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

Official Title: “A Phase 2, Open-label Trial of the Safety and Biological Effect of Subcutaneous IRX-2 (With Cyclophosphamide, Indomethacin, and Zinc) in Patients With Resectable Cancer of the Head and Neck”

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.

Intervention(s) in this Clinical Trial

• 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
• Drug: Zinc
  • 21 days of zinc gluconate (65 mg) as part of an oral multivitamin
• Drug: Omeprazole
  • 21 days of 20 mg. orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: IRX-2 Regimen
  • The IRX-2 regimen 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.

Primary Measures

• Safety
  • Time Frame: Enrollment through 30 days post-surgery
    Safety Issue?: Yes

Secondary Measures

• Clinical and Histological Tumor Responses
  • Time Frame: At approx. 21 days, prior to surgery
    Safety Issue?: No
• Evaluate Patient Tolerance of Surgery and Post-operative Adjuvant Therapy;
  • Time Frame: Following surgery and post-operative therapy
    Safety Issue?: No
• Immune Competence as Measured by Lymphocyte Infiltration
  • Time Frame: At approx. 21 days, prior to surgery
    Safety Issue?: No
• Disease-free Survival
  • Time Frame: Time from cyclophosphamide administration and time from surgery to death or confirmed recurrent or progressive disease
    Safety Issue?: No
• Overall Survival
  • Time Frame: Time from cyclophosphamide administration and time from surgery to death or confirmed recurrent or progressive disease
    Safety Issue?: No
• 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
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: IRX Therapeutics Industry

Overall Clinical Trial Officials and Contacts

Jeffrey S. Moyer, MD Principal Investigator University of Michigan Hospitals  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00210470

Study ID Number: IRX-2 2005-A

ClinicalTrials.gov Identifier: NCT00210470

Health Authority: United States: Food and Drug Administration

IRX Therapeutics website