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

Sponsor
Brooklyn ImmunoTherapeutics, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00210470
Collaborator
(none)
27
Enrollment
1
Arm
80
Duration (Months)

Study Details

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
27 participants
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 CancerOpen 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
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 Start Date :
Jul 1, 2005
Actual Primary Completion Date :
Dec 1, 2010
Actual Study Completion Date :
Mar 1, 2012

Arms and Interventions

Arm Intervention/Treatment
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.

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 Names:
  • zinc gluconate

    • Drug: Omeprazole
    21 days of 20 mg. orally
    Other Names:
  • Prilosec

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events and Serious Adverse Events [Enrollment through 30 days post-surgery]

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

    Secondary Outcome Measures

    1. Clinical and Histological Tumor Responses [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

    2. Patient Tolerance of Surgery and Post-operative Adjuvant Therapy; [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.

    3. Immune Competence as Measured by Skin Test Reactivity [At approx. 21 days, prior to surgery]

      To assess measures of immune competence following administration of the IRX-2 regimen, including skin test reactivity.

    4. Disease-free Survival [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).

    5. Overall Survival [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)

    6. Number of Participants With High Lymphocyte Infiltration (LI) According to the Visual Analog Scale (VAS) [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.

    7. Relationship Between Overall Survival (OS) and Immune Competence (Lymphocyte Infiltration, LI) in Participants With High LI and Low LI [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Brooklyn ImmunoTherapeutics, LLC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Brooklyn ImmunoTherapeutics, LLC
    ClinicalTrials.gov Identifier:
    NCT00210470
    Other Study ID Numbers:
    • IRX-2 2005-A
    First Posted:
    Sep 21, 2005
    Last Update Posted:
    Dec 11, 2020
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Brooklyn ImmunoTherapeutics, LLC
    Head and Neck Cancer
    Immunotherapy
    IRX-2
    Mouth Cancer
    Throat Cancer
    Additional relevant MeSH terms:
    Squamous Cell Carcinoma of Head and Neck
    Zinc
    Indomethacin
    Cyclophosphamide
    Omeprazole

    Study Results

    Participant Flow

    Recruitment Details The first subject was enrolled July 2005 and the last subject visit was August 2009.
    Pre-assignment Detail 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.
    Arm/Group Title IRX-2 Regimen
    Arm/Group 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 and zinc supplementation.
    Period Title: Overall Study
    STARTED 27
    COMPLETED 27
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title IRX-2 Regimen
    Arm/Group 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 and zinc supplementation.
    Overall Participants 27
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    24
    88.9%
    >=65 years
    3
    11.1%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.4
    (9.4)
    Sex: Female, Male (Count of Participants)
    Female
    7
    25.9%
    Male
    20
    74.1%
    Region of Enrollment (participants) [Number]
    United States
    26
    96.3%
    Mexico
    1
    3.7%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    27 participants were entered into study and treated. All participants were included in the safety analysis.
    Arm/Group Title IRX-2 Regimen
    Arm/Group Description A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation
    Measure Participants 27
    Adverse Event: Injection Site Pain
    6
    22.2%
    Adverse Event: Headache
    8
    29.6%
    Adverse Event: Nausea
    6
    22.2%
    Adverse Event: Constipation
    4
    14.8%
    Adverse Event: Dizziness
    4
    14.8%
    Adverse Event: Fatigue
    3
    11.1%
    Adverse Event: Pneumonia Aspiration
    3
    11.1%
    Adverse Event: Anaemia
    3
    11.1%
    Adverse Event: Injection Site Discomfort
    3
    11.1%
    Adverse Event: Myalgia
    2
    7.4%
    Adverse Event: Contusion
    2
    7.4%
    Adverse Event: Dry Mouth
    2
    7.4%
    Adverse Event: Vomiting
    2
    7.4%
    Additional AE Categories w lower frequency
    4
    14.8%
    Serious Adverse Events
    7
    25.9%
    2. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    A total of 23 subjects who received the IRX-2 regimen were evaluated for tumor response based on the RECIST criteria
    Arm/Group Title IRX-2 Regimen
    Arm/Group Description A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation
    Measure Participants 23
    -20% to < -10%
    4
    14.8%
    -10% to < 0%
    7
    25.9%
    0% to < 10%
    9
    33.3%
    10% to < 20%
    1
    3.7%
    20% to < 30%
    0
    0%
    >= 30%
    2
    7.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection IRX-2 Regimen
    Comments
    Type of Statistical Test Equivalence
    Comments The correlation of each of the above variables at biopsy/Day 1, surgery/Day 21, and change with percent change in the longest diameter (LD) of the primary tumor was calculated using Spearman rank correlations (183 correlations). Due to outliers in the distribution of percent change in the longest diameter, it was felt that the Spearman rank correlations would be more appropriate than Pearson correlations.
    Statistical Test of Hypothesis p-Value <0.10
    Comments
    Method Spearman Rank
    Comments
    3. Secondary Outcome
    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)

