A Study of a Retroviral Replicating Vector Combined With a Prodrug Administered to Patients With Recurrent Malignant Glioma

May 16, 2018 updated by: Tocagen Inc.

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 patients with recurrent high grade glioma (rHGG) who have undergone surgery followed by adjuvant radiation therapy and chemotherapy. Patients will receive Toca 511 either via stereotactic, transcranial injection into their tumor or as an intravenous injection given daily for 3 & 5 days, depending on cohort. Approximately 3-4 weeks following injection of the RRV, treatment with Toca FC, an antifungal agent, will commence and will be repeated approximately every 6 weeks until study completion. 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)

54

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
      • Duarte, California, United States, 91010
        • City of Hope
      • Los Angeles, California, United States, 90095
        • UCLA
      • San Diego, California, United States, 92093
        • UCSD
      • San Francisco, California, United States, 94143
        • UCSF
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital Research 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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Single arm
Toca 511 vector/ Toca FC prodrug
Biological: Toca 511 vector
Single, stereotactic, transcranial, intratumoral injection or intravenous injection
Other Names:
  • Gene Therapy
  • Retroviral Replicating Vector (RRV)
  • Gene Transfer
Drug: Toca 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 Names:
  • flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Feasible, Safe and Well Tolerated Dose of Toca 511
Time Frame: 8-10 weeks
8-10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511
Time Frame: 6 months
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)
6 months
Overall survival of Subjects
Time Frame: Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Evaluate progression free survival (PFS) at 6 months
Time Frame: 6 months
6 months

Collaborators and Investigators

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

Sponsor

Tocagen Inc.

Investigators

  • Principal Investigator: Manish Aghi, MD, NS, University of California, San Francisco

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

Helpful Links

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

July 1, 2010

Primary Completion (ACTUAL)

August 18, 2016

Study Completion (ACTUAL)

August 18, 2016

Study Registration Dates

First Submitted

July 1, 2010

First Submitted That Met QC Criteria

July 2, 2010

First Posted (ESTIMATE)

July 5, 2010

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 511-08-01

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.

Clinical Trials on Glioblastoma

Clinical Trials on Toca 511 vector

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Venezuela

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe