This is a multicenter study evaluating the safety and tolerability of Toca 511 administered intravenously to patients with recurrent or progressive Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Patients meeting all of the inclusion and none of the exclusion criteria will receive an initial dose of Toca 511 administered as an intravenous, bolus injection, followed approximately 11 days later by an additional dose injected into the walls of the resection cavity at the time of planned tumor resection. Approximately 6 weeks later, patients will begin treatment with oral Toca FC, an antifungal agent, and repeated every 4 weeks. All patients enrolled in this study will be encouraged to participate in a continuation protocol that enables additional Toca FC administration and the collection of long-term safety and response data.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene, intravenously and then intracranially. CD converts the antifungal 5-fluorocytosine (5-FC) to the anti-cancer drug 5-fluorouracil (5-FU) in cells that have been infected by the Toca 511 vector. Beginning approximately 6 weeks after the second administration of Toca 511,patients will begin 7-day course of oral 5-FC, repeated every 4 weeks for the duration of the study.
UC Irivine
Irvine, California, United States
UCLA
Los Angeles, California, United States
UC San Diego, Moores Cancer Center
San Diego, California, United States
Henry Ford Hospital
Detroit, Michigan, United States
JFK Medical Center New Jersery
Edison, New Jersey, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities.
Time frame: 32 weeks
Measure Toca 511 deposition in tumor at the time of resection by QT-PCR
Time frame: At time of surgical resection
Measure how long Toca 511 stays in blood after IV administration by serum QT-PCR
Time frame: 10 days
Safety and tolerability of Toca FC given at various doses and schedules as measured by dose limiting toxicities.
Time frame: 32 weeks
Evaluate preliminary efficacy of Toca 511 and Toca FC by assessing overall survival, and tumor response rates.
Time frame: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Evaluate preliminary efficacy by assessing landmark PFS [6 months]
Time frame: 6 months
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