to the spine.
* In patients with leptomeningeal disease, no bulky leptomeningeal metastases with potential to obstruct CSF flow will not be enrolled.
* Liver disease, such as cirrhosis or active/chronic hepatitis B or C.
* History of or current alcohol misuse/abuse within the past 12 months.
* Known or suspected allergy or hypersensitivity to any component of the proposed regimen (gene vector/Valacyclovir).
* Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (Valacyclovir).
* No active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated cancer from which the patient has been continuously disease free for more than 3 years.
* The presence of active CNS toxoplasmosis infection or Progressive Multifocal Leukoencephalopathy demonstrated on CT or MRI imaging
* The presence of active untreated cellulitis or untreated wound infections. Treated and resolving cellulitis and infections are not an exclusion criteria.
* Active IV drug abuse or severe opioid abuse
* Pregnant or breastfeeding women or women/men able to conceive and unwilling to practice an effective method of birth control. WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment.
* Presence of active or suspected acute or chronic uncontrolled infection or history of immunocompromise, including a positive HIV test result.
* Patients \< 18 years of age
* Unwilling or unable to comply with the study protocol.