A Phase IB 2 Dose Trial of IRS-1 HSV C134 (IND 17296) Administered Intratumorally in Patients With Recurrent Malignant Glioma

Inclusion Criteria: * Patients must have histologically or cytologically confirmed recurrent/progressive glioblastoma multiforme, Grade 3 or Grade 4 astrocytoma, or gliosarcoma. * Prior therapy. Patients must have failed a course of external beam radiotherapy to the brain at least 4 weeks prior to enrollment. * Age ≥18 years. Because no dosing or adverse event data are currently available on the use of C134 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)/ALT(SGPT) ≤ 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 in diameter as determined by MRI. * The effects of C134 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 C134. Because it is currently unknown if C134 can be transmitted by sexual contact, a barrier method of birth control should be employed. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. * 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 initial C134 administration. Whenever possible, the patient should be on a steroid dose that is equivalent to a dexamethasone dose of ≤ 2mg daily at study entry and initial treatment. Exclusion Criteria: * Patients who have had chemotherapy, cytotoxic therapy, immunotherapy or gene therapy within 6 weeks prior to entering the study, surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy at any time (e.g., adenovirus, retrovirus or herpesvirus\* protocol unless approved by DSMB). Also, those 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 (except C134 per protocol). * Enhancing tumor diameter larger than 5.5 cm for initial treatment or subsequent treatment if only stereotactic biopsy is planned. If resection is planned at the time of second treatment, there is no limit to tumor size at that time. In other words, if the tumor enlarges from less than 5.5 cm to larger than 5.5 cm during the interval between treatment one and two, as long as a resection is planned along with treatment two, no limit in size is present (Note: this size limitation has been derived from experience with prior oHSV therapeutics in malignant glioma). * History of allergic reactions or CTCAE version 5.0 Grade IV toxicity attributed to C134 or compounds of similar biologic composition to C134. * Tumor involvement which would require ventricular, brainstem, basal ganglia, occipital lobe, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment. Additionally, patients with bilateral enhancing tumor are not eligible. * Prior history of encephalitis, multiple sclerosis. Patient with other active CNS infections are also excluded. * Active oral herpes lesion. * Concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, 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. * Required steroid increase within 2 weeks of initial scheduled C134 administration. When possible, the patient should be on a dexamethasone equivalent dose of ≤ 2mg daily at the time of treatment. * Known history of allergic reaction to IV contrast material that is not amenable to pre-treatment by UAB protocol. * Have a pacemaker, ferro-magnetic aneurysm clips, metal infusion pumps, metal or shrapnel fragments, or certain types of stents that preclude MRI. * Received Bevacizumab (Avastin) therapy within 4 weeks of scheduled C134 administration. Excluded patient groups: * Pregnant women are excluded from this study because C134 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 C134 breastfeeding should be discontinued if the mother is treated with C134. * Immune deficient, 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.