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

    Phase 2
  • Study Type

  • Study Participants

This was a Phase 2a trial to investigate the safety and biological activity of the RIX-2 Regimen in patients with untreated, resectable squamous cell cancer of the head and neck (HNSCC).
IRX-2 is a primary cell-derived biologic that reduces the immune suppression that is often seen in the cancer tumor micro-environment, restores immune function and activates a coordinated immune response against the tumor. IRX-2 is a complex proprietary therapeutic containing numerous active cytokine components, which restores and activates multiple immune cell types including T cells, dendritic cells, and natural killer cells to recognize and destroy tumors.

The present study administered the IRX-2 Regimen to 27 patients as a neoadjuvant (before surgery) therapy, and the main objective of the study was to determine the safety and tolerability of the IRX-2 regimen.
Study Started
Jul 31
Primary Completion
Dec 31
Study Completion
Mar 31
Results Posted
Feb 08
Last Update
Dec 11

Biological IRX-2

IRX-2 for 10 days (2 s.c. injections of 1 mL each day) into bilateral mastoid insertion regions.

Drug Cyclophosphamide

Single i.v. injection of low-dose (300 mg/m2) on Day 1

  • Other names: Cytoxan, cyclophosphane

Drug Indomethacin

21 days of oral indomethacin, 25 mg. 3 times daily

  • Other names: Indocin, Indocid

Drug Zinc

21 days of zinc gluconate (65 mg) as part of an oral multivitamin

  • Other names: zinc gluconate

Drug Omeprazole

21 days of 20 mg. orally

  • Other names: Prilosec

IRX-2 Regimen Experimental

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, zinc supplementation, and omeprazole.


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


IRX-2 Regimen

All Events

Event Type Organ System Event Term IRX-2 Regimen

Number of Participants With Adverse Events and Serious Adverse Events

The frequency of all Adverse Events (greater than 5%) is reported. All Serious Adverse Events were described.

IRX-2 Regimen

Additional AE Categories w lower frequency

Adverse Event: Anaemia

Adverse Event: Constipation

Adverse Event: Contusion

Adverse Event: Dizziness

Adverse Event: Dry Mouth

Adverse Event: Fatigue

Adverse Event: Headache

Adverse Event: Injection Site Discomfort

Adverse Event: Injection Site Pain

Adverse Event: Myalgia

Adverse Event: Nausea

Adverse Event: Pneumonia Aspiration

Adverse Event: Vomiting

Serious Adverse Events

Disease-free Survival

Estimate disease-free survival (DFS) (time from surgery to death or clinically apparent, biopsy confirmed recurrent or progressive disease after the completion of initial therapy, assessed up to 3 years; margins of resection positive for tumor will not be considered disease recurrence).

IRX-2 Regimen

1-year disease free survival probability

DFS Probability

2-year disease free survival probability

DFS Probability

3-year disease free survival probability

DFS Probability

Clinical and Histological Tumor Responses

Number of participants with the specified percent change in size of target lesion is presented

IRX-2 Regimen

0% to < 10%

-10% to < 0%

10% to < 20%

-20% to < -10%

20% to < 30%

>= 30%

Patient Tolerance of Surgery and Post-operative Adjuvant Therapy;

Patient Tolerance of Surgery and Post-operative Adjuvant Therapy as measured by median days spent in the hospital, intensive care unit, and step down unit.

IRX-2 Regimen

Median Days in hospital

days (Median)
Full Range: 1.0 to 39.0

Median Days in intensive care unit

days (Median)
Full Range: 0.0 to 17.0

Median Days in step-down unit

days (Median)
Full Range: 0.0 to 22.0

Immune Competence as Measured by Skin Test Reactivity

To assess measures of immune competence following administration of the IRX-2 regimen, including skin test reactivity.

IRX-2 Regimen

Induration at Day 21

Negative at Baseline and Positive at Day 21

Negative at both Baseline and Day 21 (%)

Positive at Baseline and Negative Day 21 (%)

Positive at both Baseline and at Day 21 (%)

Number of Participants With High Lymphocyte Infiltration (LI) According to the Visual Analog Scale (VAS)

Immunologic response features were extracted and quantified using a VAS of 0-100 mm to provide for a more continuous variable than the 0-4+ scale that is often used to assess histological responses. The scoring was such that 100 represented the maximum for any sample and 0 represented the lack of any parameter of interest. See publication of Berinstein, et al., 2012 for complete details.

IRX-2 Regimen

participants with high LI (>34 mm) VAS

Overall Survival

Estimate overall survival (OS) in patients receiving the IRX-2 regimen. IRX-2 is currently being studied in an on-going Phase 2b clinical trial in patients with newly diagnosed Stage II, III, and IVA squamous cell carcinoma of the oral cavity (INSPIRE)

IRX-2 Regimen

First Year (%)

percentage of subjects

Second Year (%)

percentage of subjects

Third Year (%)

percentage of subjects

Relationship Between Overall Survival (OS) and Immune Competence (Lymphocyte Infiltration, LI) in Participants With High LI and Low LI

After participants completed the IRX-2 regimen and the tumor resection was performed, tumor pathology was evaluated from tissue specimens obtained at tumor resection. Formalin-fixed, paraffin-embedded blocks, or unstained slides from the primary tumor were submitted to an independent pathology laboratory for hematoxylin and eosin staining, and evaluation of lymphocyte infiltration (LI). Participants were grouped into a "low LI" and "high LI" group based on the change in lymphocyte infiltration from the pretreatment tumor biopsy to the post-treatment tumor surgical resection. 5-year overall survival probabilities were then estimated (Kaplan-Meier) between the "low LI" and "high LI" groups

High Lymphocyte Infiltration (LI)

5-Year OS Probability

Low Lymphocyte Infiltration

5-Year OS Probability

Age, Continuous

years (Mean)
Standard Deviation: 9.4

Age, Categorical

Region of Enrollment

Sex: Female, Male

Overall Study

IRX-2 Regimen