HSV-tk and XRT and Chemotherapy for Newly Diagnosed GBM

Inclusion Criteria:

• All patients must have frozen section biopsy proven anaplastic astrocytoma orglioblastoma multiforme without evidence of multifocal disease defined as multiplelesions greater than 2 cm separate from the primary treatment target, or brainsteminvolvement 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 anaplasticastrocytoma or glioblastoma demonstrated by frozen section biopsy, prior surgerywhich demonstrated anaplastic astrocytoma or glioblastoma multiforme which requiresrepeat surgery for residual tumor, but no radiation or chemotherapy has beenreceived, 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 thestudy.

• Signed informed consent to participate in the study must be obtained from patientsafter they have been fully informed of the nature and potential risks of the studyby 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 theadministration 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 followinglaboratory 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 vectortherapy 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. Discreteareas of contrast enhancement connected by abnormal T2 FLAIR signal on MRI scan arenot considered multifocal disease, as this represents a single tumor.

• Patients with brainstem involvement, in patients with leptomeningeal disease, noevidence 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 tothe spine.

• In patients with leptomeningeal disease, no bulky leptomeningeal metastases withpotential 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 proposedregimen (gene vector/Valacyclovir).

• Inability to swallow food or any condition of the upper gastrointestinal tract thatprecludes administration of oral medications (Valacyclovir).

• No active malignancy except for non-melanoma skin cancer or in situ cervical canceror treated cancer from which the patient has been continuously disease free for morethan 3 years.

• The presence of active CNS toxoplasmosis infection or Progressive MultifocalLeukoencephalopathy demonstrated on CT or MRI imaging

• The presence of active untreated cellulitis or untreated wound infections. Treatedand 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 topractice an effective method of birth control. WOCBP must have a negative serumpregnancy test within 7 days prior to the administration of the first studytreatment.

• Presence of active or suspected acute or chronic uncontrolled infection or historyof immunocompromise, including a positive HIV test result.

• Patients < 18 years of age

• Unwilling or unable to comply with the study protocol.