Recombinant DNA Advisory Committee - 03/1-2/93 
How will efficacy by assessed? How did the investigators arrive at the proposed accrual 
of 20 patients? Dr. Van Gilder responded that patients will be evaluated on the basis of 
their Karnofsky score and by magnetic resonance imaging (MRI) and computerized 
tomography (CT) scans. Dr. Leventhal said that these procedures will indicate whether 
the tumor is growing; however, nothing will be known about the efficacy of the 
treatment. If treatment failure will be indicated by growth of the tumor, how will you 
know if the treatment has been successful? Is patient eligibility limited to those patients 
who have measurable tumors on their post-operative CT scan? Dr. Van Gilder said that 
measurable tumor post surgery would be included as an eligibility requirement. 
Dr. Van Gilder explained that it is difficult to distinguish between post-operative and 
therapeutic effects; therefore, sequential scanning is important. Although responses to 
treatment may vary, there is a consistency that is observed in response to surgery. 
Immediately following surgery, it is difficult to distinguish between residual tumor and 
edema. By the time a patient has completed their chemotherapy regimen, approximately 
6 weeks post surgery, the edema has usually disappeared. Changes are generally 
observed in the enhanced volumes of CT scans at approximately 2 months post surgery. 
Sequential scanning is essential in evaluating the efficacy of the treatment. Dr. 
Leventhal asked whether it is possible that patients will be rejected from this study if 
they have no demonstrable tumor on their post-operative CT scan. Dr. Van Gilder 
explained that this rejection would be an extremely rare occurrence because malignant 
gliomas cannot be completely resected. 
Dr. Leventhal asked how the residual tumor would be measured. Dr. Van Gilder 
explained that residual tumor is determined based on the blood brain barrier, i.e., the 
enhanced volume on the CT scan. Dr. Leventhal stated that the eligibility requirements 
should be expanded in the informed consent document to include only those patients 
who have measurable tumor as demonstrated by an immediate post-operative imaging 
procedure! 
Discussion 
Dr. Krogstad said that it is unclear how the investigators will determine if the patient's 
positive or negative response is a direct result of the gene therapy portion of the 
protocol. Dr. Leventhal agreed with Dr. Krogstad's conclusion and stated that the 
protocol should Include a statistical section which outlines how the objectives of the 
protocol correlate with the number of patients proposed, i.e., 40 patients. Dr. Culver 
said that data derived from 14 patients should provide sufficient statistical information to 
distinguish between false positive and negative responses. Dr. Leventhal explained that 
14 patients will statistically prove if there is a 95% chance that 20% of the patients may 
respond to the treatment. The maximum level of response has to be defined. If this 
therapy is toxic, then a 20% response rate may be unacceptable. If the first 14 patients 
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