RATIONALE: Inserting the gene for p53 into a person's tumor may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of gene therapy in treating patients with recurrent head and neck cancer.

Condition	Treatment or Intervention	Phase
recurrent squamous cell carcinoma of the hypopharynx recurrent squamous cell carcinoma of the larynx recurrent squamous cell carcinoma of the lip and oral cavity Quality of Life recurrent squamous cell carcinoma of the oropharynx recurrent metastatic squamous neck cancer with occult primary recurrent squamous cell carcinoma of the nasopharynx recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity	Drug: Ad5CMV-p53 gene	Phase II

Further Study Details: 

OBJECTIVES: I. Estimate the objective response rate of Ad5CMV-p53 in patients with recurrent squamous cell carcinoma of the head and neck.

II. Evaluate the duration of response, time to disease progression, and overall survival of these patients after this treatment.

III. Evaluate the effectiveness of Ad5CMV-p53 in reducing cancer morbidity (pain assessment, analgesic consumption, and Karnofsky performance status).

IV. Assess the quality of life of these patients receiving this treatment.

PROTOCOL OUTLINE: This is a multicenter, open label study.

All patients receive direct intratumoral injections of Ad5CMV-p53 on days 1, 2, and 3 of each 4-week treatment course. Patients are treated for at least 2 courses barring local disease progression or unacceptable adverse events; patients with responding or stable disease receive a maximum of 12 courses. Patients are evaluated for safety 4 weeks from the completion of the last treatment. All patients complete a quality of life assessment before, during, and after treatment.

Patients are followed every 2 months for up to 18 months or until death.

PROJECTED ACCRUAL: A maximum of 39 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven squamous cell carcinoma of the head and neck
• Recurrent disease documented by histology or cytology (excluding endolaryngeal recurrence) following first line therapy with curative intent, such as: Radiation (at least 5000 cGy by standard methodology) and/or Surgery (definitive resection with postoperative radiation as indicated)
• Lesions accessible to intratumoral injections
• Bidimensionally measurable disease; The sum of the products of the bidirectional measurements for all bidimensionally measurable lesions must be not greater than 30 cm2; The sum of the longest diameters of all measurable lesions must be not greater than 10 cm
• No CNS metastasis
• Tumor tissue from biopsy of primary or recurrent tumor must be available to determine p53 mutation status

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent immunostimulating drugs; No prior autologous or allogeneic organ or tissue transplant
• Chemotherapy: At least 4 weeks since prior chemotherapy; At least 6 weeks since nitrosourea or mitomycin; No other concurrent chemotherapy
• Endocrine therapy: No concurrent nontopical corticosteroids unless chronic (at least 6 months) at low doses (no greater than 10 mg of oral prednisone)
• Radiotherapy: See Disease Characteristics; At least 4 weeks since radiotherapy to measurable disease sites, unless progressive disease; No concurrent radiotherapy to disease sites receiving study drug injections
• Surgery: See Disease Characteristics; No concurrent surgery to disease sites receiving study drug injections
• Other: No concurrent high-dose steroids; At least 4 weeks since experimental therapy; No concurrent other experimental drugs or therapy; No prior gene therapy using adenoviral vectors

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%
• Life expectancy: Greater than 12 weeks
• Hematopoietic: Platelet count at least 100,000/mm3; Absolute neutrophil count at least 2000/mm3
• Hepatic: Total bilirubin no greater than upper limit of normal (ULN); AST/SGOT and/or ALT/SGPT no greater than 1.5 times ULN; Alkaline phosphatase no greater than 5 times ULN
• Renal: Not specified
• Other: Not pregnant or nursing; Barrier contraception required during treatment; Negative for HIV 1, HIV 2, hepatitis B, and hepatitis C; At least 2 years since prior malignancy, other than SSCHN; No contact with former tissue or organ transplant recipients or persons with severe immunodeficiency disease within 28 days following final dose of study drug; No serious concurrent medical conditions; No active uncontrolled infection

California
      Sidney Kimmel Cancer Center, San Diego,  California,  92121,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80262,  United States
Connecticut
      University of Connecticut School of Medicine, Farmington,  Connecticut,  06032,  United States
Illinois
      Clinical Sciences Building, Chicago,  Illinois,  60612,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Louisiana
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
Texas
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States

Study chairs or principal investigators

Lyndah Dreiling,  Study Chair,  Aventis Pharmaceuticals   

Study ID Numbers:  CDR0000066148; AVENTIS-T-202; NCI-V98-1394; MCC-11653; RP-T-202
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003257
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08