Recombinant DMA Advisory Committee - 3/^/94 
biopsy. Dr. Sudakoff possesses a great deal of expertise in performing this technique and 
his biographical sketch has been submitted for review. Responding to Dr. Walters' 
question about frequent metastatic sites, Dr. Vogelzang said that most renal cell 
carcinoma metastasis are in visceral organs such as the lung, liver, mediastinal, and 
retroperitoneal lymph nodes. Such locations are in contrast to the subcutaneous sites of 
metastases in melanoma patients. In response to Ms. Grossman's question. Dr. 
Vogelzang stated that Dr. Nabel will not be directly involved in this study. The multi- 
center trial will be coordinated by Vical, Inc., San Diego, California, and the company 
has selected a central laboratory to perform the immunological assays. Dr. Parkman 
asked about the size of the tumor in relation to the dose of DNA to be injected. Dr. 
Vogelzang said that most metastatic tumors are 2 to 4 cm in diameter. The primary 
tumors are much larger and necrotic and are not suitable for injection. 
Dr. George Gray explained that Dr. Nabel has served on the Scientific Advisory Board 
of Vical, Inc., and has chaired the Oncology Task Force that decides issues such as the 
tumor types and institutions that will be involved. Dr. Evan Hersh, Principal Investigator 
of the Arizona Cancer Center study, will oversee the central laboratory that will perform 
the immunological assays for all sites. Vical will establish the procedures for testing and 
evaluate the results from all study sites. Dr. Nabel is conducting an independent 
protocol that is not considered part of this multi-center study. Dr. Nabel has an 
investigator sponsored IND, whereas, Vical has an institutional sponsored IND. Dr. Doi 
asked about the proposed DNA/liposome dose as compared with that of Dr. Nabel's 
study. Dr. Gray responded that the present dose of 10, 30, and 300 micrograms is 
bracketed between the highest and the lowest dose of Dr. Nabel's study, i.e., 3 to 500 
micrograms. 
Dr. Walters stated that the abstracts contain language that implies that there is a 
therapeutic intent. Such language is not appropriate for a Phase I study. Dr. Vogelzang 
responded that the abstracts will be modified to reflect this concern. 
Committee Motion 
A motion was made by Dr. DeLeon and seconded by Dr. Doi to approve the protocol. 
The motion passed by a vote of 13 in favor, 0 opposed, and no abstentions. 
XIII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: PHASE I STUDY OF 
IMMUNOTHERAPY OF MALIGNANT MELANOMA BY DIRECT GENE 
TRANSFER/DRS. HERSH, AKPORIAYE, HARRIS, STOPECK, UNGER, AND 
WARNEKE 
Review-Dr. Doi 
Dr. Walters called on Dr. Doi to present his primary review of the protocol submitted by 
Dr. Evan M. Hersh of the Arizona Cancer Center and Drs. Emmanuel Akporiaye, David 
Harris, Alison T. Stopeck, Evan C. Unger, and James A. Warneke of the University of 
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Recombinant DNA Research, Volume 19 
