<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/NCT04477343</url>
  </required_header>
  <id_info>
    <org_study_id>UGIP20027</org_study_id>
    <nct_id>NCT04477343</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety and Tolerability of SX-682 in Combination With Nivolumab as a Maintenance Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma</brief_title>
  <official_title>An Open-label Phase 1 Study to Evaluate the Safety and Tolerability of SX-682 in Combination With Nivolumab as a Maintenance Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Syntrix Biosystems, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The main purpose of this research study is to determine the maximum tolerable dose (MTD) of&#xD;
      SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal&#xD;
      adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment&#xD;
      without evidence of disease progression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study the investigator would like to better understand the maximum tolerable dose&#xD;
      (MTD) of SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal&#xD;
      adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment&#xD;
      without evidence of disease progression. In addition, the investigator would like to measure&#xD;
      the SX-682 pharmacokinetic data in humans. The investigator would also like to assess the&#xD;
      immunophenotypic and stromal changes to the tumor microenvironment after treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 23, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <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>Maximum tolerable dose [Safety and Tolerability]</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>Maximum tolerable dose is defined by less than or equal to 30% dose limiting toxicity (DLT) event rate within a given dose combination,</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months</time_frame>
    <description>Measure of time from study enrollment until progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From date of enrollment until date of death from any cause up to 24 months</time_frame>
    <description>Measure of time from study enrollment until death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Experimental: SX-682 and Nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SX-682 Dose: 25, 50, 100, 200, 400mg BID taken as an oral pill&#xD;
Nivolumab Dose: 240mg, every 2 weeks via intravenous infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SX-682</intervention_name>
    <description>Allosteric inhibitor to human CXCR1 and CXCR2 receptor</description>
    <arm_group_label>Experimental: SX-682 and Nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab Injectable Product</intervention_name>
    <description>humanized monoclonal antibody to program cell death receptor 1 (PD1)</description>
    <arm_group_label>Experimental: SX-682 and Nivolumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Written Informed Consent and HIPAA Authorization&#xD;
&#xD;
          1. Subjects must have the nature of the study explained to them&#xD;
&#xD;
          2. Subjects must be willing and able to comply with scheduled visits, treatment schedule,&#xD;
             laboratory tests, pharmacokinetic collections, study biopsies and other requirements&#xD;
             of the study.&#xD;
&#xD;
          3. Subjects (or an acceptable proxy) must provide a signed and dated IRB/IEC approved&#xD;
             written informed consent form (ICF) in accordance with regulatory and institutional&#xD;
             guidelines for both the study and exploratory biomarker analysis obtained via paired&#xD;
             biopsies.&#xD;
&#xD;
          4. Subjects (or an acceptable proxy) must provide a signed and dated Health Insurance&#xD;
             Portability and Accountability Act (HIPAA) authorization.&#xD;
&#xD;
          5. The ICF and HIPAA authorization must be obtained before conduction and procedures that&#xD;
             do not form a part of the subject's normal care.&#xD;
&#xD;
          6. After signing the ICF and HIPAA Authorization, subjects will be evaluated for study&#xD;
             eligibility during the Screening Period (no more than 28 days before study drug&#xD;
             administration) according to the following further inclusion/exclusion criteria:&#xD;
&#xD;
        Study Population/Inclusion Criteria&#xD;
&#xD;
          1. Male or female subjects, aged at least 18 years&#xD;
&#xD;
          2. Have histologically or cytologically confirmed metastatic pancreatic ductal&#xD;
             adenocarcinoma&#xD;
&#xD;
          3. Completion of at least 16 weeks of first line chemotherapy without evidence of disease&#xD;
             progression&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.&#xD;
&#xD;
          5. Must have measurable disease with at least 1 unidimensional measurable lesion per&#xD;
             iRECIST&#xD;
&#xD;
          6. Screening laboratory values within 14 days prior to first dose of study drug:&#xD;
&#xD;
             WBC ≥ 3000/µL Neutrophils ≥ 1500/µL Platelets ≥ 100,000&gt;µL Hemoglobin ≥ 9.0 g/dL in&#xD;
             the absence of blood transfusion Creatinine ≤ 1.5 mg/dL AST/ALT ≤ 2.5 x ULN for&#xD;
             subjects with no liver metastases&#xD;
&#xD;
               -  5 x ULN for subjects with liver metastases Bilirubin ≤ 1.5 mg/dL sa≤ 3.0 mg/dL&#xD;
                  for subjects with Gilbert's disease INR or PT ≤ 1.5 x ULN unless receiving&#xD;
                  anticoagulation therapy aPTT or PTT ≤ 1.5 x ULN unless receiving anticoagulation&#xD;
