Recombinant DNA Advisory Committee - 03/1-2/93 
able to define the "X". Stable disease for a period of time is not necessarily evidence of 
a response; however, stable disease could be a criteria for approving additional 
injections. There should be a minimum period of disease stability after the third 
injection before proceeding to a fourth injection. 
Dr. Straus inquired about the practicality of determining residual tumor on a post- 
operative scan. How is residual tumor distinguished from edema? Dr. Van Gilder 
explained that it is often difficult to determine residual tumor on a post-operative scan; 
however, sequential scans are beneficial. Dr. Straus agreed with Dr. Miller that 
demonstration of residual tumor on a post-operative scan may be a moot issue in this 
uniformly fatal disease. Dr. Leventhal asserted that there are very well defined criteria 
for distinguishing between residual tumor and edema. However, performing a scan 
immediately following surgery is critical. Dr. Leventhal stated that if the investigators 
employ the criteria established by the Brain Tumor Study Group for evaluating residual 
tumor versus edema, the stipulation would be satisfied. 
Dr. Krogstad said that he would be satisfied with the approval to treat 2 or 3 patients; 
however, the end points of this study and how efficacy will be defined should be 
addressed before the approval is granted to treat additional patients. Perhaps the 
approval of additional patients could be handled as a minor modification. 
Ms. Meyers asked Dr. Culver how he would respond to any patients who requested to 
receive this therapy on a compassionate use basis. Dr. Culver said that all patients must 
meet the eligibility requirements of the protocol. If patients do not meet these 
requirements or the study is closed, they will be referred to other research protocols in 
the U.S. 
Dr. Leventhal suggested a third stipulation for approval as follows: (3) After the initial 3 
injections of the VPC and GCV therapy, patients only will be eligible for additional 
treatments if they have demonstrated stable disease for a minimum of 6 months. Dr. 
Hirano and Ms. Meyers accepted Dr. Leventhal's additional stipulation as part of the 
motion for approval of the protocol. The protocol was approved with stipulations by a 
vote of 19 in favor, 0 opposed, and no abstentions. 
IV. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: PHASE I STUDY OF GENE THERAPY 
FOR BREAST CANCER/DR. BANK 
Review— Dr. Parkman 
Dr. Walters called on Dr. Parkman to present his primary review of the protocol 
submitted by Dr. Arthur Bank of Columbia University, New York, New York. 
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