A Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in Treating Patients With Operable Head and Neck Cancer

• 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 designed to activate your own body's immune system so that it can better fight the invasion of head and neck cancer. In pre-clinical studies, IRX-2 has been shown to activate a number of different cells of the immune system.

IRX-2 was previously tested in a study of 13 patients with advanced head and neck cancer who had been previously treated and failed chemotherapy and/or radiation therapy. The trials were specifically designed to test the safety of IRX-2. Researchers found that IRX-2 did not appear to have major side effects. Also, the researchers believed that further study in less advanced head and neck cancer patients could be useful in obtaining more data on the safety of IRX-2 as well as data on possible effects on tumors and on patient survival.

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.

• Biological: IRX-2
  IRX-2 for 10 days (2 s.c. injections of 1 mL each day), 1 initial injection of cyclophosphamide, and 3 weeks of indomethacin (tablets or injection) and zinc supplementation (multivitamin tablet)
• Drug: Cyclophosphamide
  Single i.v. injection of low-dose (300 mg/m2) on Day 1
• Drug: Indomethacin
  21 days of oral indomethacin, 25 mg. 3 times daily
  Other Name: Indocin
• Drug: Zinc
  21 days of zinc gluconate (65 mg) as part of an oral multivitamin
  Other Name: zinc gluconate
• Drug: Omeprazole
  21 days of 20 mg. orally

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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