Clinical Trial: A Study of a Retroviral Replicating Vector Administered to Subjects With Recurrent Malignant Glioma
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511 in Patients With Recurrent High Grade Glioma
Brief Summary: This is a multicenter, open-label, ascending-dose trial of the safety and tolerability of increasing doses of Toca 511, a Retroviral Replicating Vector (RRV), administered to subjects with recurrent high grade glioma (rHGG) who have undergone surgery followed by adjuvant radiation therapy and chemotherapy. Subjects will recieve Toca 511 via stereotactic, transcranial injection into their tumor. Cohort 7 & 9 will receive Toca 511 as an intravenous injection given daily for 3 & 5 days respectively. Approximately 3-4 weeks following injection of the RRV, treatment with Toca FC will commence and will be repeated approximately every 6 weeks until study completion or enrollment in the continuation study.
Detailed Summary: There is an ongoing, intensive search for novel therapies to improve the prognosis of patients with the most common and aggressive form of primary brain cancer, glioblastoma multiforme (GBM). Gene transfer is one such approach. Early gene-transfer studies with replication incompetent vectors showed this approach to be generally safe, but ineffective due to limited transduction of the tumor. More recently gene transfer has been attempted with oncolytic, replicating viruses. However these viruses are rapidly cleared by the immune system. To overcome these shortcomings of previous gene transfer protocols, Toca 511 has been developed utilizing a Retroviral Replicating Vector (RRV). This platform has the following potential advantages: 1) The vector only infects dividing cells, 2) The virus stably integrates into the genome of the tumor cells allowing for the potential for long-term control of the tumor, 3) The virus is not intrinsically oncolytic and is not cleared from the tumor by the immune system, and 4) The virus has been engineered to express the prodrug-activator, cytosine deaminase (CD), a gene that catalyzes the intracellular conversion of the antifungal drug, 5-FC (flucytosine) to the cytotoxic drug 5-FU. In both xenograft and syngeneic intracranial mouse tumor models the Toca 511/5-FC combination was able to significantly increase the survival of treated animals. The goal of the current trial is to demonstrate the safety and efficacy of Toca 511 administered intratumorally to patients with recurrent GBM followed by cyclic treatment with the prodrug 5-FC.
Sponsor: Tocagen Inc.
Current Primary Outcome: Determine the Maximum Feasible, Safe and Well Tolerated Dose of Toca 511 [ Time Frame: 8-10 weeks ]
Original Primary Outcome: Determine the Maximum Tolerated Dose of Toca 511 [ Time Frame: 7 weeks ]
Current Secondary Outcome:
- Evaluate the safety and tolerability of repeated treatment with Toca FC following administration of Toca 511 [ Time Frame: 6 months ]Review of adverse events including laboratory safety data (specifically 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/Toca FC combination)
- Evaluate overall survival at 6, 9 and 12 months [ Time Frame: 12 months ]
- Evaluate progression free survival (PFS) at 6 months [ Time Frame: 6 months ]
Original Secondary Outcome:
- Determine Response Rate at MTD [ Time Frame: 6 months ]
- Determine the PFS-6 at MTD [ Time Frame: 6 months ]
Information By: Tocagen Inc.
Dates:
Date Received: July 1, 2010
Date Started: June 2010
Date Completion: July 2017
Last Updated: November 11, 2016
Last Verified: November 2016
