Recombinant DMA Advisory Committee- 9/12-13/94 
region. In this sense, it is a safer vector. 
Dr. Parkman said that for the sake of consistency in approving protocols, he asked for 
data on preimmune animals to assess the question of inflammatory response. Most 
human patients will be seropositive for adenoviruses, but the animal experiments were all 
performed with non-immune naive animals. 
Dr. Wilson said that there are few correlates in animals that will be predictive in humans, 
and that is the main reason to perform this human study to assess toxicity. He suggested 
limiting the present study to those patients who have less risk for this complication. 
Dr. Miller asked if the preimmune cotton rat experiments will be agreeable to Dr. Wilson. 
Dr. Wilson said different toxicities in different organs in different animal species will 
complicate the risk assessment. Dr. H. Ginsberg agreed that it is an important point. For 
example, gastrointestinal tract sensitivity to adenovirus in humans does not have a parallel 
in cotton rats. 
Dr. Parkman said he would agree if the study is limited to those patients who do not have 
preexisting immunity similar to the animal experiments. But this patient population will 
be a very small percentage. 
Dr. Eck said that there are practically no brain tumor patients who have never been 
infected by adenoviruses. He suggested proceeding first with the group of patients who 
will have brain resection. If there are serious untoward reactions, they could be taken for 
surgical debulking immediately. If there are no adverse effects in this group of patients, 
then the study would be performed with the group going for stereotaxic injection alone. 
Dr. Noguchi said that FDA’s toxicologists will be more supportive if the animal data is 
available. He would encourage the investigators to perform these toxicological studies. 
Dr. H. Ginsberg remarked that the term "toxic" may be not appropriate in this case since 
the inflammation is not caused by a toxic effect of virion proteins. 
Dr. Straus said that the adverse reactions that occurred in other brain tumor protocols 
appear to be immediate hypersensitivity reactions, and similar reactions could happen in 
this case. 
Dr. Chase said that considering the threshold of patient burden even for a Phase I trial, 
this protocol is very close to the margin and that he would approve it with a great deal of 
discomfort. 
Responding to a question by Dr. H. Ginsberg about the unit of adenovirus, Dr. Eck said it 
is expressed as the pfu, plaque forming unit, throughout the protocol. 
Dr. Franck Sturtz of Progenitor, Inc., Athens, Ohio, commented that it is useful to have 
several different trials to compare the results. The RAC should propose some index to 
monitor these studies. Dr. Eck said that this protocol is a toxicity study; but he agrees 
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