Inclusion Criteria

• Has given written informed consent
• Is between 18 and 75 years old, inclusive
• Must have histologically proven Glioblastoma or Anaplastic Astrocytoma in first or second recurrence (including this recurrence) or progression following initial definitive multimodal therapy with surgery, temozolomide (unless MGMT promoter unmethylated) and radiation (confirmed by diagnostic biopsy with local pathology review or contrast enhanced MRI)
• If first recurrence of Glioblastoma is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either
  • Histopathologic confirmation of recurrent tumor
  • New enhancement on MRI outside of the radiotherapy treatment field
• Must have measurable disease preoperatively, defined as
  • At least 1 contrast enhancing lesion
  • Measuring at least 1 cm in 2 planes (axial, coronal, or sagittal)
• Must be at least 4 weeks post last dose of temozolomide
• Prior gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is allowed but must have either histopathologic confirmation of recurrent tumor, or new enhancement on MRI outside of the radiotherapy treatment field
• Based on the pre operative evaluation by neurosurgeon is a candidate for ≥ 80% resection of enhancing region
• IDH mutation status of the primary tumor must be available or tumor samples must be available for pre randomization testing
• Laboratory values adequate for patient to undergo surgery, including
  • Platelet count ≥ 60,000/mm3
  • Hgb ≥ 10 g/dL
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Absolute lymphocyte count (ALC) ≥ 500/mm3
  • Adequate liver function, including
    • Total bilirubin ≤ 1.5 x ULN (unless has Gilbert's syndrome)
    • ALT ≤ 2.5 x ULN 
  • Estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft Gault formula
• Women of childbearing potential
  • Defined as not having ≥ 12 months of non-therapy-induced amenorrhea or are not surgically sterile
  • Must have had a negative serum pregnancy test within the past 21 days 
  • Must use a birth control method in addition to barrier methods (condoms)
• Willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer
• Has a KPS ≥ 70
• Is willing and able to abide by the protocol

Exclusion Criteria

• History of more than 2 prior recurrences (including this recurrence) of Glioblastoma or Anaplastic Astrocytoma
• History of other malignancy, unless the patient has been disease free for at least 5 years
  • Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment
• Has histologically confirmed oligodendroglioma or mixed glioma
• Known 1p/19q co deletion
• Has a contrast enhancing brain tumor that is any of the following
  • Multi focal defined as 2 separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid attenuated inversion recovery (FLAIR) or T2 sequences
  • Associated with either diffuse subependymal or leptomeningeal dissemination
  • > 5 cm in any dimension
• Has or had any active infection requiring antibiotic, antifungal or antiviral therapy within the past 4 weeks
• Has any bleeding diathesis, or must take anticoagulants or antiplatelet agents including nonsteroidal anti inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be stopped for surgery
• Is HIV positive
• Has a history of allergy or intolerance to flucytosine
• Has a gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine
• Has received cytotoxic chemotherapy within the past 4 weeks (6 weeks for nitrosoureas) of the planned surgery date
• Has received any investigational treatment within the past 30 days or prior immunotherapy or antibody therapy within the past 45 days
• Is breast feeding
• Intends to undergo treatment with the Gliadel® wafer at the time of this surgery or has received the Gliadel® wafer < 30 days from W1D1 (surgery)
• Has received bevacizumab for disease unless in the context of primary therapy for newly diagnosed glioma
• If planning to potentially receive bevacizumab, has no evidence of uncontrolled hypertension (defined as a blood pressure of ≥ 150 mm Hg systolic and/or ≥ 100 mm Hg diastolic on medication) or active GI perforation
• Has received systemic dexamethasone continuously at a dose > 8 mg/day for 8 weeks prior to the date of the screening assessment
• Severe pulmonary, cardiac or other systemic disease, specifically
  • New York Heart Association > Grade 2 congestive heart failure within 6 months prior to study entry, unless asymptomatic and well controlled with medication
  • Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ≥ Grade 2 dyspnea, according to CTCAE 4.03)
  • Has any other disease, either metabolic or psychological, which as per Investigator assessment may affect compliance or place  at higher risk of potential treatment complications