NCT01985256

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Feb 2014

Typical duration for phase_1

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 8, 2013

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 15, 2013

Completed
3 months until next milestone

Study Start

First participant enrolled

February 1, 2014

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 3, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 3, 2016

Completed
Last Updated

May 21, 2018

Status Verified

May 1, 2018

Enrollment Period

2.1 years

First QC Date

November 8, 2013

Last Update Submit

May 16, 2018

Conditions

Glioblastoma MultiformeAnaplastic AstrocytomaAnaplastic OligodendrogliomaAnaplastic Oligoastrocytoma

Keywords

gliomaglioblastomaglioblastoma multiformeGrade IV astrocytomabrain cancerrecurrent glioblastomaGBMAAAODanaplastic astrocytomaanaplastic oligodendrogliomaanaplastic oligoastrocytomamalignant gliomahigh grade glioma

Outcome Measures

Primary Outcomes (1)

  • Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities.

    32 weeks

Secondary Outcomes (5)

  • Measure Toca 511 deposition in tumor at the time of resection by QT-PCR

    At time of surgical resection

  • Measure how long Toca 511 stays in blood after IV administration by serum QT-PCR

    10 days

  • Safety and tolerability of Toca FC given at various doses and schedules as measured by dose limiting toxicities.

    32 weeks

  • Evaluate preliminary efficacy of Toca 511 and Toca FC by assessing overall survival, and tumor response rates.

    Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12)

  • Evaluate preliminary efficacy by assessing landmark PFS [6 months]

    6 months

Study Arms (1)

Single Arm

EXPERIMENTAL

Toca 511 vector/Toca FC

Biological: Toca 511Drug: Toca FC

Interventions

Toca 511BIOLOGICAL

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.

Also known as: vocimagene amiretrorepvec, retroviral replicating vector (RRV)
Single Arm
Toca FCDRUG
Also known as: flucytosine, 5-FC, 5-FC XR, Toca FC
Single Arm

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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?
  • +3 more criteria

You may not qualify if:

  • 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?

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

UC Irivine

Irvine, California, 92868, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

UC San Diego, Moores Cancer Center

San Diego, California, 92093, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

JFK Medical Center New Jersery

Edison, New Jersey, 08818, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

  • Ostertag D, Amundson KK, Lopez Espinoza F, Martin B, Buckley T, Galvao da Silva AP, Lin AH, Valenta DT, Perez OD, Ibanez CE, Chen CI, Pettersson PL, Burnett R, Daublebsky V, Hlavaty J, Gunzburg W, Kasahara N, Gruber HE, Jolly DJ, Robbins JM. Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. Neuro Oncol. 2012 Feb;14(2):145-59. doi: 10.1093/neuonc/nor199. Epub 2011 Nov 9.

    PMID: 22070930BACKGROUND

MeSH Terms

Conditions

GlioblastomaAstrocytomaOligodendrogliomaGliomaBrain Neoplasms

Interventions

vocimagene amiretrorepvecFlucytosine

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

CytosinePyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Asha Das, MD

    Tocagen Inc.

    STUDY DIRECTOR

  • Steven Kalkanis, MD

    Henry Ford Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 8, 2013

First Posted

November 15, 2013

Study Start

February 1, 2014

Primary Completion

March 3, 2016

Study Completion

March 3, 2016

Last Updated

May 21, 2018

Record last verified: 2018-05

Locations

US(6)