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 December 2015 by Tocagen Inc.
Information provided by (Responsible Party):
Tocagen Inc.
ClinicalTrials.gov Identifier:
First received: July 1, 2010
Last updated: February 1, 2016
Last verified: December 2015
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.

Condition Intervention Phase
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Anaplastic Oligoastrocytoma
Biological: Toca 511
Drug: 5-FC
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511 in Patients With Recurrent High Grade Glioma

Resource links provided by NLM:

Further study details as provided by Tocagen Inc.:

Primary Outcome Measures:
  • Determine the Maximum Feasible, Safe and Well Tolerated Dose of Toca 511 [ Time Frame: 8-10 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 70
Study Start Date: June 2010
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm
Toca 511 vector 5-FC prodrug
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)

Detailed Description:
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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01156584

Contact: Asha Das, MD 858-412-8468 adas@tocagen.com
Contact: Mary Lovely 858-412-8473 mlovely@tocagen.com

United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Claudia Aceves, CCRC    626-256-4673 ext 65114    CAceves@coh.org   
Contact: Jana Portnow, MD    626-256-4673 ext 62560    jportnow@coh.org   
Principal Investigator: Jana Portnow, MD         
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Tim Cloughesy, MD    310-825-5321    tcloughesy@mednet.ucla.edu   
Contact: Emy Filka    310-794-3521      
Principal Investigator: Tim Cloughesy, MD         
UCSD Recruiting
San Diego, California, United States, 92093
Contact: Lara Rose    858-822-6575    ljrose@ucsd.edu   
Principal Investigator: David Piccioni, MD         
UCSF Recruiting
San Francisco, California, United States, 94143
Contact: Thelma Munoz    415-353-2523    Munozt@neurosurg.ucsf.edu   
Contact: Manish Aghi, MD       AghiM@neurosurg.ucsf.edu   
Principal Investigator: Manish Aghi, MD         
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: John Gaggin, RN, BSN    313-916-3731    jgaggin1@hfhs.org   
Contact: Stephanie Marl, RN, BS    313-916-7231    smarl1@hfhs.org   
Principal Investigator: Tobias Walbert, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Lori Cappello, RN, BSN    551-996-5098    LCappello@HackensackUMC.org   
Contact: George Kaptain, MD, FACS    551-996-5098    gkaptain@njbsc.com   
Principal Investigator: George Kaptain, MD, FACS         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Cathy Brewer, RN    216-444-7937    BrewerC1@ccf.org   
Contact: Michael Vogelbaum, MD       Vogelbm@ccf.org   
Principal Investigator: Michael Vogelbaum, MD         
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Christopher Rond, MSN, RN    614-293-6563    christopher.rond@osumc.edu   
Contact: James B Elder, MD    614-366-8327    Brad.Elder@osumc.edu   
Principal Investigator: James B Elder, MD         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Melinda Vargas-Jaffe, RN    412-235-1320    vargasjaffema@upmc.edu   
Contact: Kelli S Davis, RN, MSN, OCN    (412) 235-1316    skoviraka@upmc.edu   
Principal Investigator: Johnathan A. Engh, MD         
United States, Texas
The Methodist Hospital Research Institute Recruiting
Houston, Texas, United States, 77030
Contact: Lenis Sosa, MSN, RN    713-441-3245    lsosa@houstonmethodist.org   
Contact: David Baskin, MD    713-441-3800    dbaskin@houstonmethodist.org   
Principal Investigator: David Baskin, MD         
Sponsors and Collaborators
Tocagen Inc.
  More Information

Additional Information:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tocagen Inc.
ClinicalTrials.gov Identifier: NCT01156584     History of Changes
Other Study ID Numbers: Tg 511-08-01 
Study First Received: July 1, 2010
Last Updated: February 1, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Tocagen Inc.:
glioblastoma multiforme
Grade IV astrocytoma
brain cancer
recurrent glioblastoma
anaplastic astrocytoma
anaplastic oligodendroglioma
anaplastic oligoastrocytoma
malignant glioma
high grade glioma

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on February 08, 2016