    Outcome Measure Data

    Analysis Population Description
    Following surgery the median days spent in the hospital, intensive care unit and step down unit was determined for 26 subjects
    Arm/Group Title IRX-2 Regimen
    Arm/Group Description A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation
    Measure Participants 26
    Median Days in hospital
    8.5
    Median Days in intensive care unit
    0.5
    Median Days in step-down unit
    0.5
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Skin response (erythema) was evaluated at Baseline and Day 21 on 26 subjects treated with IRX-2 Regimen
    Arm/Group Title IRX-2 Regimen
    Arm/Group Description A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation
    Measure Participants 26
    Positive at both Baseline and at Day 21 (%)
    12
    44.4%
    Negative at both Baseline and Day 21 (%)
    6
    22.2%
    Positive at Baseline and Negative Day 21 (%)
    6
    22.2%
    Negative at Baseline and Positive at Day 21
    2
    7.4%
    Induration at Day 21
    3
    11.1%
    5. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title IRX-2 Regimen
    Arm/Group Description A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation
    Measure Participants 26
    1-year disease free survival probability
    0.721
    2-year disease free survival probability
    0.641
    3-year disease free survival probability
    0.620
    6. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title IRX-2 Regimen
    Arm/Group Description A 2-week course of IRX-2, an initial low dose of cyclophosphamide, and a 3-week course of indomethacin and zinc supplementation
    Measure Participants 26
    First Year (%)
    92
    Second Year (%)
    73
    Third Year (%)
    69
    7. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Number of patients with high lymphocyte infiltration (LI).
    Arm/Group Title IRX-2 Regimen
    Arm/Group 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 and zinc supplementation.
    Measure Participants 25
    Number [participants with high LI (>34 mm) VAS]
    18
    66.7%
    8. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title High Lymphocyte Infiltration (LI) Low Lymphocyte Infiltration
    Arm/Group Description Participants with high lymphocyte infiltration after treatment with the IRX-2 regimen Participants with low lymphocyte infiltration after treatment with the IRX-2 regimen
    Measure Participants 13 12
    Number [5-Year OS Probability]
    0.80
    0.50

    Adverse Events

    Time Frame 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)
    Adverse Event Reporting Description
    Arm/Group Title IRX-2 Regimen
    Arm/Group 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 and zinc supplementation.
    All Cause Mortality
    IRX-2 Regimen
    Affected / at Risk (%) # Events
    Total 10/27 (37%)
    Serious Adverse Events
    IRX-2 Regimen
    Affected / at Risk (%) # Events
    Total 7/27 (25.9%)
    General disorders
    ALCOHOL WITHDRAWAL 1/27 (3.7%) 1
    Infections and infestations
    ASPIRATION PNEUMONIA 3/27 (11.1%) 3
    NECK ABSCESS 1/27 (3.7%) 1
    POSTOPERATIVE INFECTION 1/27 (3.7%) 1
    Respiratory, thoracic and mediastinal disorders
    RESPIRATORY INFECTION 1/27 (3.7%) 2
    Other (Not Including Serious) Adverse Events
    IRX-2 Regimen
    Affected / at Risk (%) # Events
    Total 23/27 (85.2%)
    Blood and lymphatic system disorders
    ANAEMIA 3/27 (11.1%) 3
    Gastrointestinal disorders
    CONSTIPATION 4/27 (14.8%) 4
    DRY MOUTH 2/27 (7.4%) 2
    VOMITING 2/27 (7.4%) 2
    General disorders
    DIZZINESS 4/27 (14.8%) 4
    FATIGUE 3/27 (11.1%) 3
    HEADACHE 8/27 (29.6%) 8
    INJECTION SITE PAIN 6/27 (22.2%) 6
    NAUSEA 6/27 (22.2%) 6
    INJECTION SITE DISCOMFORT 2/27 (7.4%) 2
    Injury, poisoning and procedural complications
    CONTUSION 2/27 (7.4%) 2
    Musculoskeletal and connective tissue disorders
    MYALGIA 2/27 (7.4%) 2
    Respiratory, thoracic and mediastinal disorders
    PNEUMONIA ASPIRATION 3/27 (11.1%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Gregory T. Wolf
    Organization University of Michigan Hospital
    Phone
    Email gregwolf@umich.edu
    Responsible Party:
    Brooklyn ImmunoTherapeutics, LLC
    ClinicalTrials.gov Identifier:
    NCT00210470
    Other Study ID Numbers:
    • IRX-2 2005-A
    First Posted:
    Sep 21, 2005
    Last Update Posted:
    Dec 11, 2020
    Last Verified:
    Dec 1, 2020