Clinical trial NCT01156584: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Tocagen Inc.
Sponsor class: INDUSTRY
First posted: 2010-07-05
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Maximum Feasible, Safe and Well Tolerated Dose of Toca 511
timeFrame: 8-10 weeks
Secondary outcomes:
measure: Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511
timeFrame: 6 months
measure: Overall survival of Subjects
timeFrame: Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
measure: Evaluate progression free survival (PFS) at 6 months
timeFrame: 6 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Diego
country: United States
facility: UCSD
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
Study officials:
affiliation: Tocagen Inc.
name: Asha Das, MD
role: STUDY_DIRECTOR
affiliation: University of California, San Francisco
name: Manish Aghi, MD, NS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.