Recombinant DNA Advisory Committee- 9/12-13/94 
that in the future Phase II or III studies, the clinical trials should be so designed that data 
from different studies can be directly compared. Dr. Sturtz said that even for toxicity 
studies, indexes such as intracranial hypertension or headaches might be useful. 
Responding to a critique by Ms. Meyers, it is important to conduct different trials on the 
same disease in order to compare the outcome. 
Committee Motion 
Dr. Parkman made a motion to approve the protocol with two contingencies: (1) the 
protocol design should be revised so that the group of patients who receive stereotaxic 
injections followed by resection occur before the cohort of patients who receive the 
stereotaxic injections alone; and (2) negative results are to be obtained from intracerebral 
injections of pre-immunized cotton rats as scored by either lethality or dysfunction of the 
central nervous system. Dr. Motulsky seconded the motion. 
Dr. Eck accepted a revised Informed Consent document suggested by Mr. Capron 
concerning wording of the Expected Benefit Section of the Informed Consent document. 
It says, "Since the purpose of this study is to determine the safety of new techniques, the 
investigators do not expect that I will benefit personally from participating, although 
knowledge may be gained that may benefit others." 
Dr. Parkman said patients in group of 3 will start at the lowest dose, and then move up to 
a higher dose. Dr. Eck agreed to a 30 day period of follow-up before starting the next 
cohort. 
Dr. Noguchi commented that the cotton rat data is needed but the results do not have to 
be negative. Dr. Parkman said that if all animals die, the protocol would have to be 
reconsidered. 
Dr. Imre Kovesdi of GenVec, Inc., commented that it is simplistic thinking that leaving all 
the E3 region intact will make a safer vector. Interaction of several genes in this region 
may be important. He was cautious not to make a definitive statement regarding which 
adenovirus vector is better, since most animal studies are not conclusive in regard to 
application to the human situations. Dr. H. Ginsberg said his detailed study has been 
performed in cotton rats by deleting one gene at a time in the E3 region. 
The RAC approved a motion made by Dr. Parkman and seconded by Dr. Motulsky to 
approve the protocol submitted by Drs. Stephen L. Eck and Jane B. Alavi of the 
University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, by a vote of 15 in 
favor, 0 opposed, and no abstentions. Approval of the protocol is contingent on the 
review and approval of the following by the RAC primary reviewers: (1) A revised 
protocol design in which the first low-dose cohort will receive stereotaxic injection of the 
adenovirus vector followed by surgical resection. The second cohort will receive 
stereotaxic injection alone. Each dose of adenovirus vector will be administered in this 
manner. Each cohort will be monitored for a period of 30 days before entering the next 
cohort. If data indicate any serious untoward event, the PI will immediately notify the 
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Recombinant DNA Research, Volume 20 
