Excellent facilities exist at the University of Chicago for carrying out sonographically- 
directed biopsy and delivery of materials at deep sites in the body. For this in vivo gene 
transfer study, patients will be admitted to the Hematology/ Oncology service at the 
University of Chicago Hospital. Invasive procedures in the ultrasound suite are carried out 
under conditions in which a general surgeon is immediately available in the extremely rare 
instance of the acute complication of bleeding. An operating room is always immediately 
available for such circumstances. A CT scanner will also be available to visualize localized 
bleeding. Following the procedure, the patient will be kept in the diagnostic radiology area 
until stable. The patient will then be transferred to the inpatient Hematology /Oncology 
ward. 
The chemotherapy, pharmacy, and pharmacology shared resources of the University of 
Chicago Cancer Center are available and will support this project. The pharmacy will 
assure the storage, preparation, and delivery of the final DNA/liposomal product to the 
ultrasound suite when needed. 
The design of this trial is similar to standard phase I clinical trials. FILA-B7 negative 
patients with metastatic renal cell carcinoma will be enrolled. Patients must have at least 2 
metastatic lesions or one metastatic lesion and an intact primary which are clearly 
measurable by CT scan and one of which is appropriate for sonographically-guided biopsy 
and injection. Patients will be treated on one of two schedules. On schedule A, the 
recombinant DNA will be administered in escalating doses to groups of 3 patients at each 
of 3 dose levels: 10, 50, and 250 meg. On schedule A, each patient will receive only a single 
injection. Each of 3 patients will be observed for toxicity and response for 30 days before 
patients will receive DNA at the next planned higher dose, 50 meg. The same procedure 
will be followed at this dose level before proceeding to the final dose level, 250 meg. 
Schedule B will be initiated in new patients after all 3 patients given 50 meg DNA have 
been observed and found not to have unacceptable toxicity. On schedule B-1, a group of 3 
patients will receive 10 meg DNA days 1 and 15. If at 30 days no patient has unacceptable 
toxicity, a second group of 3 new patients, group B-2, will receive 10 meg DNA on days 1, 
15, and 30. 
2.0 Goals 
2.1 
2.2 
2.3 
2.4 
2.5 
To determine safety and toxicity of direct intralesional injection of increasing 
amounts of a DNA/lipid mixture: VCL-1005 (HLA-B7/DMRIE/DOPE) into 
tumors in selected patients with metastatic renal cell carcinoma. Escalating 
treatment regimens will be used and tumor growth evaluated. 
To measure the cytotoxic T-cell activity directed towards antigens on tumor 
cells other than FILA-B7. 
To measure humoral and cellular immune responses to HLA-B7. 
To confirm expression in vivo of the HLA-B7 gene in the tumor cells. 
To characterize the clinical response to escalating doses of the study drug by 
assessing the size of the injected tumor and of other tumor masses that may be 
present. 
Recombinant DNA Research, Volume 19 
[213] 
