<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03758781</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-19491</org_study_id>
    <nct_id>NCT03758781</nct_id>
  </id_info>
  <brief_title>IRX-2 Regimen Combined With Nivolumab in Recurrent/Metastatic Solid Tumors</brief_title>
  <official_title>The IRX-2 Regimen Combined With Nivolumab in Recurrent/Metastatic Solid Tumors: A Phase 1b Study to Evaluate the Safety, Determine Recommended Phase 2 Dose (RP2D), and Investigate the Biologic and Clinical Activity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to determine the safety of IRX-2 Regimen combined with Nivolumab in patients&#xD;
      with recurrent metastatic solid tumors. Researchers believe that this combination will have a&#xD;
      tolerable safety profile and will increase the response rate in comparison to Nivolumab&#xD;
      alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The first phase of this trial is to establish the safety of IRX-2 Regimen combined with&#xD;
      Nivolumab. The IRX-2 Regimen is a 21-day regimen of cyclophosophamide on Day 1 and&#xD;
      subcutaneous IRX-2 injections for 10 days between Days 4 and 18. If no dose limiting&#xD;
      toxicities (DLTs) are observed during the first 4 weeks of treatment, the enrollment will&#xD;
      continue in a dose expansion phase. If there is a study treatment related DLT in 1 of 6&#xD;
      patients, the same dose will be investigated at the dose expansion cohorts. If study&#xD;
      treatment related DLT is observed in 2 of 6 patients, accrual will be stopped and new dose&#xD;
      levels or treatment sequences will be considered.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 13, 2019</start_date>
  <completion_date type="Actual">August 11, 2021</completion_date>
  <primary_completion_date type="Actual">February 21, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Experience Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>A DLT is defined as any Grade 3 or higher toxicity which occurs during the DLT evaluation period of 4 weeks (during Cycle 1 Day 1 and Cycle 1 Day 28) and considered related to study treatment. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Objective response determined using Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 and Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival of combination therapy</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Progression free survival defined as the time from Day 1 of treatment to evidence of progression. Progression will be defined by RECIST Version 1.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Metastatic Cancer</condition>
  <condition>Recurrent Cancer</condition>
  <condition>Solid Tumor</condition>
  <condition>Renal Cell Carcinoma</condition>
  <condition>Urothelial Carcinoma</condition>
  <condition>NSCLC</condition>
  <condition>Squamous Cell Carcinoma</condition>
  <condition>Non-Small Cell Lung Cancer</condition>
  <condition>Squamous Cell Carcinoma of the Head and Neck</condition>
  <arm_group>
    <arm_group_label>IRX-2 Regimen combined with Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IRX-2 Regimen (4 ml) combined with Nivolumab (240 mg)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IRX 2</intervention_name>
    <description>IRX-2 Regimen: 21 day regimen of cyclophosphamide on Day 1 and subcutaneous IRX-2 injections for 10 days between Days 4 and 18. This 21 day regimen will be given every 12 weeks.</description>
    <arm_group_label>IRX-2 Regimen combined with Nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab 240 mg will be given via IV infusion once every 2 weeks.</description>
    <arm_group_label>IRX-2 Regimen combined with Nivolumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
          -  Participants must have histologically or cytologically confirmed renal cell&#xD;
             carcinoma,urothelial carcinoma, non-small cell lung cancer, squamous cell carcinoma of&#xD;
             the head and neck or melanoma.&#xD;
&#xD;
          -  Participants must have recurrent or metastatic disease that is not amenable to local&#xD;
             therapy with curative intent (surgery or radiation therapy with or without&#xD;
             chemotherapy).&#xD;
&#xD;
          -  Must be willing and able to give informed consent and adhere to protocol therapy;&#xD;
             written informed consent and any locally required authorization must be obtained from&#xD;
             the participant prior to performing any protocol-related procedures, including&#xD;
             screening evaluations&#xD;
&#xD;
          -  Prior exposure to PD-1/PD-L1 inhibitor monotherapy, or prior exposure to CTLA-4&#xD;
             inhibitor monotherapy is allowed.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Adequate normal organ and marrow function&#xD;
&#xD;
          -  Participants who are receiving therapeutic anti-coagulant therapy are eligible.&#xD;
&#xD;
          -  Palliative radiation therapy is allowed to non-target lesions at the discretion of the&#xD;
             treating physician.&#xD;
&#xD;
          -  Participants must have measurable disease, defined as at least one lesion that can be&#xD;
             accurately measured in at least one dimension (longest diameter to be recorded) as&#xD;
             outlined in RECIST version 1.1.&#xD;
&#xD;
          -  Life expectancy of greater than 3 months.&#xD;
&#xD;
          -  Female participants of childbearing potential must have a negative serum pregnancy&#xD;
             test within 7 days prior to treatment.&#xD;
&#xD;
          -  Body weight must be greater than 66 pounds.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior exposure to a combination of IRX-2 regimen, PD-1/PD-L1 inhibitors and CTLA-4&#xD;
             inhibitors are excluded. Prior exposure to PD-1/PD-L1 inhibitors is allowed.&#xD;
&#xD;
          -  Radiation therapy with a curable intent within 30 days of first dose of study&#xD;
             treatment is excluded. However, radiation therapy with a palliative intent is allowed&#xD;
