Recombinant DNA Advisory Committee - 3/3^/94 
Arizona, Tucson, Arizona. Dr. Doi said that this protocol is similar to other protocols 
previously approved by the RAC, i.e., Dr. Gary J. Nabel's (Protocol #9306-045), and Dr. 
Joseph Rubin's (Protocol #9312-064), and Dr. Vogelzang's protocol that was just 
reviewed and recommended for approval by the RAC. Like Dr. Nabel's protocol, this 
study involves melanoma patients. However, larger doses of the DNA/liposome complex 
are proposed for this study. These doses are in the same range as Dr. Rubin's colorectal 
cancer protocol. This Phase I protocol is a part of the multicenter study sponsored by 
Vical, Inc., to evaluate the safety and immune responses to direct intratumoral injection 
of DNA/lipid complexes containing the nonviral plasmid DNA vector, pHLA-B7/p-2 
microglobulin. This vector expresses a heterodimeric cell surface histocompatibility 
antigen which should elicit an in vivo antitumor response. Dr. Doi stated that the same 
comments regarding Dr. Vogelzang's protocol also apply to Dr. Hersh's protocol. 
Review-Dr. DeLeon 
Dr. DeLeon stated that the term "at two additional sites" should be deleted from the 
Points to Consider since only a single site is proposed for this study, the Arizona Cancer 
Center. There are several inconsistencies between the protocol and the Informed 
Consent document with regard to the study design. The protocol states that patients in 
study Arm 1 will receive a single injection, whereas the Informed Consent document 
states that multiple injections will be administered to a single nodule (up to 5 times). In 
the investigators' written response they explained that up to 5 points of injections will be 
administered into the same tumor mass to maximize contact between the DNA liposome 
and tumor cells. 
Other Comments 
Ms. Grossman said that a request for autopsy was inadvertently omitted from the 
Informed Consent document, and that the number of patients proposed for this study 
was not clearly stated in the protocol. 
Dr. Walters noted a statement in the Informed Consent document regarding 
compensation for research related injuries. The original document stated, "in the 
unlikely event of physical injury resulting from research procedures, the University will 
provide first-aid medical treatment. Treatment from injuries or side effects directly 
related to this experimental treatment will be provided at no cost to you." However, the 
revised document states "Necessary emergency medical care directly related to this 
treatment will be provided from Evan M. Hersh, M.D." Ms. Grossman inquired about 
the exact number of patients who will be entered onto the study. Dr. Walters inquired 
about the reason for this change. Dr. Secundy asked whether a request for autopsy has 
been included in the revised Informed Consent document. 
Investigator Response-Dr. Hersh 
Dr. Hersh said that Dr. DeLeon's suggestions regarding "single site" language and a 
request for autopsy will be incorporated into a revised Informed Consent document. 
Recombinant DNA Research, Volume 19 
[47] 
