A Study of a Retroviral Replicating Vector Administered to Subjects With Recurrent Malignant Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Tocagen Inc.
Information provided by (Responsible Party):
Tocagen Inc.
ClinicalTrials.gov Identifier:
First received: July 1, 2010
Last updated: June 25, 2015
Last verified: June 2015

July 1, 2010
June 25, 2015
June 2010
July 2016   (final data collection date for primary outcome measure)
Determine the Maximum Feasible, Safe and Well Tolerated Dose of Toca 511 [ Time Frame: 8-10 weeks ] [ Designated as safety issue: Yes ]
Determine the Maximum Tolerated Dose of Toca 511 [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01156584 on ClinicalTrials.gov Archive Site
  • Evaluate the safety and tolerability of repeated treatment with Toca FC following administration of Toca 511 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • Evaluate progression free survival (PFS) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Determine Response Rate at MTD [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Determine the PFS-6 at MTD [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
A Study of a Retroviral Replicating Vector Administered to Subjects With Recurrent Malignant Glioma
A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511 in Patients With Recurrent High Grade Glioma
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.
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.
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Glioblastoma
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligoastrocytoma
  • Biological: Toca 511
    Single, stereotactic, transcranial, intratumoral injection or intravenous injection
    Other Names:
    • Retroviral Replicating Vector (RRV)
    • Gene Therapy
    • Gene Transfer
  • Drug: 5-FC
    4-6 week cycles of Toca FC. Doses evaluated from 120 mg/kg/day or 300 mg/kg/day. Duration of dosing evaluated: 6 days, 7 days or 14 days.
    Other Name: flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)
Experimental: Single arm
Toca 511 vector 5-FC prodrug
  • Biological: Toca 511
  • Drug: 5-FC

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
July 2016
July 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • at least 18 years of age
  • for intratumoral cohorts, supratentorial HGG (WHO grade III or IV)
  • technically unresectable HGG
  • initial definitive therapy such as surgery with or without adjuvant radiation
  • subject elected not to undergo treatment with Gliadel wafer
  • if receiving corticosteroids, dose is stable or decreasing for past 7 days
  • KPS: at least 70
  • absolute neutrophil count > 1500/mm^3
  • absolute lymphocyte count > 500/mm^3
  • platelet count > 100,000/mm^3
  • hemoglobin > 10 g/dL
  • for intratumoral cohort, coagulation profile favorable to surgery
  • estimated glomerular filtration rate > 50 mL/min
  • ALT < 3 times ULN and bilirubin < 1.5 mg/dL
  • negative serum pregnancy test

Exclusion Criteria:

  • cytotoxic therapy within the past 4 weeks (6 weeks for BCNU/CCNU)
  • more than 2 recurrences including present recurrence
  • Gliadel wafer or wafers implanted within the past 8 weeks
  • taking more than 8 mg of dexamethasone per day
  • for intratumoral cohorts, injection of tumor would require violation of ventricular system
  • any infection requiring antibiotic, anticoagulant, or antiplatelet agents within the past 4 weeks
  • for intratumoral cohort, bleeding diathesis or use of anticoagulants/antiplatelet agents that cannot be stopped
  • allergy or intolerance to 5-FC
  • HIV positive
  • g.i. condition that would prevent ingestion or absorption of 5-FC
  • any investigational treatment within the past 30 days
  • pregnant or breast feeding
  • received Avastin
  • history of prior malignancy, excluding basal or squamous cell carcinoma of the skin, with an expected survival of less than 5 years.
18 Years and older
Contact: Asha Das, MD 858-412-8468 adas@tocagen.com
Contact: Mary Rose Keller 858-412-8440 mrkeller@tocagen.com
United States
Tg 511-08-01
Tocagen Inc.
Tocagen Inc.
Not Provided
Not Provided
Tocagen Inc.
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP