Testing the Addition of an Anti-cancer Viral Gene Therapy, Toca 511/Toca FC, to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed Glioblastoma

Inclusion Criteria:

• Presumptive diagnosis of glioblastoma based on magnetic resonance imaging (MRI)imaging within 14 days prior to registration.

• NOTE: Patients who undergo treatment with Toca 511 whose final pathology showsdiagnosis other than glioblastoma (e.g. anaplastic astrocytoma oroligodendroglioma or any other histology) will be treated with Toca FC andchemoradiation; however they will not be analyzed in the primary endpoint. Theoutcomes of these patients will be reported descriptively. Similarly the patientswith anaplastic astrocytoma or oligodendroglioma or any other histology treatedon the standard-of-care arm will be reported separately and they are allowed toreceive the treatment per choice of the treating physician/ investigator (fore.g. radiation therapy [RT] plus temozolomide or RT plusprocarbazine-lomustine-vincristine [PCV])

• In addition, patients who have undergone biopsy with diagnosis of glioblastoma and whohave never received any chemotherapy and/or radiation and are candidates for >= 80%resection of enhancing region are eligible

• The tumor must be unifocal, confined to the supratentorial compartment and based onthe pre-operative evaluation, the patient is a candidate for >= 80% resection ofenhancing region

• Measurable disease preoperatively, defined as at least 1 contrast enhancing lesion,with 2 perpendicular measurements of at least 1 cm, as per Response Assessment inNeuro-Oncology (RANO) criteria

• The hematoxylin and eosin (H&E) slide and formalin-fixed paraffin-embedded (FFPE)tumor tissue block must be available to be sent for mandatory central pathology reviewafter registration

• Patients must be able to undergo an evaluation by MRI within 96 hours post surgery toassess extent of resection

• Karnofsky performance status >= 70 within 14 days prior to registration

• History/physical examination within 14 days prior to registration

• Platelet count >= 100,000/mm^3 (within 14 days prior to registration)

• Hemoglobin (Hgb) >= 10 g/dL (within 14 days prior to registration)

• Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 14 days prior to registration)

• Absolute lymphocyte count (ALC) >= 1000/mm^3 (within 14 days prior to registration)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless has Gilbert?s syndrome) (within 14 days prior to registration)

• Alanine aminotransferase (ALT) =< 2.5 x ULN (within 14 days prior to registration)

• Estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft Gaultformula (within 14 days prior to registration)

• Women of childbearing potential (women who have not had >=12 months of non therapyinduced amenorrhea or are not surgically sterile) must have had a negative serumpregnancy test within 14 days prior to registration and must agree to use a birthcontrol method in addition to barrier methods (condoms or diaphragm) during treatmentwith temozolomide

• If the patient is randomized to arm 2, the patient or patient?s partner must bewilling to use barrier method of contraception for 12 months after receiving Toca 511and 1 month after stopping Toca FC or until there is no evidence of the virus in thepatient?s blood, whichever is longer

• The patient or a legally authorized representative must provide study-specificinformed consent prior to registration

Exclusion Criteria:

• History of prior invasive malignancy (except non-melanomatous skin cancer) unlessdisease free for a minimum of 3 years

• A contrast enhancing brain tumor on MRI that is any of the following:

• Multi focal (defined as 2 separate areas of contrast enhancement measuring atleast 10 mm in 2 planes that are not contiguous on either fluid attenuatedinversion recovery [FLAIR] or T2 hyperintensity);

• Associated with either diffuse subependymal or leptomeningeal dissemination; or

• > 50 mm in any dimension

• Active infection (excluding skin or toenail infections) requiring systemic antibiotic,antifungal or antiviral therapy within 28 days prior to registration

• Bleeding diathesis, or must take anticoagulants, or antiplatelet agents, includingnonsteroidal anti inflammatory drugs (NSAIDs), at the time of the scheduled resectionthat cannot be stopped for surgery

• Known human immunodeficiency virus (HIV) positive status

• History of allergy or intolerance to flucytosine

• Swallowing difficulty that would prevent patient from being able to swallow eithertemozolomide or Toca FC or severe active mal-absorption

• Patients who are breast feeding or lactating

• Intent to undergo treatment with the Gliadel wafer at the time of this surgery or hasreceived the Gliadel

• Prior to registration, steroid treatment beyond a maximum of 8 mg/day of dexamethasone (or equivalent) or a total of 8 weeks (56 days) is excluded

• Severe pulmonary, cardiac or other systemic disease, specifically:

• New York Heart Association > =Class II congestive heart failure within 6 months (180 days) prior to registration, unless asymptomatic and well controlled withmedication

• Uncontrolled or significant cardiovascular disease, clinically significantventricular arrhythmia (such as ventricular tachycardia, ventricularfibrillation, or Torsades de pointes), clinically significant pulmonary disease (such as >= grade 2 dyspnea)

• Any other disease that as per investigator assessment may affect the patient?scompliance or place the patient at higher risk of potential treatmentcomplications