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

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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.

July 1, 2010
July 5, 2010
May 21, 2018
July 2010
August 18, 2016   (Final data collection date for primary outcome measure)
Maximum Feasible, Safe and Well Tolerated Dose of Toca 511 [ Time Frame: 8-10 weeks ]
Determine the Maximum Tolerated Dose of Toca 511 [ Time Frame: 7 weeks ]
Complete list of historical versions of study NCT01156584 on ClinicalTrials.gov Archive Site
  • 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)
  • Overall survival of Subjects [ Time Frame: 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 ]
  • Determine Response Rate at MTD [ Time Frame: 6 months ]
  • Determine the PFS-6 at MTD [ Time Frame: 6 months ]
Not Provided
Not Provided
 
A Study of a Retroviral Replicating Vector Combined With a Prodrug Administered to Patients With Recurrent Malignant Glioma
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.
Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Glioblastoma
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligoastrocytoma
  • 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)
Experimental: Single arm
Toca 511 vector/ Toca FC prodrug
Interventions:
  • Biological: Toca 511 vector
  • Drug: Toca FC

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
54
24
August 18, 2016
August 18, 2016   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01156584
Tg 511-08-01
Yes
Not Provided
Not Provided
Tocagen Inc.
Tocagen Inc.
Not Provided
Study Director: Asha Das, MD Tocagen Inc.
Principal Investigator: Manish Aghi, MD, NS University of California, San Francisco
Tocagen Inc.
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP