• Safety at weeks 2-4 and then for 6 months [ Designated as safety issue: Yes ]
  
• Maximum tolerated dose of Ad5CMV-p53 gene administered as an oral rinse at weeks 2-4 and then for 6 months [ Designated as safety issue: Yes ]
  
• Transduction and efficiency of treatment as measured by Simon's optimal 2-stage design at weeks 2-4 and then for 6 months [ Designated as safety issue: No ]
  

• Effect of p53 gene transfer on molecular biomarkers of p53 activity reduction as measured by immunohistochemical staining at baseline and during courses 1 and 6 [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the acute toxic effects of Ad5CMV-p53 gene administered as an oral rinse and as an intramucosal injection in patients with diffuse premalignant carcinoma of the oral cavity or oral pharynx.
• Determine the maximum tolerated dose of this drug in these patients.
• Determine the topical transduction efficiency of adenoviral-mediated wild type p53 gene transfer in patients treated with this drug.
• Determine the efficacy of this drug in reversing the histology of oral premalignancies in these patients.
• Determine the distribution of transgenic protein within the area of the premalignant lesion in patients treated with this drug.

OUTLINE: This is an open-label, dose-escalation study of Ad5CMV-p53 gene administered as an oral rinse.

• Phase I: Patients receive Ad5CMV-p53 gene by intramucosal injection into the area of the lesion followed at least 2 hours later by Ad5CMV-p53 gene as an oral rinse on day 1. Patients then receive Ad5CMV-p53 gene as an oral rinse twice daily on days 2-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of Ad5CMV-p53 gene as an oral rinse until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive treatment with intramucosal Ad5CMV-p53 gene as in phase I and Ad5CMV-p53 gene as an oral rinse at the MTD.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years. Patients then receive long-term follow-up annually for an additional 10 years.

PROJECTED ACCRUAL: A total of 18-51 patients (18 for phase I and 33 for phase II) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed mild to moderate dysplasia OR severe dysplasia/carcinoma in situ of the oral cavity or oral pharynx

  • Clinically evident diffuse premalignant disease, defined by 1 of the following mucosal abnormalities:

    • Extension between adjacent organ structures (e.g., lateral tongue, ventral tongue, and the floor of the mouth)
    • Extensive surface area, including the entire ventral tongue or floor of the mouth or buccal mucosa, in a velvety "indiscreet" pattern

• Meets 1 of the following criteria:

  • Previously treated with conventional treatment (e.g., radiotherapy or surgery) for a prior head and neck malignancy
  • Failed biochemoprevention approaches for premalignant disease
  • Failed other therapeutic approaches for premalignant disease
• No active squamous cell carcinoma of the head and neck

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.0 mg/dL

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No hypertension (baseline blood pressure 140/90 mm Hg or higher)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 1 year after study participation
• HIV-1 negative
• No known contact with former tissue or organ transplantation recipients or individuals with severe immunodeficiency disease (acquired or congenital) during and for 28 days after study treatment
• No prior malignancy within the past 2 years except nonmelanoma skin cancer or aerodigestive cancer
• No active systemic viral, bacterial, or fungal infections requiring treatment
• No serious concurrent illness that would preclude study compliance and follow-up
• No psychological, familial, sociological, geographical, or other condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• More than 21 days since prior chemotherapy (42 days for mitomycin and nitrosoureas)
• No concurrent systemic chemotherapy

Endocrine therapy

• No concurrent prednisone or the equivalent, including corticosteroids of more than 10 mg/day

Radiotherapy

• See Disease Characteristics
• More than 3 months since prior radiotherapy involving the lesion selected for this study
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• More than 8 weeks since prior investigational agents
• No prior experimental therapy (i.e., oral, systemic, topical, or direct injection) for the lesion selected for treatment in this study
• No other concurrent immunosuppressive therapy
• No other concurrent investigational agents
• No concurrent aspirin dose greater than 175 mg/day