<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/NCT03781362</url>
  </required_header>
  <id_info>
    <org_study_id>CPI-CL18-001</org_study_id>
    <nct_id>NCT03781362</nct_id>
  </id_info>
  <brief_title>Study of CPI-100 in Patients With Advanced Tumors</brief_title>
  <official_title>A Phase 1, First-in-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of CPI-100 Via Intravenous Infusion in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Coordination Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Coordination Pharmaceuticals, Inc.</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 is a prospective, open-label, 2-arm, non-randomized study of CPI-100 in patients with&#xD;
      advanced tumors. CPI-100 is administered via intravenous infusion in a 3 + 3 study design to&#xD;
      identify the maximum tolerated dose (MTD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      • To determine the safety, tolerability and maximum tolerated dose (MTD) of CPI-100 as once&#xD;
      every two weeks (Q2W) and once every three weeks (Q3W) regimens in patients with advanced&#xD;
      tumors&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
        -  To evaluate the pharmacokinetics (PK) of CPI-100&#xD;
&#xD;
        -  To evaluate clinical response and resolution of symptoms after CPI-100 treatment&#xD;
&#xD;
        -  To characterize adverse events of CPI-100 monotherapy and CPI-100 in combination with&#xD;
           capecitabine in patients with advanced cancers&#xD;
&#xD;
      Up to 5 dose levels of CPI-100 Q2W, 4 dose levels of Q3W regimen of CPI-100 monotherapy (Q3W&#xD;
      Arm A) and 4 dose levels of Q3W regimen of CPI-100 in combination with capecitabine (Q3W Arm&#xD;
      B) will be tested in a dose escalation study. MTD will be defined as the dose associated with&#xD;
      a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level&#xD;
      tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from&#xD;
      the intravenous injection of CPI-100 within 28 days (Q2W) or 42 days (Q3W):&#xD;
&#xD;
        -  Grade 4 or greater treatment related adverse events&#xD;
&#xD;
        -  Any Grade 3 or greater treatment related non-hematologic, non-dermatologic toxicity&#xD;
           (including nausea, vomiting or diarrhea lasting more than 72 hours)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 21, 2018</start_date>
  <completion_date type="Actual">June 21, 2022</completion_date>
  <primary_completion_date type="Actual">June 21, 2022</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>
    <intervention_model_description>3 + 3 dose escalation study design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>28 Days</time_frame>
    <description>• To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy as assessed by CTCAE5</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit</measure>
    <time_frame>through study completion, an average of 4 months</time_frame>
    <description>• To assess clinical benefit by response rate and resolution of symptoms, which will be reported as response rate (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Effect</measure>
    <time_frame>through study completion, an average of 4 months</time_frame>
    <description>• To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax)</measure>
    <time_frame>8 Days</time_frame>
    <description>• To evaluate maximum plasma concentration (Cmax) of CPI-100 in patients tested</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve (AUC)</measure>
    <time_frame>8 Days</time_frame>
    <description>• To evaluate area under the curve (AUC) of CPI-100 in patients tested</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Advanced Tumors</condition>
  <arm_group>
    <arm_group_label>CPI-100 Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Groups:&#xD;
CPI-100 will be administered via intravenous infusion once every 2 weeks (Q2W) for up to 5 dose levels and once every 3 weeks (Q3W Arm A) for up to 4 dose levels in a 3 + 3 dose escalation study&#xD;
Dose Expansion Group: Maximum tolerated dose or the recommended Phase 2 dose (RP2D) from dose escalation group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CPI-100 Combination with Capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CPI-100 will be administered via intravenous infusion once every 3 weeks in combination with oral capecitabine for up to 4 dose levels in a dose escalation study (Q3W Arm B)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CPI-100</intervention_name>
    <description>CPI-100 will be administered via intravenous infusion on Day 1 of a 14-Day cycle</description>
    <arm_group_label>CPI-100 Combination with Capecitabine</arm_group_label>
    <arm_group_label>CPI-100 Monotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Capecitabine will be administered 1000 mg/m2 orally twice a day for 2 weeks followed by a 7-day rest period</description>
    <arm_group_label>CPI-100 Combination with Capecitabine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a histologically or cytologically confirmed diagnosis of advanced solid tumor&#xD;
&#xD;
          -  Have advanced or metastatic disease refractory to standard curative or palliative&#xD;
             therapy or contraindication to standard therapy&#xD;
&#xD;
          -  Be reasonably recovered from preceding major surgery or no major surgery within 4&#xD;
             weeks prior to the start of Day 1 treatment&#xD;
&#xD;
          -  Have a negative pregnancy test for females with child bearing age at screening and&#xD;
             should not be breast feeding&#xD;
&#xD;
          -  Be willing to abstain from sexual activity or practice physical barrier contraception&#xD;
             from study entry to 6 months after the last day of treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have peripheral neuropathy of Grade 3 or Grade 4 at screening&#xD;
&#xD;
          -  Have peripheral sensory neuropathy of Grade 2 or greater at screening&#xD;
&#xD;
          -  Have an interval from previous neurotoxic drugs less than 3 months unless reasonably&#xD;
             recovered from all grades of neurotoxicity to grade 1 or lower as judged by the&#xD;
             investigator&#xD;
&#xD;
          -  Have known hypersensitivity to chemotherapeutic agents&#xD;
&#xD;
          -  Have a history of thrombocytopenia with complications including hemorrhage or bleeding&#xD;
             &gt; Grade 2 that required medical intervention or any hemolytic condition or coagulation&#xD;
             disorders that would make participation unsafe&#xD;
&#xD;
          -  Have unresolved toxicity from previous treatment or previous investigational agents;&#xD;
             excluding alopecia&#xD;
&#xD;
          -  Is pregnant or breast-feeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>South Texas Accelerated Research Therapeutics</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Texas Accelerated Research Therapeutics</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>July 19, 2022</last_update_submitted>
  <last_update_submitted_qc>July 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intravenous infusion</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The data will not be shared due to confidentiality agreements</ipd_description>
  </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/NCT03781362
org study id: CPI-CL18-001
nct id: NCT03781362
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a prospective, open-label, 2-arm, non-randomized study of CPI-100 in patients with
      advanced tumors. CPI-100 is administered via intravenous infusion in a 3 + 3 study design to
      identify the maximum tolerated dose (MTD).
Primary Objectives:

