Study of a Retroviral Replicating Vector Given Intravenously to Patients Undergoing Surgery for Recurrent Brain Tumor

May 16, 2018 updated by: Tocagen Inc.

A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered Intravenously Prior to, and Intracranially at the Time of, Subsequent Resection for Recurrent HGG & Followed by Treatment With Extended-Release 5-FC

This is a multicenter study evaluating the safety and tolerability of Toca 511 administered intravenously to patients with recurrent or progressive Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Patients meeting all of the inclusion and none of the exclusion criteria will receive an initial dose of Toca 511 administered as an intravenous, bolus injection, followed approximately 11 days later by an additional dose injected into the walls of the resection cavity at the time of planned tumor resection. Approximately 6 weeks later, patients will begin treatment with oral Toca FC, an antifungal agent, and repeated every 4 weeks. All patients enrolled in this study will be encouraged to participate in a continuation protocol that enables additional Toca FC administration and the collection of long-term safety and response data.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
17

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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
      • Irvine, California, United States, 92868
        • UC Irivine
      • Los Angeles, California, United States, 90095
        • UCLA
      • San Diego, California, United States, 92093
        • UC San Diego, Moores Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • New Jersey
      • Edison, New Jersey, United States, 08818
        • JFK Medical Center New Jersery
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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 HGG 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 either (1) a single, enhancing tumor recurrence/progression that is ≤ 8 cm in greatest dimension, or (2) multiple enhancing tumor recurrences/progressions within the same surgical field where the sum of their greatest dimensions is ≤ 8 cm?
  • 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 coagulation profile that would allow for the safe performance of surgery under general anesthesia?
  • 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?
  • Does the subject have adequate venous access?

Exclusion Criteria:

  • Has the subject received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned date of vector injection?
  • 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 received Avastin® (bevacizumab) for this recurrence/progression, or within the 4 weeks prior to planned Visit 1?
  • 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 swallow or absorb flucytosine?
  • Has the subject received any investigational treatment within the past 30 days?
  • Is the subject breastfeeding?
  • 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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Single Arm
Toca 511 vector/Toca FC
Drug: Toca FC
Other Names:
  • flucytosine, 5-FC, 5-FC XR, Toca FC
Biological: Toca 511
All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene, intravenously and then intracranially. CD converts the antifungal 5-fluorocytosine (5-FC) to the anti-cancer drug 5-fluorouracil (5-FU) in cells that have been infected by the Toca 511 vector. Beginning approximately 6 weeks after the second administration of Toca 511,patients will begin 7-day course of oral 5-FC, repeated every 4 weeks for the duration of the study.
Other Names:
  • vocimagene amiretrorepvec
  • retroviral replicating vector (RRV)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities.
Time Frame: 32 weeks
32 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Measure Toca 511 deposition in tumor at the time of resection by QT-PCR
Time Frame: At time of surgical resection
At time of surgical resection
Measure how long Toca 511 stays in blood after IV administration by serum QT-PCR
Time Frame: 10 days
10 days
Safety and tolerability of Toca FC given at various doses and schedules as measured by dose limiting toxicities.
Time Frame: 32 weeks
32 weeks
Evaluate preliminary efficacy of Toca 511 and Toca FC by assessing overall survival, and tumor response rates.
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)
Evaluate preliminary efficacy by assessing landmark PFS [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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tocagen Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Steven Kalkanis, MD, Henry Ford Hospital

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 3, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 3, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 8, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 15, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 21, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Tg 511-13-01

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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