Combined Cytotoxic and Immune-Stimulatory Strategy in Treating Patients with High-Grade Glioma That Can Be Removed by Surgery

Inclusion Criteria

• Newly diagnosed supratentorial brain lesion compatible with a high grade glioma (WHO III or IV) by magnetic resonance (MR) with no prior treatment with either gene therapy, chemotherapy or radiation treatments that is amenable to attempted gross total resection (GTR); “high grade glioma” can include: glioblastoma multiforme (WHO grade IV); anaplastic astrocytoma (WHO grade III); anaplastic oligodendroglioma (WHO grade III); and anaplastic ependymoma (WHO grade III)
• Intraoperative histological frozen section at the time of tumor resection compatible with high-grade glioma or malignant glioma; if intraoperative diagnosis is not compatible with high grade glioma, the patient will not be enrolled
• Karnofsky performance status (KPS) >= 70
• Absolute neutrophil count (ANC) >= 1,500 cells/mm3 (within 14 days prior)
• Platelets >= 100,000 cells/mm3 (within 14 days prior)
• Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) >= 10.0 g/dl is acceptable) (within 14 days prior)
• Blood urea nitrogen (BUN) =< 30 mg/dl within 14 days prior
• Creatinine =< 1.7 mg/dl within 14 days prior
• Bilirubin =< 2.0 mg/dl within 14 days prior
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3x laboratory upper limit of normal within 14 days prior
• Both genders must use contraception if of reproductive capacity
• For women of childbearing age, a negative pregnancy test performed within 14 days of surgery
• Capable of informed consent

Exclusion Criteria

• Diffusely multifocal lesion
• Lesions not amenable to GTR
• Tumors infiltrate the cerebellum, bilateral corpus callosum (“butterfly glioma”), ventricular system, or brain stem
• Infratentorial high grade glioma
• History of primary central nervous system (CNS) disease that would interfere with subject evaluation
• History of current diagnosis of other cancer except curative cervical cancer in situ, basal or squamous cell carcinoma of the skin
• Evidence of other significant disease including hematologic, renal or liver disease that is not explained by the patient’s current medical condition or concomitant disease, (i.e. levels of absolute neutrophil count [ANC], hemoglobin, platelets, clotting time, serum creatinine, etc)
• Human immunodeficiency virus (HIV), hepatitis B, hepatitis C
• Active systemic infection
• Immuosuppressive disorders (chronic steroid therapy, acquired or congenital immune deficiency syndromes, autoimmune disease)
• Serious medical conditions (congestive heart failure [CHF], angina, diabetes mellitus type 1, chronic obstructive pulmonary disease [COPD], bleeding diathesis)
• Any contraindication for undergoing magnetic resonance imaging (MRI)
• Pregnant or lactating females
• Unacceptable anesthesia risk
• Evidence of bleeding diathesis or use of anticoagulant medication or any medication that may increase the risk of bleeding that cannot be stopped prior to surgery
• Prior gene therapy
• Allergy to valacyclovir or unable to take oral tablets