A Continuation Protocol for Patients Previously Enrolled in a Study of Toca 511

Study Overview
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Brief Summary
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This is a multicenter, open-label, continuation study to allow subjects who have previously received Toca 511 to continue to receive Toca FC and to allow for extended safety observations. Subjects will be seen on an every six week basis for 1 year or longer. Subjects who continue to receive Toca FC will receive the dose described in the parent protocol. If the Toca FC dose is adjusted for any reason, the serum concentration will be monitored. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scans will be performed as per standard of care. If the subject has recurred/progressed, repeat intracranial injection of Toca 511 followed by Toca FC treatment may be offered to consenting patients. Subjects who enter the study to continue Toca FC and subsequently discontinue Toca FC, and subjects who are only willing or able to perform limited testing will have viral testing alone, at the appropriate intervals. After the first year, subjects will be seen twice yearly for the next 4 years and then contacted yearly for the next 10 years. All subjects will be followed on study for at least 5 years regardless of whether they are taking Toca FC.

Official Title
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A Continuation Protocol for Patients Previously Enrolled in a Study of Toca 511

Conditions
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Glioblastoma Multiforme, Astrocytoma, Gliomas, Malignant

Intervention / Treatment
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* Biological: Toca 511 vector
* Drug: Toca FC • Flucytosine • 5-FC • 5-Fluorocytosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent Form Subject received Toca 511 in prior study. Subject is willing to abide by protocol Exclusion Criteria: Subject has history of allergy or intolerance to flucytosine

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Single arm Toca 511 vector/5-FC prodrug | Biological: Toca 511 vector<br>* Toca 511 consists of a purified retroviral replicating vector encoding a modified yeast cytosine deaminase (CD) gene. The CD gene converts the antifungal 5-flurocytosine (5FC) to the anticancer drug 5-FU in cells that have been infected by the Toca 511 vector<br>* Other names: retroviral replicating virus;Drug: Toca FC • Flucytosine • 5-FC • 5-Fluorocytosine<br>* Toca FC is an extended-release formulation of flucytosine.<br>* Other names: 5-Fluorocytosine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term safety follow up | This will be based on treatment emergent adverse events, clinical laboratory values and viral testing. | From study entry up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival in days from the initial Toca 511 administration on parent study to the date of death. |  | From initial Toca 511 administration to death of last patient alive for up to 15 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioma, glioblastoma, glioblastoma multiforme, Grade IV astrocytoma, brain cancer, recurrent glioblastoma, GBM, AA, AOD, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, high grade glioma