an individual mass, the procedure is done with local anesthesia in an outpatient 
setting, and has been repeated 2 to 5 times over several weeks, provided regression is 
induced and appears to be continuing. For the in vivo gene transfer study, patients will 
be admitted to the Mayo General Clinical Research Center (GCRC) in Saint Mary's 
Hospital. There is an ultrasound suite with its own holding area two floors removed 
from the GCRC. 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. Following the procedure, patients are 
kept in the diagnostic radiology area for two hours to assure stability before being 
transferred, in this instance, back to the GCRC. The suite contains CT scanning 
equipment, a procedure than can be used to visualize local bleeding. 
The chemotherapy, pharmacy, and pharmacology shared resources of the Mayo 
Comprehensive Cancer Center are available and will be sued to support this project. 
Darryl Grendahl., B.S. Pharm., is in charge of the Mayo Chemotherapy Shared 
Resource and is a member of the Department of Pharmacy, Rochester Methodist 
Hospital. He 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. HLA-B7 
negative patients with colorectal cancer and hepatic metastases, two of which are 
clearly measurable by CT scan and one of which is appropriate for sonographically- 
guided biopsy and injection, will be eligible for entry into this trial. Patients must have 
failed treatment with at lease one fluoropyrimidine regimen. 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 pg. 
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 pg. The same procedure will be followed at this dose 
level before proceeding to the final dose level, 250 pg. Schedule B will be initiated in 
new patients after all 3 patients given 50pg DNA have been observed and found not to 
have unacceptable toxicity. On schedule B, 1 group of 3 patients will receive lOpg 
DNA days 1 and 15. If at 30 days no patient has unacceptable toxicity, a second group 
of 3 new patients will receive lOpg DNA on days 1, 15, and 30. 
2.0 Goals 
2.1 To determine safety and toxicity of direct intralesional injection of 
increasing amounts of a DNA/lipid mixture: VCL-1005 (HLA- 
B7/DMRIE/DOPE) into solid tumors in selected patients with metastatic 
colorectal adenocarcinoma. Escalating treatment regimens will be used 
and tumor growth evaluated. 
2.2 To measure the cytotoxic T-cell activity directed towards antigens on 
tumor cells other than HLA-B7. 
Recombinant DNA Research, Volume 18 
[761] 
