PROTOCOL ABSTRACT 
Protocol HNS 94-001 
October 4, 1994 
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Protocol: (Give number and abbreviated title) 
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Clinical Protocol for Modification of Tumor Suppressor Gene Expression and Induction of Apoptosis in Head and Neck 
Squamous Cell Carcinoma (HNSCC) with an Adenovirus Vector Expressing Wildtype p53 
Study Chairman: 
Patient Eligibility: 
Gary L. Clayman, D.D.S., M.D., Department of Head and Neck Surgery 
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Patients must have histologic proof of squamous cell carcinoma of the head and neck. Patients must be either unable to 
receive conventional treatment (e.g. the patient received radiation therapy with or without surgery) or have failed 
conventional treatment Those patients with extensive local or regional disease that have persisted or recurred following 
radiation therapy (with or without chemotherapy or surgery) and have clinically resectable, but likely non-curable ( <10% 
disease free survival) are also eligible. Patients need not have received a trial of chemotherapy prior to entering this 
protocol. All eligible patients will be discussed at the Head and Neck Surgery Multidisciplinary Treatment Planning 
Conference prior to protocol enlistment. 
Patients must have clinical evidence of advanced local and/or regional cancer which is unresectable or for which no 
meaningful resection with surgical margins will be obtainable.- • 
All patients must have a life expectancy of at least 12 weeks and must have a performance status of <2 (Zubrod scale. 
Appendix B). 
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. 
Patients will be tested for HTV prior to entry onto the protocol and must be HTV-negative. Patients with upper respiratory 
infections will not be treated until the infection resolves. 
Patients must have adequate bone marrow function (defined as peripheral absolute granulocyte count of >2, 000/mm 3 and 
platelet count of 100,000/mm 3 ), adequate liver function (bilirubin ^1.5 mg/dl), and adequate renal function (creatinine <1.5 
mg/dl). 
Treatment Plan: (Include dose adjustment) 
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The study will be an open-label upward dose ranging study for adenovirus-p53 vector (Ad5CMV-p53) in two patient groups. 
The two groups of patients will consist of a) resectable and b) non-resectable recurrent disease. The first phase of the study 
will allow assessment of toxicities related only to the vector. Patients will receive one intratumor injection of Ad5CMV-p53. 
The initial dose will be 10 6 plaque forming units (PFU). 
Dose Escalation: The adenovirus dose will increase in one logjo 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). 
All patients shall be registered with the Data Management Office at 713-792-2926. 
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 or transoraJly. 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. 
Those patients with surgically resectable disease will be treated by tumoral injection of adenovirus preparation as described 
above. 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. Prior to surgical closure, 10 ml 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. 
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Recombinant DNA Research, Volume 20 
