• Safety [ Time Frame: Enrollment through 30 days post-surgery ] [ Designated as safety issue: Yes ]
  The frequency of all Adverse Events (greater than 5%) is reported. All Serious Adverse Events were described. The number of deaths during study and their relatedness (or not) to treatment were reported. Changes in laboratory measures were reported. (See publication for details: Wolf, 2011)
  
  

• Clinical and Histological Tumor Responses [ Time Frame: At approx. 21 days, prior to surgery ] [ Designated as safety issue: No ]
  
• Evaluate Patient Tolerance of Surgery and Post-operative Adjuvant Therapy; [ Time Frame: Following surgery and post-operative therapy ] [ Designated as safety issue: No ]
  
• Immune Competence as Measured by Lymphocyte Infiltration [ Time Frame: At approx. 21 days, prior to surgery ] [ Designated as safety issue: No ]
  To assess measures of immune competence following administration of the IRX-2 regimen, including total lymphocyte count, peripheral T-cell count and subpopulation studies, and skin test reactivity
  
  
• Disease-free Survival [ Time Frame: Time from cyclophosphamide administration and time from surgery to death or confirmed recurrent or progressive disease ] [ Designated as safety issue: No ]
  Estimate disease-free survival (DFS) (defined as time from cyclophosphamide administration and time from surgery to death or clinically apparent, biopsy confirmed recurrent or progressive disease after the completion of initial therapy; margins of resection positive for tumor will not be considered disease recurrence)
  
  
• Overall Survival [ Time Frame: Time from cyclophosphamide administration and time from surgery to death or confirmed recurrent or progressive disease ] [ Designated as safety issue: No ]
  Estimate overall survival (OS) in patients receiving the IRX-2 regimen
  
  
• Correlation of Tumor Response or Immune Competence (Lymphocyte Infiltration) With Disease-Free Survival or Overall Survival [ Time Frame: Time from cyclophosphamide administration and time from surgery to death or confirmed recurrent or progressive disease ] [ Designated as safety issue: No ]
  Investigate whether clinical or histological tumor response or improvement in immune competence correlate with DFS and OS
  
  

IRX-2 is a biologic product that contains multiple cytokines produced under pharmaceutical standards from phytohemagglutinin (PHA) stimulated mononuclear cells obtained from normal healthy donors. The IRX-2 regimen is the combination of a 2-week course of IRX-2 itself, an initial low 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. Evaluation of clinical safety included regular clinical and laboratory evaluations. In the patients treated before surgery, evaluation of tumor response was undertaken by comparison of tumor size before and after the IRX-2 regimen. This study provided preliminary evidence of the safety and possible efficacy of IRX-2 in the pre-surgical, neoadjuvant treatment of HN SCC. The regimen was well tolerated in most patients, and histological and clinical tumor responses were observed.

The current study utilizes the same IRX-2 regimen evaluated in a more recent 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.