significant toxicity that is directly related to the application 
of our experimental therapy. Such toxicity may include the 
following: 
a. Irreversible diffuse cerebral dysfunction (motor, 
sensory, cognitive) . 
b. Irreversible regional cerebral injury that is not 
related and cannot be explained by the physical 
aspects of the surgical procedures alone. 
c. Permanent Grade 3 toxicity or recurrent Grade 4 
toxicity as specified in Appendix J of the protocol. 
It should be noted that the assessment of 
neurological toxicity (Neurosensory , neuromotor, 
neurocortical , neurocerebellar , neuro-mood, neuro- 
headache, etc. as appears in Appendix J - Toxicity 
Criteria) relates to the relative changes from the 
pre-treatment neurological status. If such toxicity 
is observed in 2 of the first 3 patients, the study 
will be suspended and reevaluated. If no such 
toxicity is observed in the first 3 patients, but 
later is seen, the study will be abandoned. 
d. Other anticipated toxic phenomena that are not 
related directly to the in situ transduction of the 
brain tumor (such as toxicity secondary to GCV 
therapy) , or neurological complications which can 
be explained by the presence of the mass lesion and 
are compatible with the natural history of malignant 
astrocytomas, will not be considered a sufficient 
indication for the termination of the study. Any 
additional occurrence of toxicity will be discussed 
with the Chairman of the IRB. 
e. Upon request of the participating patient or the 
person with the power of attorney the patient may 
withdraw from the study. 
f. A patient will be considered to have failed 
treatment and be taken off the study if any follow- 
up scans shows an increase in the size of tumor 
after treatment. 
III. Data Collection and Monitoring 
A. Study Monitoring. Site visits will be done by GTI to monitor 
the data in the research records and to ensure that all 
regulatory requirements surrounding the study are met. The 
investigator will allow study monitors and the FDA to inspect 
study documents (e.g. consent forms, certificate of analysis, 
case report forms, and pertinent hospital or clinical charts) . 
B. Reporting of Adverse Reactions. (ADRs) to the IND Drug will 
be reported promptly to the FDA, IRB and IBC. ADR reports are 
required even if only a suspicion of a drug effect. 
Previously unknown Grade 2 or 3 reactions will be reported in 
writing within 10 working days. Grade 4 (life-threatening) 
reactions and patient deaths while on treatment will be 
reported by phone within 24 hours. A written report will 
follow within 10 working days 
C. Protocol Amendment Procedures. Any revisions to the original 
protocol will be discussed by all investigators, the FDA and 
others as required. If the consensus is to revise the current 
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