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

May 16, 2018 updated by: Tocagen Inc.

A Phase 1 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

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 patients 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, patients will begin an oral courses of Toca FC, an antifungal agent. These one week courses of Toca FC will be repeated during the approximately 30 week study. Two separate cohorts of patients treated with Toca 511 and Toca FC will also be evaluated with either of the following standard treatments for glioma: lomustine or bevacizumab. After completion of this study, all patients will be eligible for enrollment and encouraged to enter 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA
      • San Diego, California, United States, 92093
        • University of California at San Diego
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • New Jersey
      • Edison, New Jersey, United States, 08820
        • JFK Medical Center
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Neuroscience Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

  • Has the patient given written informed consent?
  • Is the patient between 18 years old and 80 years old inclusive?
  • Has the patient 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 patient 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 patient elected not to undergo treatment with the Gliadel® wafer?
  • Does the patient have a Karnofsky performance status ≥ 70?
  • Does the patient have an absolute neutrophil count (ANC) ≥ 1500/mm3?
  • Does the patient have an absolute lymphocyte count ≥ 500/mm3?
  • Does the patient have a platelet count ≥ 100,000/mm3?
  • Does the patient have a Hgb ≥ 10 g/dL?
  • Does the patient have a normal PT/PTT? (subnormal PT/PTT acceptable)
  • Does the patient have an estimated glomerular filtration rate of at least 50 mL/min (inclusive) by the Cockcroft-Gault formula?
  • Does the patient have an ALT < 3 times the upper limit of the laboratory reference range and total bilirubin < 1.5 mg/dL?
  • If the patient is a female of childbearing potential, has she had a negative serum pregnancy test within the past 21 days?
  • Is the patient 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 patient is a fertile female, is she willing to use contraception for at least 12 months?
  • Is the patient willing and able to abide by the protocol?

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

  • Has the patient received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned surgery date?
  • Does the patient have, or has the subject had, within the past 4 weeks any infection requiring antibiotic, antifungal or antiviral therapy?
  • Has the patient had a surgical procedure in the last 28 days or a surgical wound that is not healed?
  • Does the patient have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery?
  • Does the patient have a history of allergy or intolerance to flucytosine?
  • Is the patient HIV positive?
  • Does the patient have any gastrointestinal disease that would prevent him or her from being able to ingest or absorb flucytosine?
  • Has the patient received any investigational treatment within the past 30 days?
  • Is the patient breast feeding?
  • Has the patient 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?

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm
Toca 511 vector/Toca FC prodrug
Biological: Toca 511 vector
All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene. CD converts the antifungal 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, patients will begin courses of oral Toca FC at pre-specified intervals, depending on cohort, during the approximately 30 week study.
Other Names:
  • Toca 511, RRV, retroviral replicating vector
  • 5-FC, flucytosine, 5-fluorocytosine, Toca FC
Drug: Toca FC
Other Names:
  • flucytosine, 5-FC, 5-FC XR, Toca FC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicities
Time Frame: 2 months
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/Toca FC combination.
2 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival of Subjects
Time Frame: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Progression Free Survival (PFS) of Subjects
Time Frame: PFS of subjects at 6 months (PFS-6)
PFS of subjects at 6 months (PFS-6)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tocagen Inc.

Investigators

  • Principal Investigator: Timothy Cloughesy, MD, NO, University of California, Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2012

Primary Completion (Actual)

April 12, 2016

Study Completion (Actual)

April 12, 2016

Study Registration Dates

First Submitted

November 4, 2011

First Submitted That Met QC Criteria

November 9, 2011

First Posted (Estimate)

November 11, 2011

Study Record Updates

Last Update Posted (Actual)

May 21, 2018

Last Update Submitted That Met QC Criteria

May 16, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Tg 511-11-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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