Recombinant DNA Advisory Committee - 12/1-2/94 
Dr. Scheiber clarified Dr. Saha’s concern about the sensitivity of the PCR assay (60 copies of the plasmid in 1 
mg sample of total DNA). With this assay, plasmid DNA sequences can be detected at 1 week and 1 month 
following intravenous injection of high vector doses. Intravenous injection is intended to represent a worst 
case scenario, i.e., leakage to the blood circulation. Most of the plasmid DNA injected into tumors is rapidly 
degraded in situ. Once the supercoiled circular DNA is nicked by the enzyme, expression of IL-2 cDNA is 
greatly reduced. 
Dr. Hersh said that patients will be offered multiple treatment options including no further therapy (supportive 
care at home), referral to other institutions, and gene therapy. The patients are referred to the Arizona 
Cancer Center by community medical oncologists; therefore, a second opinion has already been provided. Dr. 
Hersh agreed to revise the Informed Consent document according to Dr. Zallen’s suggestions. Dr. Hersh 
stated that subjects referred to the Arizona Cancer Center have already made the decision to participate in 
this study; therefore, the 24 hour minimum waiting period protects subjects from making a hasty decision 
about participation. The 2 week maximum period is included to minimize any substantial changes in the 
patient’s disease status and maintain consistency for data evaluation. Patients are informed that this protocol 
is a Phase I study designed to determine safety and the maximally tolerated dose and the biological activity of 
the construct. Potential subjects are informed of the experimental nature of the study and that no therapeutic 
benefit is expected. The history of most Phase I therapeutic studies suggests that approximately 20% would 
show some evidence of therapeutic effect. Dr. Hersh agreed to delete this Phase I trial information from the 
Informed Consent document if the RAC has concerns about this statement. Dr. Zallen requested that the 
statement be deleted from the Informed Consent document. 
Dr. Hersh explained the following reasons for not limiting the types of solid tumors to melanoma and renal 
cell carcinoma. Animal model studies have shown that IL-2 may be effective against other solid tumors, e.g., 
lymphoma and colon cancer. He stated his preference for maintaining the broader approach. A variety of 
tumor types will provide an opportunity to obtain a broader range of information that will be useful for the 
design of future Phase II trials. The antitumor mechanism of IL-2 is different for immunotherapy than 
systemic IL-2. Systemic delivery induces lymphokine activated killer cells. IL-2 expression has been achieved 
with a variety of tumor cells in vitro including hepatocellular carcinoma, melanoma, renal cell carcinoma, 
breast cancer, and ovarian cancer. 
Dr. Hersh agreed to clarify the Informed Consent document regarding the patient’s responsibility for medical 
costs. When subjects are referred by their oncologists, the basic medical tests have been already conducted. 
Once the subject enters the protocol, essentially all costs for physician visits, administration of the agent, 
follow-up CT scans and other services are covered. The patient’s third party insurance is expected to cover the 
costs of conventional follow-up. 
Dr. Hersh agreed to clarify the statement in the Informed Consent document regarding the cost of treating 
any adverse effects. He said that two minor adverse events were observed in the previous trial (Protocol 
#9403-072). One patient required overnight hospitalization for treatment of severe pain in the injected 
nodule. All of the expenses for this hospitalization were covered by the sponsor. Efforts will be made to 
admit patients who do not have any health insurance. In such cases, the physicians charges will be waived, an 
effort will be made to obtain free medication from pharmaceutical companies, and the hospital will be 
petitioned to waive the cost of hospitalization. Since 90% of the anticipated costs will be covered by the 
sponsor, cost should not be a decisive factor to subjects considering participation. 
Committee Motion 
A motion was made by Dr. Miller and seconded by Dr. Haselkorn to approve the protocol contingent on 
incorporation of suggested changes to the Informed Consent document and clarification of minor 
inconsistencies in the IL-2 DNA sequence. 
Dr. Parkman said the investigators have made a reasonable argument for inclusion of a broad range of solid 
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