Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma

Inclusion Criteria * Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma. * Prior therapy: Patients must have failed external beam radiotherapy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy. All radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment. * Age ≥18 years (age of majority for clinical trials in Alabama). Because no dosing or adverse event data are currently available on the use of M032 in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials. * Karnofsky Performance Status ≥70% * Life expectancy of greater than 4 weeks. * Patients must have normal organ and marrow function as defined below: * Leukocytes: \>3,000/μl * absolute neutrophil count: \>1,500/μl * platelets: \>100,000/μl * total bilirubin within normal institutional limits * AST(SGOT)(aspartate aminotransferase)/ALT(SGPT)(alanine aminotransferase): \<2.5 X institutional upper limit of normal * creatinine within normal institutional limits OR * creatinine clearance: \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. * Residual lesion must be ≥1.0 cm and \< 5.5 cm in diameter without bilateral extension through the corpus callosum as determined by MRI as this is a locally delivered treatment. These parameters will be re-evaluated on imaging done on the day of catheter implantation and if the lesion no longer meets. * The effects of M032 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the first six months after receiving M032. Because it is currently unknown if M032 can be transmitted by sexual contact, a barrier method of birth control must be employed and for six (6) months following the administration of the study drug. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. For two weeks after receiving M032, subjects should avoid intimate contact with pregnant women, infants and young children and individuals with decreased immunity (ability to fight infection). Subjects should also refrain from donating blood during the trial * Ability to understand and the willingness to sign a written informed consent document. * Females of childbearing potential must not be pregnant; this will be confirmed by a negative serum pregnancy test within 14 days prior to starting study treatment. * Steroid use is allowed as long as dose has not increased within 2 weeks of scheduled M032 administration. Whenever possible, the patient should be on a steroid dose that is equivalent to a dexamethasone dose of ≤ 2mg daily at the time of treatment. Exclusion Criteria * Patients who have had chemotherapy, cytotoxic therapy, immunotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas), surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy or gene therapy at any time (e.g., adenovirus, retrovirus or herpes virus protocol). However, this does not preclude re-treatment with M032 at a later date. * Patients who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier. * Patients may not be receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar biologic composition to M032 or to IL-12. * Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment. Also, since M032 is a local treatment, patients whose tumors have bilateral extension through the corpus callosum, those with actively growing multifocal disease by MRI, and/or CSF dissemination/ leptomeningeal disease, are ineligible. * Prior history of encephalitis, multiple sclerosis, or other CNS infection. * Required steroid increase within 2 weeks of scheduled M032 administration. When possible, the patient should be on a dexamethasone equivalent dose of ≤ 2mg daily at the time of treatment. * Active oral herpes lesion. * Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, gancyclovir, foscarnet, cidofovir). * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other medical condition that precludes surgery. Also, psychiatric illness/social situations that would limit compliance with study requirements. * Excluded patient groups * Pregnant women are excluded from this study because M032 is a viral oncolytic therapy with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M032, breastfeeding women will not be included in the study. * Because patients with immune deficiency will be unable to mount the anticipated immune response underlying this therapeutic rationale, HIV-seropositive patients are excluded from this study. Other treatment studies for this disease that are less dependent on the patients' immune response are more appropriate for HIV-seropositive patients. * Patients with known history of allergic reaction to IV contrast material that is not amenable to pre-treatment by University of Alabama at Birmingham protocol. * Patients with pacemakers, ferro-magnetic aneurysm clips, metal infusion pumps, metal or shrapnel fragments or certain types of stents. * Receipt of Gliadel Therapy. * (Receipt of Bevacizumab (Avastin) therapy within 4 weeks of scheduled M032 administration. (Receipt of Bevacizumab (Avastin) greater than 4 weeks of scheduled M032 administration does not exclude patient.) * Any other reason the investigator deems subject is unfit for participation in the study.