ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01156584
Recruitment Status : Completed
First Posted : July 5, 2010
Last Update Posted : May 21, 2018
Sponsor:
Information provided by (Responsible Party):
Tocagen Inc.

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.

Condition or disease Intervention/treatment Phase
Glioblastoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma Biological: Toca 511 vector Drug: Toca FC Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Ascending Dose Trial of the Safety and Tolerability of Toca 511 in Patients With Recurrent High Grade Glioma
Study Start Date : July 2010
Actual Primary Completion Date : August 18, 2016
Actual Study Completion Date : August 18, 2016


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:
  • Retroviral Replicating Vector (RRV)
  • Gene Therapy
  • 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 Name: flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)



Primary Outcome Measures :
  1. Maximum Feasible, Safe and Well Tolerated Dose of Toca 511 [ Time Frame: 8-10 weeks ]

Secondary Outcome Measures :
  1. 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)

  2. Overall survival of Subjects [ Time Frame: Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12) ]
  3. Evaluate progression free survival (PFS) at 6 months [ Time Frame: 6 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01156584


Locations
United States, California
City of Hope
Duarte, California, United States, 91010
UCLA
Los Angeles, California, United States, 90095
UCSD
San Diego, California, United States, 92093
UCSF
San Francisco, California, United States, 94143
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
The Methodist Hospital Research Institute
Houston, Texas, United States, 77030
Sponsors and Collaborators
Tocagen Inc.
Investigators
Study Director: Asha Das, MD Tocagen Inc.
Principal Investigator: Manish Aghi, MD, NS University of California, San Francisco

Additional Information:
Publications:
Responsible Party: Tocagen Inc.
ClinicalTrials.gov Identifier: NCT01156584     History of Changes
Other Study ID Numbers: Tg 511-08-01
First Posted: July 5, 2010    Key Record Dates
Last Update Posted: May 21, 2018
Last Verified: May 2018

Keywords provided by Tocagen Inc.:
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

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Flucytosine
Antifungal Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action