                  therapy&#xD;
&#xD;
          7. Life expectancy of ≥ 12 weeks as judged by the treating physician.&#xD;
&#xD;
          8. Patient must consent for baseline and on treatment biopsies&#xD;
&#xD;
          9. Patients must have baseline pulse oximetry ≥ 90% on room air&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Target Disease Exceptions:&#xD;
&#xD;
        Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are&#xD;
        eligible if these have been treated and there is no magnetic resonance imaging (MRI- except&#xD;
        where contraindicated, in which case a CT scan is acceptable) evidence of progression for&#xD;
        at least 8 weeks after treatment is complete and within 28 days prior to first dose of&#xD;
        study drug administration. An MRI is not required to rule out brain metastases or&#xD;
        leptomeningeal metastases. There must also be no requirement for high doses of systemic&#xD;
        corticosteroids that could result in immunosuppression (&gt;10 mg/day prednisone equivalents)&#xD;
        for at least 2 weeks prior to study dry administration.&#xD;
&#xD;
        Medical History and Concurrent Disease&#xD;
&#xD;
        Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may&#xD;
        increase the risk associated with study participation or study drug administration, impair&#xD;
        the ability of the subject to receive protocol therapy, or interfere with the&#xD;
        interpretation of study results. Specifically:&#xD;
&#xD;
          1. Subjects with active, non-infectious pneumonitis.&#xD;
&#xD;
          2. Subjects with interstitial lung disease or a history of pneumonitis that required oral&#xD;
             or intravenous glucocorticoids to assist with management.&#xD;
&#xD;
          3. Subjects with clinically significant heart disease that affects normal activities.&#xD;
&#xD;
          4. Clinically significant cardiovascular/ cerebrovascular disease defined as cerebral&#xD;
             vascular accident, stroke, carotid artery disease transient ischemic attach (&lt; 6&#xD;
             months prior to enrollment), myocardial infarction (&lt;6 months prior to enrollment),&#xD;
             unstable angina, congestive heart failure (New York Heart Association Classification&#xD;
             Class &gt;II) or serious cardiac arrhythmia.&#xD;
&#xD;
          5. Prior malignancy active within the previous 3 years except for locally curable cancers&#xD;
             that have been apparently cured, such as basal or squamous cell skin cancer,&#xD;
             superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast.&#xD;
&#xD;
          6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,&#xD;
             type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only&#xD;
             requiring hormone replacement, psoriasis not requiring systemic treatment, or&#xD;
             conditions not expected to recur in the absence of an external trigger are permitted&#xD;
             to enroll.&#xD;
&#xD;
          7. Subjects with a condition (including organ or bone marrow transplant) requiring&#xD;
             systemic treatment with either corticosteroids (&gt; 10 mg daily prednisone equivalents)&#xD;
             or other immunosuppressive medications. Inhaled or topical steroids, and adrenal&#xD;
             replacement doses &gt; 10 mg daily prednisone equivalents are permitted in the absence of&#xD;
             active autoimmune disease.&#xD;
&#xD;
          8. Use of other investigational drugs (drugs not marketed for any indication) or&#xD;
             medications at immunosuppressive doses within 28 days before study drug&#xD;
             administration.&#xD;
&#xD;
          9. Patients who received immunotherapy or investigational drug within 4 weeks prior to&#xD;
             enrollment.&#xD;
&#xD;
         10. Patients who underwent major surgery within 4 weeks of enrollment (not including&#xD;
             diagnostic laparoscopy)&#xD;
&#xD;
         11. History of myelodysplastic syndromes or myeloproliferative neoplasms.&#xD;
&#xD;
         12. History of or medication induced prolonged QT interval.&#xD;
&#xD;
         13. Any botanical preparation (e.g., herbal supplements or traditional Chinese medicines)&#xD;
             intended to treat the disease under study or provide supportive care. Use of marijuana&#xD;
             and its derivatives for treatment of symptoms related to cancer treatment, even if&#xD;
             obtained by medical prescription or if its use (even without a medical prescription)&#xD;
             has been legalized locally.&#xD;
&#xD;
        Physical and Laboratory Test Findings&#xD;
&#xD;
          1. A history of Hepatitis B or C, either acute or chronic, as indicated by HBV surface&#xD;
             antigen positivity, HBV core antibody positivity, or positive HCV antibody with reflex&#xD;
             to positive HCV RNA.&#xD;
&#xD;
          2. Known history of testing positive for human immunodeficiency virus (HIV) or known&#xD;
             acquired immunodeficiency syndrome (AIDS).&#xD;
&#xD;
          3. Active tuberculosis (history of exposure or history of positive tuberculosis test plus&#xD;
             presence of clinical symptoms, physical or radiographic findings).&#xD;
&#xD;
          4. EKG demonstrating a QTc interval &gt;470 msec or patients with congenital long QT&#xD;
             syndrome.&#xD;
&#xD;
        Allergies and Adverse Drug Reaction&#xD;
&#xD;
          1. History of allergy to study drug components (examples: hydroxpropylmethylcellulose&#xD;
