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 brain tumors, 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. 
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 
protocol, a formal list of changes will accompany the amended protocol and these will be 
submitted to the FDA, the site’s IRB and other committees. 
D. Publications resulting from Trial. Any manuscript, abstract, or presentation will be 
available to all the study investigators involved in this protocol and the sponsoring company 
for review prior to submission. 
IV. Nature of Procedures or Therapeutic agents (See schema in Appendix F) 
A. Surgical Procedures. A craniotomy will be performed and complete tumor removal will be 
attempted (day 1). The lining of the cavity will then be infiltrated at multiple sites with the 
HS-tk VPC (day 1) to a maximum volume of 5 mL. An Ommaya reservoir, which provides 
an access port to the brain, will be placed into the tumor bed. 
B. Use of the Ommaya Reservoir. Seven days after the initial surgery, the Ommaya reservoir 
will have sealed into the patients brain and surrounding tissues. On day 7 the patient will 
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