Recombinant DNA Advisory Committee - 03/1-2/93 
demonstrate no response, will the protocol be terminated? If a positive response is 
observed in 1 of the first 14 patients, will the remainder of the 40 patients be treated? 
Dr. Culver agreed to include an expanded section regarding the definition of endpoints 
as suggested by Dr. Leventhal. 
Dr. Chase inquired about the standard of statistical analysis for human gene transfer 
protocols that are approved by the RAC. Dr. Leventhal stated that investigators should 
be required to include a section that outlines the objective of the protocol and to 
describe how "X" number of patients will statistically determine that the objective has 
been achieved. The investigator is responsible for defining that objective, i.e., toxicity, 
efficacy, etc. 
Dr. Haselkom asked if the Ommaya reservoir could be used for sampling as well as for 
the administration of the VPC. Are there biochemical markers which can be used to 
determine the efficacy of the treatment using reservoir sampling? He asked Dr. Culver 
to respond to Dr. Post's question regarding immune status of patients that have been 
treated on the Oldfield protocol. Dr. Culver answered that Ommaya reservoirs are not 
designed for sampling purposes. The tubing is thin and flexible, aspiration would be 
difficult. 
Dr. Culver responded to Dr. Post's question about the immune status of patients in the 
ongoing glioblastoma protocol. Cell and serum samples have been cryopreserved for all 
patients who have received VPC and ganciclovir therapy. These samples will be 
evaluated in the future for immune responses to PA317. Data indicates that patients 
receiving 32 milligrams per day of dexamethasone are completely anergic based on 
immunologic analyses. Dr. Post inquired about the number of cells that patients have 
received to date on the Oldfield protocol. Dr. Culver answered that 5 patients have 
received one of the following numbers of VPC: 1.7 x 10 8 , 5 x 10 8 , or 1 x 10 9 cells. There 
has been no evidence of toxicity in response to any of these doses of VPC. Dr. Walters 
asked if any unexpected effects had been observed in the 5 patients treated to date. Dr. 
Culver responded that no unexpected effects have been observed as a result of the 
implantation of these VPC in patients. 
Dr. Smith reiterated that Phase II studies such as this one should include a clearer 
definition of the criteria for responsiveness. The investigators need to clarify the 
injection schedule of the VPC. If all patients receive 1 injection of VPC, what are the 
criteria for more than 1 injection? Dr. Culver said that patients must have demonstrated 
an initial response. If progressive tumor is observed soon after the first injection, e.g., 
less than 3 weeks, the patient will not be eligible for further injections. However, if 
tumor recurrence occurs several months following the initial treatment, another injection 
of VPC would be administered. 
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Recombinant DNA Research, Volume 17 
