Back to resultsA Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in Treating Patients With Operable Head and Neck Cancer
Primary Purpose
Squamous Cell Carcinoma of the Head and Neck
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
IRX-2
Cyclophosphamide
Indomethacin
Zinc
Omeprazole
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Head and Neck Cancer, Immunotherapy, IRX-2, Mouth Cancer, Throat Cancer
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IRX-2 Regimen
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Clinical and Histological Tumor Responses
Number of participants with the specified percent change in size of target lesion is presented
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.
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.
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).
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)
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.
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
Full Information
NCT ID
NCT00210470
First Posted
September 13, 2005
Last Updated
December 10, 2020
Sponsor
Brooklyn ImmunoTherapeutics, LLC
1. Study Identification
Unique Protocol Identification Number
NCT00210470
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brooklyn ImmunoTherapeutics, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck
Keywords
Head and Neck Cancer, Immunotherapy, IRX-2, Mouth Cancer, Throat Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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
Allocation
N/A
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IRX-2 Regimen
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
IRX-2
Intervention Description
IRX-2 for 10 days (2 s.c. injections of 1 mL each day) into bilateral mastoid insertion regions.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan, cyclophosphane
Intervention Description
Single i.v. injection of low-dose (300 mg/m2) on Day 1
Intervention Type
Drug
Intervention Name(s)
Indomethacin
Other Intervention Name(s)
Indocin, Indocid
Intervention Description
21 days of oral indomethacin, 25 mg. 3 times daily
Intervention Type
Drug
Intervention Name(s)
Zinc
Other Intervention Name(s)
zinc gluconate
Intervention Description
21 days of zinc gluconate (65 mg) as part of an oral multivitamin
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Other Intervention Name(s)
Prilosec
Intervention Description
21 days of 20 mg. orally
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events and Serious Adverse Events
Description
The frequency of all Adverse Events (greater than 5%) is reported. All Serious Adverse Events were described.
Time Frame
Enrollment through 30 days post-surgery
Secondary Outcome Measure Information:
Title
Clinical and Histological Tumor Responses
Description
Number of participants with the specified percent change in size of target lesion is presented
Time Frame
On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery
Title
Patient Tolerance of Surgery and Post-operative Adjuvant Therapy;
Description
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.
Time Frame
Following surgery and post-operative therapy (up to 39 days post surgery)
Title
Immune Competence as Measured by Skin Test Reactivity
Description
To assess measures of immune competence following administration of the IRX-2 regimen, including skin test reactivity.
Time Frame
At approx. 21 days, prior to surgery
Title
Disease-free Survival
Description
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 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
Title
Overall Survival
Description
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 Frame
Time from surgery to death or confirmed recurrent or progressive disease, assessed up to 3 years
Title
Number of Participants With High Lymphocyte Infiltration (LI) According to the Visual Analog Scale (VAS)
Description
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.
Time Frame
On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery
Title
Relationship Between Overall Survival (OS) and Immune Competence (Lymphocyte Infiltration, LI) in Participants With High LI and Low LI
Description
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
Time Frame
At time of surgery, after treatment with IRX-2 Regimen, assessed up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey S. Moyer, MD
Organizational Affiliation
University of Michigan Hospitals
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21915712
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.
Results Reference
background
PubMed Identifier
21181158
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.
Results Reference
background
PubMed Identifier
20708999
Citation
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.
Results Reference
background
PubMed Identifier
20536465
Citation
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.
Results Reference
background
PubMed Identifier
19680453
Citation
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.
Results Reference
background
PubMed Identifier
19180118
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.
Results Reference
background
PubMed Identifier
18041679
Citation
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.
Results Reference
background
PubMed Identifier
17667526
Citation
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.
Results Reference
background
PubMed Identifier
17600288
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.
Results Reference
background
PubMed Identifier
17567942
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.
Results Reference
background
PubMed Identifier
15538546
Citation
Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):587-612.
Results Reference
background
PubMed Identifier
12860163
Citation
Hadden JW. Immunodeficiency and cancer: prospects for correction. Int Immunopharmacol. 2003 Aug;3(8):1061-71. doi: 10.1016/S1567-5769(03)00060-2.
Results Reference
background
PubMed Identifier
20539208
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.
Results Reference
result
PubMed Identifier
21284052
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.
Results Reference
result
PubMed Identifier
22057678
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.
Results Reference
result
PubMed Identifier
22109700
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.
Results Reference
result
Links:
URL
http://www.irxtherapeutics.com
Description
IRX Therapeutics website
Learn more about this trial
A Phase 2 Clinical Trial of the Safety and Effects of IRX-2 in Treating Patients With Operable Head and Neck Cancer
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