             to treat after 14 days from the last dose of radiation.&#xD;
&#xD;
          -  Any medical contraindications or previous therapy that would preclude treatment with&#xD;
             the IRX-2 Regimen, or nivolumab.&#xD;
&#xD;
          -  Any unresolved toxicity Grade 2 or greater from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria.&#xD;
&#xD;
          -  Participants with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
             treatment with IRX-2, or nivolumab may be included only after consultation with the&#xD;
             study physician.&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 14 days before the first&#xD;
             dose of study treatment. Some exceptions apply.&#xD;
&#xD;
          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of study treatment. Note: Local surgery of isolated lesions for palliative&#xD;
             intent is acceptable.&#xD;
&#xD;
          -  History of allogenic organ transplantation.&#xD;
&#xD;
          -  Symptomatic cardiopulmonary disease, coronary artery disease, serious arrhythmia or&#xD;
             chronic lung disease. Participants with these conditions who are stable with&#xD;
             relatively minor symptoms and who are appropriate candidates for systemic treatments&#xD;
             need not be excluded.&#xD;
&#xD;
          -  Myocardial infarction within the last 3 months.&#xD;
&#xD;
          -  Known infection with hepatitis B, hepatitis C, or HIV.&#xD;
&#xD;
          -  Signs or symptoms of systemic infection (use of antibiotics to treat superficial&#xD;
             infection or contamination of tumor shall not, by itself, be considered evidence of&#xD;
             infection).&#xD;
&#xD;
          -  Clinically significant gastritis or peptic ulcer disease&#xD;
&#xD;
          -  Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months.&#xD;
&#xD;
          -  Allergy to ciprofloxacin (or other quinolones).&#xD;
&#xD;
          -  Previous diagnosis of invasive cancer from which the individual is not disease-free&#xD;
             AND that has required treatment within the past 3 years, except for superficial skin,&#xD;
             cervical cancer in-situ, or early stage prostate or bladder cancer (i.e. treatment&#xD;
             with curative intent and long term disease-free expectations).&#xD;
&#xD;
          -  History of leptomeningeal carcinomatosis&#xD;
&#xD;
          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients.&#xD;
&#xD;
          -  Female participants who are pregnant or breastfeeding or male or female participants&#xD;
             of reproductive potential who are not willing to employ effective birth control from&#xD;
             screening to 1 year after the last dose of study treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rohit Jain, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://moffitt.org/clinical-trials-research/clinical-trials/</url>
    <description>Moffitt Cancer Center Clinical Trials Website</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03758781
org study id: MCC-19491
nct id: NCT03758781
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is to determine the safety of IRX-2 Regimen combined with Nivolumab in patients
      with recurrent metastatic solid tumors. Researchers believe that this combination will have a
      tolerable safety profile and will increase the response rate in comparison to Nivolumab
      alone.
The first phase of this trial is to establish the safety of IRX-2 Regimen combined with
      Nivolumab. The IRX-2 Regimen is a 21-day regimen of cyclophosophamide on Day 1 and
      subcutaneous IRX-2 injections for 10 days between Days 4 and 18. If no dose limiting
      toxicities (DLTs) are observed during the first 4 weeks of treatment, the enrollment will
      continue in a dose expansion phase. If there is a study treatment related DLT in 1 of 6
      patients, the same dose will be investigated at the dose expansion cohorts. If study
      treatment related DLT is observed in 2 of 6 patients, accrual will be stopped and new dose
      levels or treatment sequences will be considered.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants Who Experience Dose Limiting Toxicities (DLTs)
time frame: Up to Day 28
description: A DLT is defined as any Grade 3 or higher toxicity which occurs during the DLT evaluation period of 4 weeks (during Cycle 1 Day 1 and Cycle 1 Day 28) and considered related to study treatment. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded.
measure: Objective Response Rate
time frame: Up to 12 months
description: Objective response determined using Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 and Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria.
measure: Progression Free Survival of combination therapy
time frame: Up to 12 months
description: Progression free survival defined as the time from Day 1 of treatment to evidence of progression. Progression will be defined by RECIST Version 1.1
arm group label: IRX-2 Regimen combined with Nivolumab
arm group type: Experimental
description: IRX-2 Regimen (4 ml) combined with Nivolumab (240 mg)
intervention type: Drug
intervention name: IRX 2
description: IRX-2 Regimen: 21 day regimen of cyclophosphamide on Day 1 and subcutaneous IRX-2 injections for 10 days between Days 4 and 18. This 21 day regimen will be given every 12 weeks.
arm group label: IRX-2 Regimen combined with Nivolumab
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab 240 mg will be given via IV infusion once every 2 weeks.
arm group label: IRX-2 Regimen combined with Nivolumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rohit Jain, MD, MPH
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
country: United States
url: http://moffitt.org/clinical-trials-research/clinical-trials/
description: Moffitt Cancer Center Clinical Trials Website
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Carcinoma, Renal Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Recurrence
mesh term: Nivolumab