t 
protocol THS 94-002 , 
PROTOCOL ABSTRACT REVISED 5/19/94 | 
PAGE 1 of 2 1 
Protocol: (Give number and abbreviated title) ii 
i j 
Clinical Protocol for Modification of Tumor Suppressor Gene Expression and Induction of | 
Apoptosis in Non-Small Cell Lung Cancer (NSCLC) with an Adenovirus Vector Expressing \ 
WUdtype p53 and Cisplatin j 
Study Chairman: 
Pa tient Eligibility: 
Patients must have histologic proof of non-small cell lung cancer. Patients must be either ! 
unresectable, unable to receive primary external beam radiation therapy, or have failed primary 1 
external beam radiation therapy, or have failed chemotherapy. i 
Patients must have either an endobronchialtumor accessible by the bronchoscope, with some i 
clinical evidence of bronchial obstruction, advanced local-regional cancer which is unresectable, i 
or malignant pleural effusion. i 
All patients must have a life expectancy of at least 1 2 weeks and must have a performance ■, 
status of j^2 (Zubrod scale. Appendix B). 
A tumor biopsy must show a p53 mutation by single-strand conformation analysis. I 
Patients will be tested for HIV prior to entry onto the protocol and must be HIV-negative. 
Patients must have adequate bone marrow function (defined as peripheral absolute I 
granulocyte count of > 2,000/mm^ and platelet count of 1 00,000/mm^), adequate liver function jj 
(bilirubin ^1.5 mg/dl), and adequate renal function (creatinine <1.5 mg/dl). 
Jack A. Roth, M.D. 
Tr eatment Plan: (Include dose adjustment) 
fl 
The study will be done in two phases. It is not known what toxicities if any will be caused 
by the adenovirus. The first phase of the study will allow assessment of toxicities related only 
to the vector. Patients will receive one intratumor or intrapleural injection of Ad5CMV-p53. 
The initial dose will be 1 0® plaque forming units (PFU). Following completion of the first vector- 
alone group, a second phase will evaluate Ad5CMV-p53 and cisplatin administered 
concurrently. Patients in the second group will receive one intratumor or intrapleural injection 
of Ad5CMV-p53 with concurrent cisplatin at 30 mg/m^ with 2 additional doses of cisplatin on 
days 2 and 3. Three patients will be entered at each dose level with 6 patients entered at the 
maximum tolerated or maximum attainable dose (limitation imposed by production of the 
adenovirus) for each group. The adenovirus dose will increase in one log,o increments for-each 
group. Patients entered at a given dose level will not be eligible for dose escalation. Dose 
escalation will proceed separately for the intratumor injection group and the intrapleural 
injection group. The dose of cisplatin will remain constant. 
[5881 
Recombinant DNA Research, Volume 19 
