Scientific Abstract 
Brief Scientific Abstract: Clinical Protocol for Modification of Tumor Suppressor Gene 
Expression in Head and Neck Squamous Cell Carcinoma (HNSCC) with an Adenovirus 
Vector Expressing Wildtype p53 
Principal Investigator: Gary L. Clayman, D.D.S., M.D. 
Institution: The University of Texas M. D. Anderson Cancer Center 
OBJECTIVES 
1 ) To determine the maximum tolerated dose of the wild-type p53 adenovirus vector in patients with 
refractory HNSCC. 
2) To determine the qualitative and quantitative toxicity and reversibility of toxicity of this treatment 
approach. 
3) To document observed antitumor activity of this treatment approach. 
BACKGROUND AND RATIONALE 
Head and Neck Squamous Cell Carcinoma mortality remains at nearly 50% and has not 
significantly changed since contemporary radiation therapy was implemented over thirty years ago. 
Local/regional control remains a major issue in this patient population with only approximately 1 0% of 
patients with advanced disease succumbing to distant disease alone. The goal of this research is to 
directly modify the cancer cell to express large quantities of exogenously introduced wild-type p53 tumor 
suppressor gene product that suppresses the characteristics of the malignant phenotype with no long- 
term effect upon non-malignant tissues or the cancer patient. 
PATIENT ELIGIBILITY (Critical inclusion criteria listed only) 
1 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 ex- 
tensive 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. 
2 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. 
TREATMENT PLAN 
1 The study will be an open-label upward dose ranging study for adenovirus-p53 vector (Ad5CMV- 
p53). Two study patient groups will consist of a) resectable and b) non- resectable recurrent 
disease. It is not known what toxicities if any will be caused by the adenovirus. 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). 
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 is described within the enclosed protocol. 
2 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. Injections will be placed at 
approximately 1 cm increments. 
3 The treatment will be repeated 3 times weekly for 2 weeks. Treatment will continue on a monthly 
basis as long if there is no tumor progression. After one year the patients will be evaluated for 
continuation of therapy. 
4 Those patients with surgically resectable disease will be treated by tumoral injection of adenovirus 
preparation as described in 2 and 3. The treatment will be repeated for 2 consecutive courses. 
Within 4 days of completion of the 2nd course, the patients will be eligible to proceed with surgical 
resection. At the completion of surgical resection, prior to closure, 1 0ml of adenovirus prepara- 
tion 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 3rd post- 
operative day (prior to drain removal), 10ml of adenovirus preparation is sterilely intro-duced into 
the drains and retrograde placed into the wounds and allowed to remain for 2 hours. The drains 
are then replaced to suction and removed when indicated by the attending staff surgeon. 
Recombinant DNA Research, Volume 20 
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