Recombinant DNA Advisory Committee- 9/12-13/94 
Research Center for the initial 3 infusions of retroviral vector. Blood will be drawn each 
day and tested for the presence of retroviral vector. Fluid sampling will be performed the 
day after infusion to obtain cell samples to determine the percentage of cells taking up the 
vector constructs and to assess the transgene expression. After the 4 day period, patients 
can receive other types of therapy. 
Responding to Ms. Meyers’ question on an alternate therapy statement for breast cancer 
in the Informed Consent, Dr. Holt said there are other systemic therapies for metastatic 
breast cancer, but the present protocol is directed to treat local disease. Dr. Parkman said 
that a statement indicating that there are no other investigational regional therapies would 
clarify this issue. Dr. D. Ginsburg said that pleurocentesis for malignant pleural effusion 
is a standard regional therapy. Dr. Arteaga said that these are therapies that patients can 
receive after completion of 4 days of vector infusion. Dr. Holt accepted Ms. Meyers’ 
suggestion that there should be statements indicating that there are other systemic 
therapies that are available. 
Dr. Parkman asked if all the scientific experiments will be performed in the first 4 days of 
the study. Dr. Arteaga said that the primary endpoint is to determine vector integration 
and expression in mammary cancer cells, and it will be done over 4 days. The second 
endpoint is the appearance of a retrovirus in the blood stream. The third endpoint is 
clinical toxicity, i.e., local peritonitis or pleuritis, and systemic symptoms such as fever and 
blood tests. Dr. Parkman commented that the local inflammatory response will be more 
critical in the study with meningeal infusion. 
Dr. D. Ginsburg said that since this treatment is local and will not have any potential 
benefit to patients, patients may not want to enroll in this study. He asked if subsequent 
therapies such as intrathecal chemotherapy will complicate the interpretation of data 
regarding retroviral infusions. He questioned if it is acceptable to ask patients with 
carcinomatosis meningitis to undergo 4 days of experiment before starting intrathecal 
chemotherapy. Dr. Smith remarked that the vector dose for meningeal study is much 
lower than that used in animal studies. Dr. Holt said that meningeal patients would 
account for less than 5 % of eligible patients, and he agreed to delete this arm of the 
study. 
Regarding the pleural effusion patients, Dr. Arteaga said that the protocol will not enroll 
patients with serious pleural effusions that require other immediate therapies. Dr. D. 
Ginsburg remarked that in this aspect the present protocol is different from other studies 
aiming at patients who have failed other standard therapies. This local therapy, which is 
similar to pleurocentesis, will not affect the outcome of the systemic metastasis of breast 
cancer. Dr. Arteaga said that the local site will allow assessment of vector treatment over 
other local chemotherapies. Dr. Miller agreed that it is a reasonable approach. Dr. Smith 
said that this protocol will yield data addressing some questions about the use of antisense 
oncogenes in human cancer. 
Responding to the question on contraception in the Informed Consent document. Dr. Holt 
said that the vast majority of patients will be post-menopausal. Ms. Meyers noted not all 
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