Study of a Retroviral Replicating Vector to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor

This study is currently recruiting participants.
Verified July 2012 by Tocagen Inc.
Sponsor:
Information provided by (Responsible Party):
Tocagen Inc.
ClinicalTrials.gov Identifier:
NCT01470794
First received: November 4, 2011
Last updated: November 15, 2013
Last verified: July 2012
  Purpose

This is a multicenter study evaluating the safety and tolerability of Toca 511, a retroviral replicating vector, injected into the resection cavity of patients with recurrent or progressive Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Approximately 6-7 weeks after injection of Toca 511, the patient will take an oral course of 5-FC, an antifungal antibiotic. These courses of 5-FC will be repeated during the 6-month study. MRI scans will be performed approximately every 2 months. Three subjects will be evaluated at up to 5 dose levels of Toca 511. 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.


Condition Intervention Phase
Glioblastoma Multiforme
Anaplastic Astrocytoma
Anaplastic Oligodendroglioma
Anaplastic Oligoastrocytoma
Biological: Toca 511
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 P1 Ascending Dose Trial of Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma & Followed by Treatment With Toca FC, Extended-Release 5-FC

Resource links provided by NLM:


Further study details as provided by Tocagen Inc.:

Primary Outcome Measures:
  • Dose Limiting Toxicities [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Excluding nausea, vomiting 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.


Secondary Outcome Measures:
  • PFS-6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The percentage of subjects who have not progressed or died at 6 months.


Estimated Enrollment: 45
Study Start Date: January 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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. CD converts the antibiotic 5-FC to the anti-cancer drug 5-FU in cells that have been infected by the Toca 511 vector. Beginning approximately 6 weeks after administration of Toca 511, subjects will take a course of oral 5-FC. These courses of 5-FC will be repeated cyclically during the 6-month study.
Other Names:
  • Toca 511, RRV, retroviral replicating vector
  • 5-FC, flucytosine, 5-fluorocytosine, Toca FC

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (must all be answered "Yes"):

  • Has the subject given written informed consent?
  • Is the subject between 18 and 80 years old inclusive?
  • Has the subject undergone at least one prior surgical gross-total or subtotal tumor resection and a course of postoperative radiation therapy with concurrent temozolomide?
  • Does the subject have a single tumor recurrence/progression that is < or = 6 cm in its greatest dimension?
  • Based on pre-operative evaluation, is the tumor recurrence/progression a candidate for a resection of at least 80%?
  • Has the subject elected not to undergo treatment with the Gliadel wafer?
  • Does the subject have a Karnofsky performance status of at least 70%?
  • Does the subjet have an absolute neutrophil count of at least 1500/mm^3?
  • Does the subject have an absolute lymphocyte count of at least 500/mm^3?
  • Does the subject have a platelet count of at least 100,000/mm^3?
  • Does the subject have a Hgb of at least 10 g/dL?
  • Does the subject have a normal PT/PTT?
  • Does the subject have an estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft-Gault formula?
  • Does the subject have an ALT/AST < 3 times the upper limit of the lab reference range and a total bilirubin < 1.5 mg/dL?
  • If the subject is a female of childbearing potential, has she had a negative serum pregnancy test within the past 21 days?
  • For males and females, is the subject willing to use condoms for contraception for 6 months or until vector is no longer detected, whichever is longer?
  • Is the subject willing and able to abide by the protocol?

Exclusion Criteria (must all be answered "No"):

  • Has the subject received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned surgery date?
  • Does the subject have, or has the subject had, within the past 4 weeks an infection requiring antibiotic, antifungal or antiviral therapy?
  • Does the subject have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs, that cannot be stopped for surgery?
  • Does the subject have a history of allergy or intolerance to flucytosine?
  • Is the subject HIV positive?
  • Does the subject have any gastrointestinal disease that would prevent him/her from bing able to ingest or absorb flucytosine?
  • Has the subject received any investigational treatment within the past 30 days?
  • Is the subject breast feeding?
  • Has the subject received Avastin (bevacizumab) for this recurrence/progression, within the past 5 weeks?
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01470794

Contacts
Contact: Daniel Pertschuk, MD 858-412-8409 dpertschuk@tocagen.com
Contact: Tammy Boyce, MEd 858-412-8416 tboyce@tocagen.com

Locations
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Tim Cloughesy, MD    310-825-5321      
Principal Investigator: Tim Cloughesy, MD         
University of California at San Diego Recruiting
San Diego, California, United States, 92093
Contact: Brad Brown    858-822-5377    bdbrown@ucsd.edu   
Contact: Santosh Kesari, MD         
Principal Investigator: Santosh Kesari, 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: Tiffany Pearce    313-916-1784    tpearce1@hfhs.org   
Principal Investigator: Tom Mikkelsen, MD         
United States, New Jersey
JFK Medical Center Recruiting
Edison, New Jersey, United States, 08820
Contact: Charles Porbeni, MD    732-321-7000 ext 68897    cporbeni@jfkhealth.org   
Principal Investigator: Joseph Landolfi, DO         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Cathy Brewer, RN    216-444-7937    brewerc1@ccf.org   
Principal Investigator: Michael Vogelbaum, MD, PhD         
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Jill Brown, MS    614-293-5554    jill.brown@osumc.edu   
Principal Investigator: James Elder, MD         
United States, Washington
Swedish Neuroscience Institute Active, not recruiting
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Tocagen Inc.
  More Information

No publications provided

Responsible Party: Tocagen Inc.
ClinicalTrials.gov Identifier: NCT01470794     History of Changes
Other Study ID Numbers: Tg 511-11-01
Study First Received: November 4, 2011
Last Updated: November 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Tocagen Inc.:
GBM
HGG
High grade glioma
Malignant glioma
Grade III glioma
Grad IV glioma

Additional relevant MeSH terms:
Astrocytoma
Brain Neoplasms
Glioblastoma
Oligodendroglioma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Flucytosine
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014