The Toca 5 Trial: Toca 511 & Toca FC Versus Standard of Care in Patients With Recurrent High Grade Glioma

Exclusion Criteria

• •1. History of more than 2 prior recurrences (including this recurrence) of GBM or AA
• •2. 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
• •3. Histologically confirmed oligodendroglioma or mixed glioma
• •4. Known 1p/19q co deletion
• •5. 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; or
• •* \> 5 cm in any dimension
• •6. The subject has or had any active infection requiring systemic antibiotic, antifungal or antiviral therapy within the past 4 weeks
• •7. The subject 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
• •8. The subject is human immunodeficiency virus (HIV) positive
• •9. The subject has a history of allergy or intolerance to flucytosine
• •10. The subject has a gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine
• •11. The subject received cytotoxic chemotherapy within the past 4 weeks (6 weeks for nitrosoureas) of the planned surgery date
• •12. The subject received any investigational treatment within the past 30 days or prior immunotherapy or antibody therapy within the past 45 days.
• •13. The subject is pregnant or breast feeding
• •14. The subject 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)
• •15. The subject has received bevacizumab for their disease unless in the context of primary therapy for newly diagnosed glioma
• •16. For subjects planned to potentially receive bevacizumab, they have 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
• •17. The subject has received systemic dexamethasone continuously at a dose \> 8 mg/day for 8 weeks prior to the date of the screening assessment
• •18. 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)
• •* Subjects who have any other disease, either metabolic or psychological, which as per Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications