RATIONALE: Inserting the p53 gene into a person's cancer cells may improve the body's ability to fight cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy and radiation therapy with the p53 gene may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of gene therapy plus surgery followed by cisplatin and radiation therapy in treating patients who have newly diagnosed resectable stage III or stage IV cancer of the mouth or throat.

Condition	Treatment or Intervention	Phase
Hypopharyngeal Cancer Laryngeal Cancer lip and oral cavity cancer Oropharyngeal Cancer	Drug: Ad5CMV-p53 gene  Drug: cisplatin  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: gene therapy  Procedure: radiation therapy  Procedure: surgery	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the feasibility of treating patients with newly diagnosed resectable stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx with surgery and Ad5CMV-p53 gene followed by cisplatin and radiotherapy.
• Determine the progression-free survival, local control, and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in this patient population.

OUTLINE: This is a multicenter study.

Patients undergo surgical resection and receive an intraoperative Ad5CMV-p53 gene injection into the resection bed and into the deep soft tissue bed of the cervical level with nodal metastasis. Patients also receive a third intraoperative Ad5CMV-p53 gene injection into the neck dissection bed, where it is allowed to sit in place for 10 minutes.

Within 48-72 hours after surgery, patients receive a postoperative Ad5CMV-p53 gene injection into each of two drainage catheters next to the mucosal suture line and neck dissection bed, where it is allowed to sit in place for 2 hours.

Within 56 days after surgery, patients receive cisplatin IV over 30-90 minutes on days 1, 22, and 43 and radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients may receive 3 additional days of radiotherapy to high-risk areas on days 43-45.

Patients are followed every 2 months for 5 years. In the event of disease progression, patients are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed high-risk/limited stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx
• Newly diagnosed
• Previously untreated
• Considered surgically resectable
• Evidence of regional lymph node metastases (N1-N3)
• No distant metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3
• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT or SGPT no greater than 3 times ULN
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal:

• Creatinine no greater than 2 times ULN
• Creatinine clearance at least 60 mL/min

Other:

• Magnesium normal (magnesium supplement allowed)
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission
• HIV negative
• Not pregnant or nursing
• Patients must use effective barrier contraception and prevent bodily fluid transmission during and for 28 days after Ad5CMV-p53 gene administration

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• No concurrent intensity-modulated radiotherapy

Surgery:

• Not specified

Arizona
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States; Recruiting
Arkansas
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States; Recruiting
Colorado
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States; Recruiting
Florida
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Hines, Hines,  Illinois,  60141,  United States; Recruiting
Kansas
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160,  United States; Recruiting
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0293,  United States; Recruiting
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States; Recruiting
Louisiana
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201,  United States; Recruiting
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States; Recruiting
Mississippi
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States; Recruiting
New Mexico
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States; Recruiting
New York
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0502,  United States; Recruiting
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States; Recruiting
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Oregon
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States; Recruiting
South Carolina
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States; Recruiting
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States; Recruiting
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States; Recruiting
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States; Recruiting
Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112-5550,  United States; Recruiting
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States; Recruiting
Washington
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States; Recruiting

Study chairs or principal investigators

George H. Yoo, MD,  Study Chair,  Barbara Ann Karmanos Cancer Institute   

Study ID Numbers:  CDR0000068658; SWOG-S0011; NCT00017173
Record last reviewed:  February 2005
Last Updated:  April 4, 2005
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017173
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08