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

Primary Purpose

Glioblastoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Toca 511 vector
Toca FC
Sponsored by
Tocagen Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring glioma, glioblastoma, glioblastoma multiforme, Grade IV astrocytoma, brain cancer, recurrent glioblastoma, GBM, AA, AOD, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, malignant glioma, high grade glioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • City of Hope
  • UCLA
  • UCSD
  • UCSF
  • Henry Ford Hospital
  • Hackensack University Medical Center
  • Cleveland Clinic Foundation
  • The Ohio State University
  • University of Pittsburgh Medical Center
  • The Methodist Hospital Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

Toca 511 vector/ Toca FC prodrug

Outcomes

Primary Outcome Measures

Maximum Feasible, Safe and Well Tolerated Dose of Toca 511

Secondary Outcome Measures

Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511
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)
Overall survival of Subjects
Evaluate progression free survival (PFS) at 6 months

Full Information

First Posted
July 1, 2010
Last Updated
May 16, 2018
Sponsor
Tocagen Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01156584
Brief Title
A Study of a Retroviral Replicating Vector Combined With a Prodrug Administered to Patients With Recurrent Malignant Glioma
Official Title
A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511 in Patients With Recurrent High Grade Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
July 2010 (undefined)
Primary Completion Date
August 18, 2016 (Actual)
Study Completion Date
August 18, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tocagen Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma
Keywords
glioma, glioblastoma, glioblastoma multiforme, Grade IV astrocytoma, brain cancer, recurrent glioblastoma, GBM, AA, AOD, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, malignant glioma, high grade glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Experimental
Arm Description
Toca 511 vector/ Toca FC prodrug
Intervention Type
Biological
Intervention Name(s)
Toca 511 vector
Other Intervention Name(s)
Retroviral Replicating Vector (RRV), Gene Therapy, Gene Transfer
Intervention Description
Single, stereotactic, transcranial, intratumoral injection or intravenous injection
Intervention Type
Drug
Intervention Name(s)
Toca FC
Other Intervention Name(s)
flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Feasible, Safe and Well Tolerated Dose of Toca 511
Time Frame
8-10 weeks
Secondary Outcome Measure Information:
Title
Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511
Description
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)
Time Frame
6 months
Title
Overall survival of Subjects
Time Frame
Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Title
Evaluate progression free survival (PFS) at 6 months
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asha Das, MD
Organizational Affiliation
Tocagen Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Manish Aghi, MD, NS
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSD
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
The Methodist Hospital Research Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16257382
Citation
Tai CK, Wang WJ, Chen TC, Kasahara N. Single-shot, multicycle suicide gene therapy by replication-competent retrovirus vectors achieves long-term survival benefit in experimental glioma. Mol Ther. 2005 Nov;12(5):842-51. doi: 10.1016/j.ymthe.2005.03.017.
Results Reference
background
PubMed Identifier
22070930
Citation
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.
Results Reference
background
Links:
URL
http://www.abc2.org
Description
Website for Accelerate Brain Cancer Cure
URL
http://www.braintumor.org
Description
Website for the National Brain Tumor Society

Learn more about this trial

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

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