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

Study Overview
=================
Brief Summary
-----------------
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).

Detailed Description
-----------------
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.

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

Conditions
-----------------
Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
-----------------
* Biological: IRX-2
* Drug: Cyclophosphamide
* Drug: Indomethacin
* Drug: Zinc
* Drug: Omeprazole


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label Single Arm Phase 2a trial of Safety of IRX-2 in Patients with Operable Head and Neck Cancer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IRX-2 Regimen<br>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. | Biological: IRX-2<br>* IRX-2 for 10 days (2 s.c. injections of 1 mL each day) into bilateral mastoid insertion regions.<br>Drug: Cyclophosphamide<br>* Single i.v. injection of low-dose (300 mg/m2) on Day 1<br>* Other names: cyclophosphane;Drug: Indomethacin<br>* 21 days of oral indomethacin, 25 mg. 3 times daily<br>* Other names: Indocid;Drug: Zinc<br>* 21 days of zinc gluconate (65 mg) as part of an oral multivitamin<br>* Other names: zinc gluconate;Drug: Omeprazole<br>* 21 days of 20 mg. orally<br>* Other names: Prilosec;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Enrollment through 30 days post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical and Histological Tumor Responses | Number of participants with the specified percent change in size of target lesion is presented | On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery | 
| 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. | Following surgery and post-operative therapy (up to 39 days post surgery) | 
| 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. | At approx. 21 days, prior to surgery | 
| 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). | 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 | 
| 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) | Time from surgery to death or confirmed recurrent or progressive disease, assessed up to 3 years | 
| 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. | On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery | 
| 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 | At time of surgery, after treatment with IRX-2 Regimen, assessed up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IRX-2, Head and Neck Cancer, Immunotherapy, Mouth Cancer, Throat Cancer