Protocol HNS 94-001 
October 4, 1994 
Page 12 
initially entered at each dose level in each group (resectable and non-resectable). If one patient in 
the cohort of 3 develops grade 3 toxicity for any system except hematologic (grade 4 required), an 
additional 3 patients will be entered at that dose level. If 2 of the 6 patients develop grade 3 (grade 4 
hematologic) or greater toxicities, the next lower dose level not causing these toxicities is declared 
the Maximum Tolerated Dose (MTD). If MTD toxicity were to occur, patients couid continue treatment 
at the next lower dose level. The MTD will be determined separately for each phase of the study.lf 
MTD toxicity occurs in a cohort of 3 patients, then the next 3 patients may bypass the adenovirus 
alone phase and initially receive the adenovirus and cisplatin to establish the MTD for this 
combination. 
8.2 The tumor bed and or neck will be photographed prior to each course of therapy for aerodigestive 
tract primary lesions. 
8.3 The longest diameter and its perpendicular will be measured will be determined for measurable 
lesions. Size will be reported as the product of the diameters. 
8.4 The rate of regrowth of the tumor will be calculated from the above measurements. 
8.5 Patients will be evaluable for response if they have received at least one course of therapy. A 
complete response is defined as disappearance of all clinical evidence of tumor without the 
appearance of new lesions for a period of at least four weeks. Patients evaluable for a less-than- 
complete response must have had a bidimensionally measurable tumor. Partial response is defined as 
a 50% or greater reduction in the sum of the products of the diameters of the measurable disease; a 
minor response is defined as a 25% to less than 50% reduction in the sum of the products of the 
diameters of the measurable lesion. Patients are designated as having progressive disease if they 
show a 25% or greater increase in the size of their disease or if they develop unequivocal new lesions 
during treatment, and having no change if they have any tumor change not meeting the criteria 
described above. 
8.6 The time to progression will t^e 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. 
8.7 Alternative biologic endpoints will also be monitored. Pre-therapy and three days following the final 
treatment biopsies will be obtained and analyzed as described in section 7.5.2. Percentage of 
transfected cells in 3 random 100 x magnification fields will be determined. Maximal transduction rate 
will be determined by in-situ and immunohistochemically. 
8.8 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 immediately to the Study Chairperson, 
who in turn, must notify the IRB, RAC, and FDA. 
9.0 CRITERIA FOR DISCONTINUING THERAPY 
9.1 Progression of obstructing airway tumor that has recurred after a minimum of 2 courses of treatment. 
9.2 The development of unacceptable toxicity defined as unpredictable, irreversible, or Grade 4 (non- 
hematologic). 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. 
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