             phthalate (hypromellose phthalate or HPMCP), microcrystalline cellulose, sodium&#xD;
             croscarmellose, sodium lauryl sulfate, and silicon dioxide).&#xD;
&#xD;
          2. History of severe hypersensitivity reaction to any monoclonal antibody (Grade ≥ 3&#xD;
             NCI-CTCAE v5).&#xD;
&#xD;
          3. History of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma.&#xD;
&#xD;
        Sex and Reproductive Status/Special Populations&#xD;
&#xD;
          1. Women of childbearing potential (WOCBP) must use method(s) of contraception with a&#xD;
             failure rate of less than 1% while on study and for 5 months after the last dose of&#xD;
             SX-682 or nivolumab. A WOCBP is defined as any female who has experienced menarche and&#xD;
             who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy)&#xD;
             or is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea&#xD;
             in a woman over age 45 in the absence of other biological or physiological causes.&#xD;
&#xD;
          2. Women under the age of 62 with a history of being postmenopausal must have a&#xD;
             documented serum follicle stimulating hormone, (FSH) level &gt; 40 mIU/mL.&#xD;
&#xD;
          3. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L&#xD;
             or equivalent units of HCG) within 24 hours prior to the start of study drug.&#xD;
&#xD;
          4. Women must not be breastfeeding.&#xD;
&#xD;
          5. Men who are sexually active with WOCBP must use any contraceptive method with a&#xD;
             failure rate of less than 1% per year while on study and for a period at least 7&#xD;
             months after the last dose of study drug.&#xD;
&#xD;
          6. Women who are not of childbearing potential and azoospermic men do not require&#xD;
             contraception.&#xD;
&#xD;
          7. Individuals who are incarcerated, compulsory detained or otherwise considered a&#xD;
             vulnerable population&#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>Richard Dunne, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester Wilmot Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chris LeFeber</last_name>
    <phone>585-275-0407</phone>
    <email>Chris_LeFeber@URMC.Rochester.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chris LeFeber</last_name>
      <phone>585-275-0407</phone>
      <email>Chris_LeFeber@URMC.Rochester.edu</email>
    </contact>
    <investigator>
      <last_name>Richard Dunne</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>August 8, 2023</last_update_submitted>
  <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Richard Dunne</investigator_full_name>
    <investigator_title>Professor - Department of Medicine , Hematology/Oncology</investigator_title>
  </responsible_party>
  <keyword>Pancreatic Ductal Adenocarcinoma</keyword>
  <keyword>Pancreatic Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Pancreatic Neoplasms</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/NCT04477343
org study id: UGIP20027
nct id: NCT04477343
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this research study is to determine the maximum tolerable dose (MTD) of
      SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal
      adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment
      without evidence of disease progression.
In this study the investigator would like to better understand the maximum tolerable dose
      (MTD) of SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal
      adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment
      without evidence of disease progression. In addition, the investigator would like to measure
      the SX-682 pharmacokinetic data in humans. The investigator would also like to assess the
      immunophenotypic and stromal changes to the tumor microenvironment after treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerable dose [Safety and Tolerability]
time frame: through study completion, an average of 6 months
description: Maximum tolerable dose is defined by less than or equal to 30% dose limiting toxicity (DLT) event rate within a given dose combination,
measure: Progression Free Survival
time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
description: Measure of time from study enrollment until progression.
measure: Overall Survival
time frame: From date of enrollment until date of death from any cause up to 24 months
description: Measure of time from study enrollment until death from any cause.
arm group label: Experimental: SX-682 and Nivolumab
arm group type: Experimental
description: SX-682 Dose: 25, 50, 100, 200, 400mg BID taken as an oral pill
Nivolumab Dose: 240mg, every 2 weeks via intravenous infusion
intervention type: Drug
intervention name: SX-682
description: Allosteric inhibitor to human CXCR1 and CXCR2 receptor
arm group label: Experimental: SX-682 and Nivolumab
intervention type: Drug
intervention name: Nivolumab Injectable Product
description: humanized monoclonal antibody to program cell death receptor 1 (PD1)
arm group label: Experimental: SX-682 and Nivolumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Dunne, MD
role: Principal Investigator
affiliation: University of Rochester Wilmot Cancer Center
last name: Chris LeFeber
phone: 585-275-0407
email: Chris_LeFeber@URMC.Rochester.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Richard Dunne
investigator title: Professor - Department of Medicine , Hematology/Oncology
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms
mesh term: Nivolumab