Clinical trial NCT00210470: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Keywords: Head and Neck Cancer
Immunotherapy
IRX-2
Mouth Cancer
Throat Cancer
Lead sponsor: Brooklyn ImmunoTherapeutics, LLC
Sponsor class: INDUSTRY
First posted: 2005-09-21
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label Single Arm Phase 2a trial of Safety of IRX-2 in Patients with Operable Head and Neck Cancer
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: Enrollment through 30 days post-surgery
Secondary outcomes:
measure: Clinical and Histological Tumor Responses
timeFrame: On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery
measure: Patient Tolerance of Surgery and Post-operative Adjuvant Therapy;
timeFrame: Following surgery and post-operative therapy (up to 39 days post surgery)
measure: Immune Competence as Measured by Skin Test Reactivity
timeFrame: At approx. 21 days, prior to surgery
measure: Disease-free Survival
timeFrame: 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
measure: Overall Survival
timeFrame: Time from surgery to death or confirmed recurrent or progressive disease, assessed up to 3 years
measure: Number of Participants With High Lymphocyte Infiltration (LI) According to the Visual Analog Scale (VAS)
timeFrame: On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery
measure: Relationship Between Overall Survival (OS) and Immune Competence (Lymphocyte Infiltration, LI) in Participants With High LI and Low LI
timeFrame: At time of surgery, after treatment with IRX-2 Regimen, assessed up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: University of Michigan Hospitals
name: Jeffrey S. Moyer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schilling B, Harasymczuk M, Schuler P, Egan JE, Whiteside TL. IRX-2, a novel biologic, favors the expansion of T effector over T regulatory cells in a human tumor microenvironment model. J Mol Med (Berl). 2012 Feb;90(2):139-47. doi: 10.1007/s00109-011-0813-8. Epub 2011 Sep 14.
citation: Czystowska M, Szczepanski MJ, Szajnik M, Quadrini K, Brandwein H, Hadden JW, Whiteside TL. Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic. Cancer Immunol Immunother. 2011 Apr;60(4):495-506. doi: 10.1007/s00262-010-0951-9. Epub 2010 Dec 23.
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citation: Czystowska M, Han J, Szczepanski MJ, Szajnik M, Quadrini K, Brandwein H, Hadden JW, Signorelli K, Whiteside TL. IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death. Cell Death Differ. 2009 May;16(5):708-18. doi: 10.1038/cdd.2008.197. Epub 2009 Jan 30.
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citation: Hadden JW, Verastegui E, Hadden E. IRX-2 and thymosin alpha1 (Zadaxin) increase T lymphocytes in T lymphocytopenic mice and humans. Ann N Y Acad Sci. 2007 Sep;1112:245-55. doi: 10.1196/annals.1415.032. Epub 2007 Jun 28.
citation: Naylor PH, Quadrini K, Garaci E, Rasi G, Hadden JW. Immunopharmacology of thymosin alpha1 and cytokine synergy. Ann N Y Acad Sci. 2007 Sep;1112:235-44. doi: 10.1196/annals.1415.036. Epub 2007 Jun 13.
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citation: Freeman SM, Franco JL, Kenady DE, Baltzer L, Roth Z, Brandwein HJ, Hadden JW. A phase 1 safety study of an IRX-2 regimen in patients with squamous cell carcinoma of the head and neck. Am J Clin Oncol. 2011 Apr;34(2):173-8. doi: 10.1097/COC.0b013e3181dbb9d8.
citation: Wolf GT, Fee WE Jr, Dolan RW, Moyer JS, Kaplan MJ, Spring PM, Suen J, Kenady DE, Newman JG, Carroll WR, Gillespie MB, Freeman SM, Baltzer L, Kirkley TD, Brandwein HJ, Hadden JW. Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer. Head Neck. 2011 Dec;33(12):1666-74. doi: 10.1002/hed.21660. Epub 2011 Jan 31.
citation: Berinstein NL, Wolf GT, Naylor PH, Baltzer L, Egan JE, Brandwein HJ, Whiteside TL, Goldstein LC, El-Naggar A, Badoual C, Fridman WH, White JM, Hadden JW. Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen. Cancer Immunol Immunother. 2012 Jun;61(6):771-82. doi: 10.1007/s00262-011-1134-z. Epub 2011 Nov 6.
citation: Whiteside TL, Butterfield LH, Naylor PH, Egan JE, Hadden JW, Baltzer L, Wolf GT, Berinstein NL. A short course of neoadjuvant IRX-2 induces changes in peripheral blood lymphocyte subsets of patients with head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2012 Jun;61(6):783-8. doi: 10.1007/s00262-011-1136-x. Epub 2011 Nov 23.