ABSTRACT 
"Clinical Protocol for Modification of Oncogene and Tumor Suppressor Gene Expression 
in Non-Small Cell Lung Cancer (NSCLC)", Jack A. Roth, M.D., Study Chairman 
The objective of this protocol is to evaluate the toxicity and possible therapeutic 
efficacy of the intralesional administration of retroviral constructs containing 
antisense (AS) K-ras (for tumors with mutated K-ras) and wildtype p53 (wt p53) (for 
tumors with mutated or deleted p53) into residual endobronchial NSCLC which 
obstructs a bronchus and which is refractory to conventional therapy. 
PATIENT ELIGIBILITY 
1) 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 external beam radiation therapy. 
2) Patients must have an endobronchial tumor accessible by the bronchoscope. 
There must be some clinical evidence of bronchial obstruction. 
3) All patients must have a life expectancy of at least 12 weeks and must have a 
performance status of <2 (Zubrod scale, Appendix B). 
4) All patients must sign an informed consent indicating that they are aware of 
the investigational nature of this study in keeping with the policies of the 
hospital. The only acceptable form is the one attached at the end of this 
protocol . 
5) A tumor biopsy must show either a K-ras mutation or a p53 mutation by single- 
strand conformation analysis. 
TREATMENT PLAN 
1) Patients will undergo bronchoscopy to assess the degree of obstruction. As 
much gross tumor as possible will be resected endoscopical ly . Patients may 
also have had brachytherapy as a tumor reduction modality. 
2) Patients will undergo bronchoscopy under topical or general anesthesia. A 
Stifcor tm transbronchial aspiration needle ( 2 lg ) will be passed through the 
biopsy channel of the bronchoscope. Tumor will be debulked endoscopical ly. The 
residual tumor site will be injected with 10 7 CFU/ml of the appropriate 
retroviral supernatant. The volume will be no greater than 10 ml. Injections 
will be circumferential and will be intratumor and submucosal. The AS-K-ras 
supernatant will be used for K-ras mutations and the p53 supernatant will be 
used for p53 mutations. The injections will be repeated daily for five 
consecutive days. The treatment will be repeated monthly. 
PRETREATMENT EVALUATION 
Pretreatment evaluation will consist of a complete history and physical including 
performance status, weight loss, description of previous and current malignant and 
non-mal ignant diseases and their treatment, and residual toxicities; location and 
size of the endobronchial lesion; chest x-ray, and laboratory studies including: 
quantitative immunoglobulins; a CBC with differential and platelet count; SMA-12 and 
electrolytes, including creatinine, bilirubin, SGPT, alkaline phosphatase, and 
urinalysis. 
Prior to each course of therapy, the following clinical data will be ascertained and 
recorded: 
1. CBC, platelet count, PT, PTT, SMA-12, electrolytes, and a chest x-ray. 
2. Measurement and bronchoscopic photograph of tumor. 
3. All relevant information regarding drug dosage, tumor response, laboratory 
examinations, and treatment-related toxicities. 
The primary endpoint of the study will be regrowth of the tumor. The effect of 
therapy in this group of patients will also be measured by determining length of 
patient survival, length of time the affected lobe of the lung remains aerated, and 
reduction in measurable endobronchial tumor. A maximum of 14 patients will be 
recruited in this study. 
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Recombinant DNA Research, Volume 16 
