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

Sponsor

Tocagen Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01156584

Collaborator

(none)

Enrollment

Locations

Arm

73.6

Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

N/A

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 :

Jul 1, 2010

Actual Primary Completion Date :

Aug 18, 2016

Actual Study Completion Date :

Aug 18, 2016

Arms and Interventions

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

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 Names:

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

Outcome Measures

Primary Outcome Measures

Maximum Feasible, Safe and Well Tolerated Dose of Toca 511 [8-10 weeks]

Secondary Outcome Measures

Safety and tolerability of repeated treatment with Toca FC following administration of Toca 511 [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 [Overall survivial, Overall survivial at 6 months (OS6), 9 months (OS9), and 12 months (OS12)]
Evaluate progression free survival (PFS) at 6 months [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	UCLA	Los Angeles	California	United States	90095
3	UCSD	San Diego	California	United States	92093
4	UCSF	San Francisco	California	United States	94143
5	Henry Ford Hospital	Detroit	Michigan	United States	48202
6	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
7	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
8	The Ohio State University	Columbus	Ohio	United States	43210
9	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
10	The Methodist Hospital Research Institute	Houston	Texas	United States	77030