A P1 Ascending Dose Trial of the Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma and Followed by Treatment With Toca FC, Extended-Release 5-FC
Inclusion Criteria (must all be answered "Yes"):
- Has the subject given written informed consent?
- Is the subject between 18 and 80 years old inclusive?
- Has the subject undergone at least one prior surgical gross-total or subtotal tumor
resection and a course of postoperative radiation therapy with concurrent
- Does the subject have a single tumor recurrence/progression that is < or = 6 cm in
its greatest dimension?
- Based on pre-operative evaluation, is the tumor recurrence/progression a candidate
for a resection of at least 80%?
- Has the subject elected not to undergo treatment with the Gliadel wafer?
- Does the subject have a Karnofsky performance status of at least 70%?
- Does the subjet have an absolute neutrophil count of at least 1500/mm^3?
- Does the subject have an absolute lymphocyte count of at least 500/mm^3?
- Does the subject have a platelet count of at least 100,000/mm^3?
- Does the subject have a Hgb of at least 10 g/dL?
- Does the subject have a normal PT/PTT?
- Does the subject have an estimated glomerular filtration rate of at least 50 mL/min
by the Cockcroft-Gault formula?
- Does the subject have an ALT/AST < 3 times the upper limit of the lab reference range
and a total bilirubin < 1.5 mg/dL?
- If the subject is a female of childbearing potential, has she had a negative serum
pregnancy test within the past 21 days?
- For males and females, is the subject willing to use condoms for contraception for 6
months or until vector is no longer detected, whichever is longer?
- Is the subject willing and able to abide by the protocol?
Exclusion Criteria (must all be answered "No"):
- Has the subject received cytotoxic chemotherapy within the past 3 weeks (6 weeks for
nitrosoureas) of the planned surgery date?
- Does the subject have, or has the subject had, within the past 4 weeks an infection
requiring antibiotic, antifungal or antiviral therapy?
- Does the subject have any bleeding diathesis, or must the subject take any
anticoagulants, or antiplatelet agents, including NSAIDs, that cannot be stopped for
- Does the subject have a history of allergy or intolerance to flucytosine?
- Is the subject HIV positive?
- Does the subject have any gastrointestinal disease that would prevent him/her from
bing able to ingest or absorb flucytosine?
- Has the subject received any investigational treatment within the past 30 days?
- Is the subject breast feeding?
- Has the subject received Avastin (bevacizumab) for this recurrence/progression,
within the past 5 weeks?