<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/NCT02991651</url>
  </required_header>
  <id_info>
    <org_study_id>IRX4204 NSCLC 1 01 2015</org_study_id>
    <nct_id>NCT02991651</nct_id>
  </id_info>
  <brief_title>Study of IRX4204 With Erlotinib in Previously Treated Advanced NSCLC</brief_title>
  <official_title>A Phase I Study of IRX4204 in Combination With Erlotinib in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Io Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dartmouth College</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Io Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patient selection: a) Pathological confirmation of non-small cell lung cancer without&#xD;
      activating EGFR mutations; b) Advanced stage disease (IV or IIIB with malignant effusion)&#xD;
      with at least two prior chemotherapy regimens; c) No available curative therapy; d) Pregnant&#xD;
      women are excluded; e) Informed consent.&#xD;
&#xD;
      Pretreatment evaluation: a) Medical history and physical examination; b) Hepatic and renal&#xD;
      function (bilirubin, aspartate aminotransaminase, creatinine); c) Preoperative staging&#xD;
      evaluation including CT-chest or PET/CT scan;&#xD;
&#xD;
      Treatment plan: Three dose levels of IRX4204 and erlotinib will be studied using&#xD;
      intra-patient dose escalation for dose levels 1 and 2. These study agents will be&#xD;
      administered orally until progression of disease, unacceptable toxicities, activation of a&#xD;
      phase II study of the combination, or exhaustion of the IRX4204 drug supply.&#xD;
&#xD;
      Evaluation on study: Adverse events will be graded on a scale of 0 to 5, using the Common&#xD;
      Terminology Criteria for Adverse Events (CTCAE) v. 4.0. Efficacy will be assessed using the&#xD;
      RECIST v1.1 criteria based on CT-chest or PET/CT scan after 8 weeks of study treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Numerous studies in pre-clinical models and in human clinical trials have clearly established&#xD;
      the potential for the use of rexinoids in the treatment and prevention of cancer. IRX4204, a&#xD;
      second generation rexinoid, is a highly potent and specific activator of RXRs. Because&#xD;
      IRX4204 is significantly more potent and more selective for the RXRs relative to the RARs&#xD;
      than a first generation approved RXR agonist drug, bexarotene, it potentially will be&#xD;
      associated with fewer adverse events and greater activity in clinical use. Preclinical&#xD;
      studies of the combination of IRX4204 plus erlotinib, and previous clinical studies of the&#xD;
      combination of the bexarotene plus erlotinib indicated at least additive beneficial effects&#xD;
      for treatment of NSCLC. This study seeks to investigate the safety and activity of IRX4204 in&#xD;
      combination with erlotinib in patients with previously treated advanced NSCLC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Limited IRX4204 Study Drug Supply&#xD;
  </why_stopped>
  <start_date>May 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of co-administration of IRX4204 + erlotinib to determine recommended phase 2 dose based on number of participants experiencing treatment-related adverse events as assessed as grade 4 by CTCAE v4.0</measure>
    <time_frame>30 days</time_frame>
    <description>To determine the recommended phase II dose (RP2D) for the combination of IRX4204 and erlotinib.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>toxicity profile of the combination of IRX4204 and erlotinib based on number of participants experiencing treatment-related grades 1-4 adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>one month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease control rate (defined as rate of stable disease + partial response + complete response)</measure>
    <time_frame>six months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>progression free survival (PFS)</measure>
    <time_frame>six months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival (OS)</measure>
    <time_frame>six months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>response rate by RECIST 1.1</measure>
    <time_frame>six months</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Lung Cancer, Nonsmall Cell</condition>
  <arm_group>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IRX4204 5 mg/day PO + erlotinib 100 mg/day PO</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IRX4204 5 mg/day PO + erlotinib 150 mg/day PO</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IRX4204 10 mg/day PO + erlotinib 150 mg/day PO</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IRX4204</intervention_name>
    <description>RXR agonist</description>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>erlotinib</intervention_name>
    <description>inhibitor of phosphorylation of the tyrosine kinase associated with the epidermal growth factor receptor</description>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed stage IV non-small cell&#xD;
             lung cancer, or recurrent non-small cell lung cancer which is not amenable to curative&#xD;
             intent therapy.&#xD;
&#xD;
          -  Documented disease progression on at least two prior lines of chemotherapy for&#xD;
             advanced NSCLC. Progression within 6 months of adjuvant chemotherapy or definitive&#xD;
             chemoradiation will count as one line of therapy.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  ECOG performance status ≤2.&#xD;
&#xD;
          -  Ability to take pills by mouth.&#xD;
&#xD;
          -  Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
          -  Leukocytes ≥3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count ≥1,500/mcL&#xD;
&#xD;
          -  Platelets ≥100,000/mcL&#xD;
&#xD;
          -  Hemoglobin ≥8.5 g/dL&#xD;
&#xD;
          -  Total bilirubin ≤1.5 x institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  AST(SGOT)/ALT(SGPT) ≤2.5 × ULN or ≤5 x ULN if metastases to the liver&#xD;
&#xD;
          -  Creatinine clearance ≥40 mL/min&#xD;
&#xD;
          -  Patients with asymptomatic brain metastases are allowed, as long as they are stable&#xD;
             and do not require treatment with anticonvulsants or escalating doses of steroids.&#xD;
             Maximum daily dose of steroids should be prednisone 20 mg or equivalent. Radiation&#xD;
             therapy for brain metastases must be completed at least 14 days prior to treatment on&#xD;
             protocol.&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use highly effective&#xD;
             contraception (if using hormonal birth control must add a second barrier method;&#xD;
             abstinence) prior to study entry, for the duration of study participation as well as&#xD;
             for at least 1 month after the last dose of IRX4204. Men treated or enrolled on this&#xD;
             protocol must also agree to use highly effective contraception prior to the study, for&#xD;
             the duration of study participation and 3 months after completion of IRX4204&#xD;
             administration.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering&#xD;
             the study.&#xD;
&#xD;
          -  Activating EGFR mutations detected in the tumor.&#xD;
&#xD;
          -  Prior treatment with an EGFR tyrosine kinase inhibitor.&#xD;
&#xD;
          -  Prior treatment with IRX4204 or another retinoid or rexinoid administered for the&#xD;
             purpose of cancer treatment. Prior topical retinoid use is allowed.&#xD;
&#xD;
          -  History of allergic reactions attributed to IRX4204 or erlotinib or to compounds of&#xD;
             similar chemical or biologic composition.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Pregnant and nursing women.&#xD;
&#xD;
          -  Patients with a history of another active malignancy within the past two years, with&#xD;
             the exception of non-melanoma cutaneous malignancy, cervical carcinoma in situ, or&#xD;
             ductal carcinoma in situ which has been successfully treated with curative intent&#xD;
             therapy.&#xD;
&#xD;
          -  Any gastrointestinal disorder expected to limit absorption of IRX4204 or erlotinib.&#xD;
&#xD;
          -  Patients with a history of active thyroid disease. However, patients with a history of&#xD;
             hypothyroidism maintained in euthyroid state by supplementation with thyroid hormone,&#xD;
             or a thyroid hormone containing preparation may be enrolled.&#xD;
&#xD;
          -  Patients taking coumarin-derived anticoagulants.&#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>Martin E Sanders, MD</last_name>
    <role>Study Director</role>
    <affiliation>Io Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Geisel School of Medicine at Dartmouth</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>March 29, 2022</last_update_submitted>
  <last_update_submitted_qc>March 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>RXR agonist IRX4204 erlotinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erlotinib Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02991651
org study id: IRX4204 NSCLC 1 01 2015
nct id: NCT02991651
lead sponsor: 
collaborator: 
has dmc: No
Patient selection: a) Pathological confirmation of non-small cell lung cancer without
      activating EGFR mutations; b) Advanced stage disease (IV or IIIB with malignant effusion)
      with at least two prior chemotherapy regimens; c) No available curative therapy; d) Pregnant
      women are excluded; e) Informed consent.

