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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
IRX Therapeutics
ClinicalTrials.gov Identifier:
NCT00210470
First received: September 13, 2005
Last updated: May 22, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck
Biological: IRX-2
Drug: Cyclophosphamide
Drug: Indomethacin
Drug: Zinc
Drug: Omeprazole
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by IRX Therapeutics:

Primary Outcome Measures:
  • Number of Participants With Adverse Events and Serious Adverse Events [ 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, as well as changes in laboratory measures, were published (see referenced publication for details: Wolf, 2011).


Secondary Outcome Measures:
  • 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


Enrollment: 27
Study Start Date: July 2005
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00210470

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Stanford Cancer Center
Stanford, California, United States, 94305-5826
United States, Iowa
University of Iowa Hospital & Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536
United States, Massachusetts
Lahey Clinic Medical Center
Burlington, Massachusetts, United States, 01805
United States, Michigan
University of Michigan Hospitals
Ann Arbor, Michigan, United States, 48109-0312
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
IRX Therapeutics
Investigators
Principal Investigator: Jeffrey S. Moyer, MD University of Michigan Hospitals
  More Information

Additional Information:
Publications:

Responsible Party: IRX Therapeutics
ClinicalTrials.gov Identifier: NCT00210470     History of Changes
Other Study ID Numbers: IRX-2 2005-A
Study First Received: September 13, 2005
Results First Received: January 6, 2012
Last Updated: May 22, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by IRX Therapeutics:
Head and Neck Cancer
Immunotherapy
IRX-2
Mouth Cancer
Throat Cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cyclophosphamide
Indomethacin
Omeprazole
Zinc
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Gout Suppressants
Tocolytic Agents
Reproductive Control Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on July 24, 2014