Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IRX-2 | Biological | IRX-2 for 10 days (2 s.c. injections of 1 mL each day) into bilateral mastoid insertion regions. |
|
| 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 |
| 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; |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jeffrey S. Moyer, MD | University of Michigan Hospitals | Principal Investigator |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21915712 | Background | 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. | |
| 21181158 | Background | 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. |
| Label | URL |
|---|---|
| IRX Therapeutics website | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Pathologically confirmed (by 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.
No medical contraindications to surgical resection and reconstruction required.
The first subject was enrolled July 2005 and the last subject visit was August 2009.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 and zinc supplementation. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 and zinc supplementation. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 27 participants were entered into study and treated. All participants were included in the safety analysis. | Posted | Count of Participants | Participants | Enrollment through 30 days post-surgery |
|
|
Primarily from the administration of cyclophosphamide to the time of surgery, except for Serious Adverse Events (reported up to 30 days after last dose of study medication)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 and zinc supplementation. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ASPIRATION PNEUMONIA | Infections and infestations | MedDRA (8.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CONSTIPATION | Gastrointestinal disorders | MedDRA (8.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gregory T. Wolf | University of Michigan Hospital | gregwolf@umich.edu |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D006258 | Head and Neck Neoplasms |
| D009062 | Mouth Neoplasms |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| C114857 | IRX 2 |
| D003520 | Cyclophosphamide |
| D007213 | Indomethacin |
| D015032 | Zinc |
| C030691 | gluconic acid |
| D009853 | Omeprazole |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
Not provided
Not provided
Open Label Single Arm Phase 2a trial of Safety of IRX-2 in Patients with Operable Head and Neck Cancer
Not provided
Not provided
Open Label
Not provided
| Cyclophosphamide | Drug | Single i.v. injection of low-dose (300 mg/m2) on Day 1 |
|
|
| Indomethacin | Drug | 21 days of oral indomethacin, 25 mg. 3 times daily |
|
|
| Zinc | Drug | 21 days of zinc gluconate (65 mg) as part of an oral multivitamin |
|
|
| Omeprazole | Drug | 21 days of 20 mg. orally |
|
|
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 |
| 20708999 | Background | 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. |
| 20536465 | Background | 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. |
| 19680453 | Background | 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. |
| 19180118 | Background | 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. |
| 18041679 | Background | 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. |
| 17667526 | Background | 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. |
| 17600288 | Background | 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. |
| 17567942 | Background | 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. |
| 15538546 | Background | Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2004 Sep;26(7):587-612. |
| 12860163 | Background | Hadden JW. Immunodeficiency and cancer: prospects for correction. Int Immunopharmacol. 2003 Aug;3(8):1061-71. doi: 10.1016/S1567-5769(03)00060-2. |
| 20539208 | Result | 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. |
| 21284052 | Result | 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. |
| 22057678 | Result | 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. |
| 22109700 | Result | 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. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Clinical and Histological Tumor Responses | Number of participants with the specified percent change in size of target lesion is presented | A total of 23 subjects who received the IRX-2 regimen were evaluated for tumor response based on the RECIST criteria | Posted | Count of Participants | Participants | On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery |
|
|
|
|
| Secondary | 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 the median days spent in the hospital, intensive care unit and step down unit was determined for 26 subjects | Posted | Median | Full Range | days | Following surgery and post-operative therapy (up to 39 days post surgery) |
|
|
|
| Secondary | 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. | Skin response (erythema) was evaluated at Baseline and Day 21 on 26 subjects treated with IRX-2 Regimen | Posted | Count of Participants | Participants | At approx. 21 days, prior to surgery |
|
|
|
| Secondary | 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). | Posted | Number | DFS Probability | 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 |
|
|
|
| Secondary | 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) | Posted | Number | percentage of subjects | Time from surgery to death or confirmed recurrent or progressive disease, assessed up to 3 years |
|
|
|
| Secondary | 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. | Number of patients with high lymphocyte infiltration (LI). | Posted | Number | participants with high LI (>34 mm) VAS | On approximately Day 21 (last day of treatment) prior to undergoing post-treatment surgery |
|
|
|
| Secondary | 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 | Posted | Number | 5-Year OS Probability | At time of surgery, after treatment with IRX-2 Regimen, assessed up to 5 years |
|
|
|
| 10 |
| 27 |
| 7 |
| 27 |
| 23 |
| 27 |
| RESPIRATORY INFECTION | Respiratory, thoracic and mediastinal disorders | MedDRA (8.0) | Non-systematic Assessment | Respiratory Infection with Asthma |
|
| NECK ABSCESS | Infections and infestations | MedDRA (8.0) | Non-systematic Assessment |
|
| POSTOPERATIVE INFECTION | Infections and infestations | MedDRA (8.0) | Non-systematic Assessment |
|
| ALCOHOL WITHDRAWAL | General disorders | MedDRA (8.0) | Non-systematic Assessment |
|
| DIZZINESS | General disorders | MedDRA (8.0) | Systematic Assessment |
|
| FATIGUE | General disorders | MedDRA (8.0) | Systematic Assessment |
|
| HEADACHE | General disorders | MedDRA (8.0) | Systematic Assessment |
|
| INJECTION SITE PAIN | General disorders | MedDRA (8.0) | Systematic Assessment |
|
| NAUSEA | General disorders | MedDRA (8.0) | Systematic Assessment |
|
| PNEUMONIA ASPIRATION | Respiratory, thoracic and mediastinal disorders | MedDRA (8.0) | Systematic Assessment |
|
| DRY MOUTH | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| CONTUSION | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (8.0) | Systematic Assessment |
|
| INJECTION SITE DISCOMFORT | General disorders | MedDRA (8.0) | Systematic Assessment |
|
Not provided
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D028561 | Transition Elements |
| D008670 | Metals |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001562 | Benzimidazoles |
| Title | Measurements |
|---|---|
|
| 10% to < 20% |
|
| 20% to < 30% |
|
| >= 30% |
|
|
| Title | Measurements |
|---|---|
|
| Negative at Baseline and Positive at Day 21 |
|
| Induration at Day 21 |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|