Protocol HNS 94-001 
October 4, 1994 
Page 10 
maximum attainable dose (limitation imposed by production of the adenovirus). 
5.4 Dose Escalation: The adenovirus dose will increase in one logio increments for each group. 
Patients entered at a given dose level will not be eligible for dose escalation. We estimate based on 
the achievable titers of adenovirus that six dose levels can be done thus requiring 21 patients, in each 
group (resectable and non-resectable). 
5.5 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. 
5 . 6 Patients with local-regional tumors will have injection of a total dose of 1 0 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 or transorally. Direct endoscopic injections 
may also be used is required. Injections will be placed at approximately 1 centimeter increments. 
5.7 The treatment will be repeated three times weekly for two weeks. Dose escalation may proceed after 
a minimum two week follow-up of the last patient entered into the previous dose level. Treatment will 
continue on a monthly basis as long as there is no tumor progression. After one year the patients will 
be evaluated for continuation of therapy. 
5.8 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 endoscopy 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. 
5.9 Those patients with surgically resectable disease will be treated by tumoral injection of adenovirus 
preparation as described in 5.6 and 5.7. The treatment will be repeated for two consecutive courses. 
Within four days of completion of the second course, the patients will be eligible to proceed with 
surgical resection. At the completion of surgical resection, prior to closure, 10ml of adenovirus 
preparation will be administered into the surgical defect (operative bed) and allowed to remain in 
contact for 60 minutes. The wounds are then closed and drains placed. Post-operatively, on the third 
post-operative day (prior to drain removal), 10ml of adenovirus preparation is sterily introduced into 
the drains and retrograde placed into the wounds and is allowed to remain for two hours. The drains 
are then replaced to suction and removed when indicated by the attending staff surgeon. 
6.0 PRE-TREATMENT EVALUATION 
6.1 A complete history and physical to include performance status, recent weight loss, usual weight and 
concurrent non-malignant disease and its therapy, and all prior anticancer treatments must be 
recorded. 
6.2 Laboratory studies shall include quantitative immunoglobulins; a CBC with differential and platelet 
count; SMA-12 and electrolytes, including creatinine, bilirubin, SGPT, alkaline phosphatase, HIV 
analysis, urinalysis, and chest x-ray. 
6.3 Any residual toxicity from prior therapies should be recorded using the grading schema in Appendix 
C. 
6.4 Appropriate studies should be obtained to fully define the extent and severity of existing or 
suspected malignant and non-malignant disease. 
6.5 Measurements of disease that can be measured on a C.T. scan of the head and neck will be 
documented. The location and size must be recorded prior to treatment. A photograph of the area 
will be taken at a fixed distance from the lesion. The area will be measured in 2 dimensions (product of 
Recombinant DNA Research, Volume 20 
