Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Tocagen Inc.
Sponsor:
Information provided by (Responsible Party):
Tocagen Inc.
ClinicalTrials.gov Identifier:
NCT01470794
First received: November 4, 2011
Last updated: February 18, 2015
Last verified: February 2015
  Purpose

This is a multicenter study evaluating the safety and tolerability of increasing doses of Toca 511, a retroviral replicating vector, injected into the resection cavity of subjects with Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Approximately 6 weeks after injection of Toca 511, subjects will take an oral course of 5-FC, an antifungal antibiotic. These one week courses of 5-FC will be repeated during the 29 week study. In some subjects, Toca 511 and Toca FC will also be evaluated with either of the following standard treatments for glioma: lomustine, a drug approved by the FDA to treat brain tumors or bevacizumab, an alternative drug approved by the FDA to treat brain tumors. After completion of this study, all subjects will be eligible for enrollment and encouraged to be in a long-term continuation protocol that enables additional Toca FC treatment cycles to be given, as well as permits the collection of long-term safety and survival 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:
  • Overall Survival of Subjects [ Time Frame: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12) ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: January 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: October 2015 (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 years old and 80 years old inclusive?
  • Has the subject had histologically proven HGG with recurrence or progression following initial definitive therapy(s) such as surgery with or without adjuvant radiation therapy and/or chemotherapy (confirmed by diagnostic biopsy or contrast-enhanced MRI and evaluable by Macdonald criteria)? Note if first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field.
  • Does the subject have a single, HGG tumor recurrence/progression that is ≤ 5 cm in its greatest dimension?
  • Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate for ≥ 80% resection?
  • Has the subject elected not to undergo treatment with the Gliadel® wafer?
  • Does the subject have a Karnofsky performance status ≥ 70?
  • Does the subject have an absolute neutrophil count (ANC) ≥ 1500/mm3?
  • Does the subject have an absolute lymphocyte count ≥ 500/mm3?
  • Does the subject have a platelet count ≥ 100,000/mm3?
  • Does the subject have a Hgb ≥ 10 g/dL?
  • Does the subject have a normal PT/PTT? (subnormal PT/PTT acceptable)
  • Does the subject have an estimated glomerular filtration rate of at least 50 mL/min (inclusive) by the Cockcroft-Gault formula?
  • Does the subject have an ALT < 3 times the upper limit of the laboratory reference range and 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?
  • Is the subject willing to use condoms for contraception for 6 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer. If the subject is a fertile female, is she willing to use contraception for at least 12 months?
  • 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 any infection requiring antibiotic, antifungal or antiviral therapy?
  • Has the subject had a surgical procedure in the last 28 days or a surgical wound that is not healed?
  • 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 or her from being 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, or within the past 5 weeks?
  • Does the patient have a history of prior malignancy, excluding basal or squamous cell carcinoma of the skin, with an expected survival of less than five 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: NCT01470794

Contacts
Contact: Wayne Saville, MD 858-412-8440 wsaville@tocagen.com
Contact: Mary Rose Keller 858-412-8499 mrkeller@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: February 18, 2015
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
Glioblastoma
Gliosarcoma
Oligodendroglioma
Glioma
Neoplasms
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 March 01, 2015