Johns Hopkins Oncology Center. One day after nephrectomy, if the patient has 
histologically confirmed renal cell carcinoma, investigators will call a 
centralized registration/ randomization desk in Oncology Biostatistics. A 
eligibility check will be obtained before patients are randomly assigned 
to a treatment group. Randomization will be blocked in such a way that 
accrual for a lowest Dose Level will be filled prior to assigning any patients 
to the next higher Dose Level. If there are no dose-limiting toxicities after 
accrual of all patients required on the randomized portion of the study, 3 
additional patients will be assigned non-randomly in the gene 
transduced group at Dose Level 4. 
5.4 Early Stopping 
This study will employ the usual guidelines for Phase I dose escalation 
designs. In particular, dose-limiting toxicities observed at one Dose Level 
will require that patients be treated at the previous Dose Level in order to 
find the MTD. Because of the strict dose escalation design, we will employ no 
formal biostatistical guidelines for early termination of the study. 
5.5 Analysis of Key Endpoints 
The primary statistical endpoint of this study is to estimate the MTD if 
it exists in the dose range to be studied. The criteria for defining the MTD 
are outlined in sections 3 and 9. The assessment of this endpoint will follow 
the theory and practice recommended by Storer (1). Although recent theory and 
simulations have suggested that alternative phase I design may be more 
efficient (2-5), the present study employs a traditional phase I dose 
escalation design and analysis because the ethical criteria for alternative 
designs cannot be met. 
A second goal of this study is to determine the feasibility of this new 
form of treatment. The gene transfer success rate will be determined by the 
success rate of establishing short term cultures that provide the assigned 
dose level of RCC cells for three doses after full expansion. A second 
endpoint of feasibility will be the success rate of MFG vector GM-CSF gene 
transduction during vaccine preparation in yielding a secretion rate of 24- 
48ng/10 6 cells per 24 hour versus total attempts. These success rates will be 
determined as a proportion in the usual fashion where the denominator includes 
all patients who meet the eligibility criteria. Exact binomial confidence 
limits will be placed on each estimated proportion. 
A third goal of this study is to estimate the frequency of toxicities 
due to therapy, particular renal injury. These will be characterized 
according to the National Cancer Institute Common Toxicity Criteria and exact 
binomial confidence limits will be used to characterize the precision of the 
estimate. Other toxicities of interest include local and systemic toxicities 
associated with the RCC cells and autoimmunity. These will be treated in a 
similar fashion. Large differences in toxicity between the randomized groups 
will be characterized and noted. 
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