PROTOCOL THS 9<4-002 
REVISED 5/19/9A 
PAGE 9 
5.3 
5.4 
5.5 
5.6 
5.7 
5.8 
5.9 
5.10 
5.11 
5.12 
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 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). 
Dose Escalation: 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. We estimate based on the achievable titers of adenovirus that six 
dose levels can be done thus requiring 21 patients each for the intratumor and intrapleural groups 
for each of the two groups (Ad5CMV-p53 alone and Ad5CMV-p53 plus cisplatin). 
All patients shall be registered with the Data Management office at 713-792-2926. At the time of 
registration, a prestudy form shall be necessary on each patient. When applicable, information 
pertaining to important prognostic factors such as tumor histology, pretreatment weight loss, 
performance status, disease stage and extent, and prior therapy will be requested. 
Patients with local-regional tumors will have injection of a total dose of 10 ml for tumors^ 4 cm in 
diameter or 3 ml for tumors < 4 cm In diameter of the adenovirus preparation with the appropriate 
number of viral particles at multiple sites percutaneously under fluoroscopic guidance. Direct 
thoracoscopic injections may also be used. 
Patients with pleural effusion will have a Hickman chest catheter inserted to drain the effusion and 
then will have 10 ml of the adenoviral preparation instilled into a chest catheter followed by 15 ml of 
normal saline. The chest catheter will be clamped for 3 hours with the patient turned from side-to- 
side. The chest catheter will then be undamped and left to drainage. 
For patients with obstructing tumors of the bronchus, patients will undergo bronchoscopy to assess 
the degree of obstruction. As much gross tumor as possible will be resected endoscopically. 
Patients may also have had brachytherapy as a tumor reduction modalitv. Patients will undergo 
bronchoscopy under topical or general anesthesia. A Stifcor"" transbronchial aspiration needle (21 g) 
will be passed through the biopsy channel of the bronchoscope. The residual tumor site will be 
injected with 10® PFU of the adenovirus supernatant as the starting dose level. The volume will be 
no greater than 3 ml. Injections will be circumferential and will be intratumor and submucosal. 
The treatment will be repeated monthly. Dose escalation may proceed after a minimum two week 
follow-up of the last patient entered into the previous dose level. Treatment will continue as long as 
there is no tumor progression. After one year the patients will be evaluated for continuation of 
therapy. 
Patients will wear a surgical mask for 24 hours following injection of the adenovirus. All medical 
personnel will wear masks and face shields routinely during bronchoscopy and injection of the 
adenovirus. Anti-tussives will be prescribed as necessary. All patients will be kept in isolation during 
the time they are receiving injections of the adenovirus and for 48 hours after the last injection. 
Chemotherapy 
Dose Schedule: The dose levels and schedule will be as follows: 
DRUG 
DAYS DAILY DOSE LEVELS 
(mg/m* IV) 
-2 -1 0 
Cisplatin 
1-3 20 25 30 
(598] 
Recombinant DNA Research, Volume 19 
