Recombinant DNA Advisory Committee- 9/12-13/94 
Committee Motion 
The RAC approved a motion made by Dr. Straus and seconded by Dr. Saha to accept the 
protocol submitted by Dr. Steven M. Albelda of the University of Pennsylvania Medical 
Center, Philadelphia, Pennsylvania, by a vote of 14 in favor, 0 opposed, and 1 abstention. 
Approval of the protocol is contingent on review and approval of the following by the 
primary RAC reviewers: (1) a revised Informed Consent document incorporating the 
changes suggested by Mr. Capron, and (2) revision of the sections of the protocol 
concerning the management of GCV toxicity. 
Summary 
Dr. Steven M. Albelda of the University of Pennsylvania Medical Center, Philadelphia, 
Pennsylvania, may conduct gene transfer experiments on 12 subjects with advanced 
mesothelioma. The adenovirus vector encoding the HSV-TK gene, H5.020RSVTK, will be 
administered by a chest tube into the pleural cavity. Tumor biopsies will be harvested for 
analyses for evidence of gene transfer and expression and for immunological responses to 
vector administration. GCV will be administered by intravenous infusion for 14 days. 
The primary objective of this Phase I study is to evaluate the safety and feasibility of 
treating patients with malignant mesothelioma by direct delivery of the adenovirus vector 
into the pleural cavity. 
C CLOSING REMARKS AND FUTURE MEETINGS OF THE RAC 
Mr. Capron asked if the RAC will have a working group to establish guidelines for 
adenovirus vectors. There had been a great deal of discussion involving the ad hoc 
consultant and RAC members during the course of reviewing the protocols regarding the 
safety criteria of adenovirus vectors. He asked if a working group could be established to 
examine the adenovirus vectors. Dr. Straus noted that although a significant amount of 
animal data exists, little is known with regard to safety in humans. It would not be a 
productive effort at this time to try to work out a concrete set of guidelines for the 
adenovirus vectors. Dr. Walters and Mr. Capron agreed on this assessment. 
Dr. Ross said that the issue about adenovirus vectors appears to be a procedural question 
on how to resolve the different opinions of an expert in the field and the investigators. 
Ms. Meyers said that her position is that if there is a scientific argument and it is 
uncertain who is right, she prefers to err on the side of caution and wait until it is proved 
to be safe. 
Dr. Parkman asked if the RAC should start the process to define the review criteria, or 
this task will be included in the ad hoc committee review of the RAC as suggested by Dr. 
Varmus earlier. Dr. Wivel explained that from his understanding both the issues of 
review of RAC activities and review criteria will be included in the proposed ad hoc 
external review. Dr. Walters said that, based on the RAC review experience, it is possible 
to provide some conclusive answers to the questions raised in the Points to Consider. 
Recombinant DNA Research, Volume 20 
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