Trial | NCT01156584  Report issue

Title

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

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    54
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.
Study Started
Jul 31
2010
Primary Completion
Aug 18
2016
Study Completion
Aug 18
2016
Last Update
May 21
2018

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 names: flucytosine, 5-FC, 5-FC XR, Toca FC (extended release flucytosine)

Single arm Experimental

Toca 511 vector/ Toca FC prodrug

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.
No Results Posted