RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy followed by porfiromycin is more effective than radiation therapy alone in treating patients with head and neck cancer.

PURPOSE: Randomized double-blinded phase III trial to determine the effectiveness of radiation therapy followed by porfiromycin in treating patients with stage III or stage IV head and neck cancer.

Condition	Treatment or Intervention	Phase
stage IV squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx stage III squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the hypopharynx	Drug: porfiromycin	Phase III

Further Study Details: 

OBJECTIVES: I. Determine the time to tumor progression in patients with stage III or IV (without distant metastases) head and neck cancer treated with porfiromycin as adjuvant therapy to radiotherapy.

II. Determine percentage of patients with locoregional tumor recurrence at 2 years posttreatment.

III. Determine response rate, disease free survival time, and overall survival time in these patients.

IV. Evaluate the safety and tolerance of porfiromycin in these patients.

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are stratified according to primary tumor site (oral vs pharynx vs larynx) and disease stage (both T and N stage: T1-2 vs T3-4 and N0 vs N1-2 vs N3).

All patients are randomized to receive either porfiromycin (arm I) or placebo (arm II) as adjuvant therapy to radiation therapy.

Both arms follow the same treatment schedule. Daily radiation therapy commences on day 1. Patients receive porfiromycin or placebo by intravenous infusion over 30-60 minutes on day 5 and then on day 46 or 47. Porfiromycin or placebo is administered 30 minutes to 2 hours following radiation therapy.

All patients with N3 neck disease (metastases in a lymph node more than 6 cm in greatest dimension) undergo a planned neck dissection following external beam radiation at 4 to 12 weeks following therapy. This surgery is not needed for patients with N3 neck disease who do not have residual disease following radiotherapy.

Patients are followed at 4 weeks, then every 2 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A maximum of 530 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed stage III or IV squamous cell (epidermoid) carcinoma of head and neck limited to the oral cavity, oropharynx, hypopharynx, or larynx
• No distant metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for head and neck cancer
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy for head and neck cancer
• Surgery: No prior surgery (other than biopsy) for head and neck cancer

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: At least 6 months
• Hematopoietic: Granulocyte count at least 1,500/mm3; Platelet count at least 75,000/mm3; No known bleeding disorder
• Hepatic: Bilirubin no greater than 2 times normal; No end stage liver disease; PT and PTT no greater than 1.5 times normal
• Renal: Creatinine less than 2 times normal; No end stage renal disease
• Cardiovascular: No unstable angina
• Pulmonary: No severe oxygen dependent chronic obstructive pulmonary disease
• Other: No other malignancy known to be active within the past 5 years except basal or squamous cell skin cancer outside the planned radiation portals or carcinoma in situ of the cervix; No other life threatening illness; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

District of Columbia
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States
Illinois
      Health Advance Institute, Peoria,  Illinois,  61655-1466,  United States
Texas
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
Wisconsin
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States

Study chairs or principal investigators

Peter M. Glassman,  Study Chair,  Boehringer Ingelheim Pharmaceuticals   

Study ID Numbers:  CDR0000066281; BOEH-PORF-96-001; NCI-V98-1416; BOEH-BI-1164.1; COVANCE-1403; VION-PORF-96-001
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003328
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08