      Pretreatment evaluation: a) Medical history and physical examination; b) Hepatic and renal
      function (bilirubin, aspartate aminotransaminase, creatinine); c) Preoperative staging
      evaluation including CT-chest or PET/CT scan;

      Treatment plan: Three dose levels of IRX4204 and erlotinib will be studied using
      intra-patient dose escalation for dose levels 1 and 2. These study agents will be
      administered orally until progression of disease, unacceptable toxicities, activation of a
      phase II study of the combination, or exhaustion of the IRX4204 drug supply.

      Evaluation on study: Adverse events will be graded on a scale of 0 to 5, using the Common
      Terminology Criteria for Adverse Events (CTCAE) v. 4.0. Efficacy will be assessed using the
      RECIST v1.1 criteria based on CT-chest or PET/CT scan after 8 weeks of study treatment.
Numerous studies in pre-clinical models and in human clinical trials have clearly established
      the potential for the use of rexinoids in the treatment and prevention of cancer. IRX4204, a
      second generation rexinoid, is a highly potent and specific activator of RXRs. Because
      IRX4204 is significantly more potent and more selective for the RXRs relative to the RARs
      than a first generation approved RXR agonist drug, bexarotene, it potentially will be
      associated with fewer adverse events and greater activity in clinical use. Preclinical
      studies of the combination of IRX4204 plus erlotinib, and previous clinical studies of the
      combination of the bexarotene plus erlotinib indicated at least additive beneficial effects
      for treatment of NSCLC. This study seeks to investigate the safety and activity of IRX4204 in
      combination with erlotinib in patients with previously treated advanced NSCLC.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of co-administration of IRX4204 + erlotinib to determine recommended phase 2 dose based on number of participants experiencing treatment-related adverse events as assessed as grade 4 by CTCAE v4.0
time frame: 30 days
description: To determine the recommended phase II dose (RP2D) for the combination of IRX4204 and erlotinib.
measure: toxicity profile of the combination of IRX4204 and erlotinib based on number of participants experiencing treatment-related grades 1-4 adverse events as assessed by CTCAE v4.0
time frame: one month
measure: disease control rate (defined as rate of stable disease + partial response + complete response)
time frame: six months
measure: progression free survival (PFS)
time frame: six months
measure: overall survival (OS)
time frame: six months
measure: response rate by RECIST 1.1
time frame: six months
arm group label: Dose Level 1
arm group type: Experimental
description: IRX4204 5 mg/day PO + erlotinib 100 mg/day PO
arm group label: Dose Level 2
arm group type: Experimental
description: IRX4204 5 mg/day PO + erlotinib 150 mg/day PO
arm group label: Dose Level 3
arm group type: Experimental
description: IRX4204 10 mg/day PO + erlotinib 150 mg/day PO
intervention type: Drug
intervention name: IRX4204
description: RXR agonist
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
intervention type: Drug
intervention name: erlotinib
description: inhibitor of phosphorylation of the tyrosine kinase associated with the epidermal growth factor receptor
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martin E Sanders, MD
role: Study Director
affiliation: Io Therapeutics, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Erlotinib Hydrochloride
sharing ipd: No