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

• ClinicalTrials.gov Identifier: NCT00210470
• Recruitment Status: Completed
• First Posted: September 21, 2005
• Results First Posted: February 8, 2012
• Last Update Posted: December 11, 2020
• Sponsor: Brooklyn ImmunoTherapeutics, LLC
• Information provided by (Responsible Party): Brooklyn ImmunoTherapeutics, LLC

Tracking Information

• First Submitted Date: September 13, 2005
• First Posted Date: September 21, 2005
• Results First Submitted Date: January 6, 2012
• Results First Posted Date: February 8, 2012
• Last Update Posted Date: December 11, 2020
• Study Start Date: July 2005
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2020)

Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: Enrollment through 30 days post-surgery ]

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

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: December 10, 2020)

• Clinical and Histological Tumor Responses [ Time Frame: On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery ]
  Number of participants with the specified percent change in size of target lesion is presented
• Patient Tolerance of Surgery and Post-operative Adjuvant Therapy; [ Time Frame: Following surgery and post-operative therapy (up to 39 days post surgery) ]
  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.
• Immune Competence as Measured by Skin Test Reactivity [ Time Frame: At approx. 21 days, prior to surgery ]
  To assess measures of immune competence following administration of the IRX-2 regimen, including skin test reactivity.
• Disease-free Survival [ Time Frame: 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 ]
  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).
• Overall Survival [ Time Frame: Time from surgery to death or confirmed recurrent or progressive disease, assessed up to 3 years ]
  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)
• Number of Participants With High Lymphocyte Infiltration (LI) According to the Visual Analog Scale (VAS) [ Time Frame: On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery ]
  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.
• Relationship Between Overall Survival (OS) and Immune Competence (Lymphocyte Infiltration, LI) in Participants With High LI and Low LI [ Time Frame: At time of surgery, after treatment with IRX-2 Regimen, assessed up to 5 years ]
  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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Masking Description:

Open Label

Primary Purpose: Treatment

• Condition: Squamous Cell Carcinoma of the Head and Neck

Intervention

• 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 Name: zinc gluconate
• Drug: Omeprazole
  21 days of 20 mg. orally
  Other Name: Prilosec

Study Arms

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, zinc supplementation, and omeprazole.

Interventions:

• Biological: IRX-2
• Drug: Cyclophosphamide
• Drug: Indomethacin
• Drug: Zinc
• Drug: Omeprazole

Publications *

• 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.
• 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.
• Naylor PH, Hernandez KE, Nixon AE, Brandwein HJ, Haas GP, Wang CY, Hadden JW. IRX-2 increases the T cell-specific immune response to protein/peptide vaccines. Vaccine. 2010 Oct 8;28(43):7054-62. doi: 10.1016/j.vaccine.2010.08.014. Epub 2010 Aug 13.
• Naylor PH, Hadden JW. Preclinical studies with IRX-2 and thymosin alpha1 in combination therapy. Ann N Y Acad Sci. 2010 Apr;1194:162-8. doi: 10.1111/j.1749-6632.2010.05475.x.
• Rapidis AD, Wolf GT. Immunotherapy of head and neck cancer: current and future considerations. J Oncol. 2009;2009:346345. doi: 10.1155/2009/346345. Epub 2009 Aug 9.
• 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.
• Bright J, Al-Shamahi A. BioPartnering Europe--15th Annual Conference. Highlights from open house and emerging company presentations--Part 1. IDrugs. 2007 Dec;10(12):855-7. No abstract available.
• Egan JE, Quadrini KJ, Santiago-Schwarz F, Hadden JW, Brandwein HJ, Signorelli KL. IRX-2, a novel in vivo immunotherapeutic, induces maturation and activation of human dendritic cells in vitro. J Immunother. 2007 Sep;30(6):624-33. doi: 10.1097/CJI.0b013e3180691593.
• 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.
• 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.
• Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):587-612.
• Hadden JW. Immunodeficiency and cancer: prospects for correction. Int Immunopharmacol. 2003 Aug;3(8):1061-71. doi: 10.1016/S1567-5769(03)00060-2.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 21, 2007): 27
• Original Enrollment (submitted: September 13, 2005): 25
• Actual Study Completion Date: March 2012
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT00210470
• Other Study ID Numbers: IRX-2 2005-A
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Brooklyn ImmunoTherapeutics, LLC
• Original Responsible Party: Not Provided
• Current Study Sponsor: Brooklyn ImmunoTherapeutics, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Brooklyn ImmunoTherapeutics, LLC
• Verification Date: December 2020