Study of a Retroviral Replicating Vector Given Intravenously to Patients Undergoing Surgery for Recurrent Brain Tumor
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 will receive ½ of the Toca 511 intravenously, followed approximately 11 days later by removal of the tumor and injection of the remaining ½ of the Toca 511 into the resection cavity. The tumor specimen will be tested for the presence of Toca 511. Approximately 4 weeks later, the patient will take an oral 10-day course of Toca FC, an antifungal antibiotic. These 10-day courses of Toca FC will be repeated approximately every 5 weeks until study completion. MRI scans will be performed approximately every 2 months. One subject each will be evaluated at 3 dose levels of Toca 511. Three subjects each will be evaluated in the 4th and 5th dosing cohorts. These cohorts will evaluate multiday intravenous administration of Toca 511: 3 consecutive days for the 4th cohort and 5 consecutive days for the 5th cohort. The dose of Toca 511 a patient receives will depend upon the number of previous study participants and how well they have tolerated the study drugs. All patients enrolled in this study will be encouraged to participate in a continuation protocol that enables additional 5-FC administration and the collection of long-term safety and response data.
Biological: Toca 511
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A P1 Ascending Dose Trial of the Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered Intravenously Prior to, and Intracranially at the Time of, Subsequent Resection for Recurrent HGG & Followed by Treatment With Extended-Release 5-FC|
- Dose Limiting Toxicities [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]Excluding nausea, vomiting, weakness, and fatigue, any Grade 3 or higher non-hematologic toxicity or any Grade 4 or higher hematologic toxicity, felt to be related to Toca 511 or the Toca 511/5-FC combination.
- PFS-6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]The percentage of subjects who have not progressed or died at 6 months.
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Toca 511 vector
Toca 511 a retroviral replicating vector expressing the cytosine deaminase enzyme
Biological: Toca 511
All subjects will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene, intravenously and then intracranially. CD converts the antibiotic 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 4 weeks after second administration of Toca 511, subjects will take an 10-day course of oral 5-FC. These 10-day courses of 5-FC are repeated every 5 weeks for the duration of the study.
|Contact: Daniel Pertschuk, MDemail@example.com|
|Contact: Tammy Boyce, MEdfirstname.lastname@example.org|
|United States, Michigan|
|Henry Ford Hospital||Recruiting|
|Detroit, Michigan, United States, 48202|
|Contact: John Gaggin, RN, BSN 313-916-3731 email@example.com|
|Contact: Tiffany Pearce 313-916-1784 firstname.lastname@example.org|
|Principal Investigator: Steven N Kalkanis, MD|