IRX-2 is a biologic product that contains multiple cytokines produced under pharmaceutical standards from phytohemagglutinin (PHA) stimulated mononuclear cells obtained from normal donors. The IRX-2 regimen to be studied is the combination of a 2-week course of IRX-2 itself, an initial dose of cyclophosphamide and a 3-week course of indomethacin and zinc supplementation.

The present study is based in large part on observations made during an exploratory Phase 1-2 study of the safety and efficacy of the IRX-2 regimen performed at the Instituto Nacional de Cancerologia (INCAN), Mexico's National Cancer Institute. Patients with head and neck (HN) squamous cell carcinoma (SCC) were treated with the IRX-2 regimen, some as neoadjuvant therapy prior to surgery and some for advanced disease. Three different doses and dose schedules were studied. In the patients treated preoperatively, evaluation of tumor response was undertaken by comparison of tumor size before and after the IRX-2 regimen. Histological specimens were also graded by percent increase in lymphocyte infiltration and by tumor cell reduction or fragmentation. Evaluation of clinical safety included regular clinical and laboratory evaluations.

This study provided preliminary evidence of the safety and likely efficacy of IRX-2 in the pre-surgical, neoadjuvant treatment of HN SCC. The regimen was well tolerated in most patients, histological and clinical tumor responses were observed and overall survival appeared to be improved compared to similar patients treated at INCAN.

The current study utilizes the same IRX-2 regimen recently evaluated in a Phase 1 trial in patients with recurrent, refractory HN SCC performed at INCAN and the University of Kentucky, where the safety of the IRX-2 regimen was studied and some evidence of clinical activity was observed in 2 of 10 refractory patients.

The current study in patients with newly diagnosed, resectable HN SCC is being conducted to confirm the safety and biological effect of the IRX-2 regimen in a multi-institutional study in the same population to be studied in a planned randomized Phase 3 trial. The primary focus will be on observations made from the start of treatment through the planned surgical resection of the primary tumor.

Inclusion Criteria:

• Pathologically confirmed (histology) Squamous Cell Carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx.
• No prior surgery, radiation therapy or chemotherapy of this tumor other than biopsy or emergency procedure required for supportive care.
• Clinically staged Stage II, III, or IVA cancer, assessed to be surgically resectable with curative intent.
• Life Expectancy of greater than 6 months

Exclusion Criteria:

• Stage IVB Squamous Cell Carcinoma
• Use of any investigational agent within the previous 30 days
• Uncontrolled cardiovascular disease
• Myocardial infarction within the last 3 months
• Abnormal hemoglobin, neutrophil, lymphocyte or platelet counts
• Positive for hepatitis B or C or HIV
• Evidence of distant metastases
• Clinical gastritis or peptic ulcer within the last 6 months
• Stroke within the last six months