Recombinant DNA Advisory Committee - 06/7-8/93 
Investigators' Responses-Drs. Raffel and Culver 
Dr. Raffel explained the rationale of proposing this protocol for the treatment of 
pediatric brain tumors. The biology of astrocytoma in children and adults is different, 
e.g., childhood tumors do not possess p53 tumor suppressor gene mutations. Responding 
to Dr. Hirano's question on the "stop/proceed" criterion. Dr. Raffel said that tumor 
recurrence occurs quickly without additional therapy. A failure will be considered tumor 
recurrence within 3 months of vector producing cell (VPC) administration. Patient with 
recurrent tumors will not be eligible for retreatment. Otherwise, additional rounds of 3 
treatment cycles will continue. Regarding the issue of an assent form for children. Dr. 
Raffel agreed to make changes as permitted by his IRB. As to the animal studies, 
results were obtained in young rats, which may not be comparable to 2 year old humans. 
This study excludes patients below 2 years of age because their brain development is 
incomplete. 
Responding to a question by Dr. Miller about differences between the proposed vector 
and the vector used in the 2 previously approved human trials, Dr. Culver stated that the 
vector and the VPC proposed for this study are the same vector used for other studies. 
Several vectors were compared in animal studies. Regarding the toxicity issue of the two 
ongoing brain tumor trials, Dr. Culver stated that no acute toxicity was encountered, but 
a chronic or subacute adverse reaction was reported by Dr. Oldfield. Dr. Culver stated 
that in this protocol, attempts will be made to select patients with rapidly growing tumors 
and to remove as much necrosis as possible from the tumor mass to allow for optimal 
"bystander" effects of the VPC on surrounding tumor cells. 
In response to Dr. Hirano's question about the statistics of the stopping rule, Dr. Raffel 
said that statistical analysis indicates that if 15 patients are treated and no responses are 
observed, the chance of missing an effective treatment is less than 5%. This outcome is 
the cut off point. If a response is observed, then a total of 30 patients will be treated. 
A lengthy discussion ensued regarding the necessity for obtaining proper assent from 
children. The suggestion was made that there are children's assent forms for other 
protocols that could be used as an example, e.g., the assent form for the ADA protocol. 
Committee Motion 
A motion was made by Dr. Hirano and seconded by Dr. Geiduschek to approve the 
protocol. An amendment was made by Dr. Zallen and seconded by Ms. Meyers that the 
investigators will submit an assent document that will inform children of the 
experimental procedures and associated risks. This document must be reviewed and 
approved by Drs. Zallen and Secundy. The motion to approve the amendment passed by 
a vote of 19 in favor, 0 opposed, and 2 abstentions. The motion to approve the protocol 
Recombinant DNA Research, Volume 17 
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