Recombinant DNA Advisory Committee - 12/1-2/94 
tumors. 
The RAC approved a motion made by Dr. Miller and seconded by Dr. Haselkom to accept the protocol 
submitted by Drs. Hersh, Akporiaye, Harris, Stopeck, Unger, and Warneke, by a vote of 13 in favor, 0 
opposed, and 1 abstention. Approval of the protocol is contingent on review and approval of the following by 
Drs. Miller, Saha, and Zallen: (1) verification of the vector sequence, and (2) a revised Informed Consent 
document incorporating the changes suggested by Dr. Zallen. 
Dr. Erickson abstained from voting due to his affiliation with the same institution. Mr. Capron commented 
that the investigators have efficiently responded to the questions raised by the RAC, and that the protocol was 
reviewed within the time limit of the agenda. He reminded other investigators to follow the same rule to limit 
their oral responses to the RAC’s questions. The presentation of data not submitted 2 weeks prior to the 
meeting is prohibited. The investigators for the previously reviewed protocol overlooked these criteria. 
Summary 
Dr. Evan Hersh, Emmanuel Akporiaye, David Harris, Alison Stopeck, Evan Unger, and James Warneke, of 
the Arizona Cancer Center, Tucson, Arizona, may conduct gene transfer experiments on 25 subjects (£18 years 
of age) with advanced solid malignant tumors or lymphoma. Subjects will receive intratumoral injection of the 
plasmid DNA/lipid complex, VCL-1102, which encodes the IL-2 gene in an attempt to induce an antitumor 
response. The objectives of this study are to determine: (1) safety and toxicity associated with escalating 
doses of VCL-1102; (2) IL-2 expression in tumor cells; (3) biological activity and pharmacokinetics; and (4) 
whether expression of IL-2 stimulates tumor regression. 
X. ADDITION OF APPENDIX D OF THE NIH GUIDEUNES REGARDING A HUMAN GENE TRANSFER 
PROTOCOL ENTITLED: CLINICAL PROTOCOL FOR MODIFICATION OF TUMOR SUPPRESSOR 
GENE EXPRESSION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC) WITH AN 
ADENOVIRUS VECTOR EXPRESSING WILD-TYPE P53/ DR. CLAYMAN 
Review-Dr. BrinckerhofT 
Dr. Walters called on Dr. Brinckerhoff to present her primary review of the protocol submitted by Dr. Gary 
dayman of MD Anderson Cancer Center, Houston, Texas. Dr. Brinckerhoff stated that head and neck 
squamous cell carcinoma (HNSCC) is among the most frequent cancer, accounting for nearly 45,000 new 
cancers per year in this country and throughout the world. Mortality remains at nearly 55% and has not 
changed since contemporary radiation therapy was implemented over 30 years ago. This disease may have 
profound effects on speech, swallowing, and the appearance of affected individuals. Patients who have failed 
local and regional therapy usually have a median survival of 6 months. Subjects with recurrent head and neck 
cancer exhibit readily accessible tumors that can be measured, treated, and biopsied without significant 
discomfort to the patient. 
The replication defective adenovirus vector will be Ad5CMV-p53, introduced into the patient’s tumor cells to 
determine whether a normal copy of the p53 tumor suppressor gene can slow or inhibit tumor cell growth. 
The objectives of this study are to: (1) determine the maximum tolerated dose of the adenovirus vector, (2) 
determine the qualitative and quantitative toxicity and reversibility of toxicity of this treatment, and (3) 
document the antitumor activity. Subjects will be divided into 2 groups: (1) those who have advanced 
inoperable HNSCC cancer, and (2) those who are surgically resectable but not surgically curable. Subjects will 
receive an initial vector dose of 1 x 10 6 plaque forming units (pfu). Three subjects will be entered at each dose 
level with 6 patients entered at the maximum tolerated dose. Treatment will be repeated 3 times per week for 
2 weeks. Treatment will continue on a monthly basis in the absence of tumor progression or adverse 
reactions. 
Dr. Brinckerhoff stated that the rationale and experimental design for the proposed study are reasonable. The 
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Recombinant DNA Research, Volume 20 
