I 
0.2 The longest diameter and its perpendicular will be measured. Size will be reported as the product 
of the diameters. 
8.3 The rate of regrowth of the tumor will be calculated from these measurements. 
8.4 Time to Progression and Survival Duration: The time to progression will be measured from the 
first observation with reduction in tumor bulk until there is evidence of progressive disease. 
Progressive Disease is defined as an increase of > 25% in the sum of the products of the 
diameters of the measured lesion. Patients must have received at least two courses of therapy 
before a designation of progression is made. The survival of patients will be measured from entry 
into protocol. 
8.5 All toxicities encountered during the study will be evaluated according to the grading system (0- 
4) in Appendix C and recorded prior to each course of therapy. Duration of the toxicity and its 
treatment will be recorded. Life-threatening toxicities should be reported inriediately to the 
Study Chairperson, who in turn, must notify the IRB, RAC, and FDA. 
8.6 Potential risks of retroviral gene transduction 
8.6.1 Insertional mutagenesis . The possibility of causing malignancy in normal cells secondary 
to random insertion of the retroviral vector in the genome exists although this risk is 
thought to be very low. Tests of viral supernate will be conducted to assure that no 
replication competent virus is present. Non-replicating bronchial epithelial cells do not 
take up the vector in the mouse studies. 
8.6.2 Risk from murine retrovirus . The retrovirus derived from the Moloney murine leukemia 
virus is modified so that it no longer contains intact viral genes. Thus, it cannot 
produce an intact infectious virus. Assays will be performed on the retroviral vector 
supernate and the packaging cell to insure that replication competent virus is not 
present (see Section 3.0). Extensive safety studies have been performed on related 
retroviral constructs in primates. Large infusions of infectious murine amphotrophic virus 
produce no acute pathologic effects. Primates have also received retroviral gene-modified 
autologous bone marrow cells with no evidence of toxicity as long as 4 years after 
infusion”. 
8.6.3 Efficacy of aminoglycoside antibiotics . The neomycin resistance gene product, neomycin 
phosphotransferase, phosphorylates the 3’ hydroxyl group of the aminohexose I of neomycin 
and its analogues. Amikacin, but not gentamicin and tobramycin which do not contain an 
hydroxyl at the 3" position, is inactivated. Thus, induction of the neomycin resistance 
gene would not exclude aminoglycosides or any other conventional antibiotic from use in 
these patients. 
9.0 CRITERIA FOR DISCONTINUING THERAPY 
9.1 Increasing endobronchial tumor (greater than 25% increase in product of perpendicular diameters) 
after a minimum of 2 or more courses of therapy. 
9.2 The development of unacceptable toxicity defined as unpredictable, irreversible, or Grade 4. 
Patient refusal of therapy due to a specific toxicity should be graded as 4 and an explanatory 
note recorded. 
9.3 Non-compliance by patient with protocol requirements. 
9.4 Patient refusal to continue treatment. 
9.5 Criteria for removal from protocol: 
a) Refusal to continue study participation 
b) Significant hemoptysis 
c) Coagulopathy 
d) Progressive postobstructive pneumonia 
10.0 DATA AND PROTOCOL MANAGEMENT 
10.1 Protocol Compi i ance : The attending physician and oncology research nurse must see patients prior 
to drug acknini strati on. All required interim and pretreatment data should be available and the 
physician must have a designation as to tumor response and toxicity grade. 
10.2 Data Entry: Data must be entered into the Clinical Data Management System before a course of 
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