      • To determine the safety, tolerability and maximum tolerated dose (MTD) of CPI-100 as once
      every two weeks (Q2W) and once every three weeks (Q3W) regimens in patients with advanced
      tumors

      Secondary Objectives:

        -  To evaluate the pharmacokinetics (PK) of CPI-100

        -  To evaluate clinical response and resolution of symptoms after CPI-100 treatment

        -  To characterize adverse events of CPI-100 monotherapy and CPI-100 in combination with
           capecitabine in patients with advanced cancers

      Up to 5 dose levels of CPI-100 Q2W, 4 dose levels of Q3W regimen of CPI-100 monotherapy (Q3W
      Arm A) and 4 dose levels of Q3W regimen of CPI-100 in combination with capecitabine (Q3W Arm
      B) will be tested in a dose escalation study. MTD will be defined as the dose associated with
      a dose limiting toxicity (DLT) in less than or equal to 33% of patients at the dose level
      tested. Dose limiting toxicity (DLT) is defined as one of the following events occurring from
      the intravenous injection of CPI-100 within 28 days (Q2W) or 42 days (Q3W):

        -  Grade 4 or greater treatment related adverse events

        -  Any Grade 3 or greater treatment related non-hematologic, non-dermatologic toxicity
           (including nausea, vomiting or diarrhea lasting more than 72 hours)
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: 3 + 3 dose escalation study design
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: 28 Days
description: • To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy as assessed by CTCAE5
measure: Clinical Benefit
time frame: through study completion, an average of 4 months
description: • To assess clinical benefit by response rate and resolution of symptoms, which will be reported as response rate (%)
measure: Adverse Effect
time frame: through study completion, an average of 4 months
description: • To assess adverse effect as either treatment-related or non-treatment-related as defined by CTCAE
measure: Maximum Plasma Concentration (Cmax)
time frame: 8 Days
description: • To evaluate maximum plasma concentration (Cmax) of CPI-100 in patients tested
measure: Area Under the Curve (AUC)
time frame: 8 Days
description: • To evaluate area under the curve (AUC) of CPI-100 in patients tested
arm group label: CPI-100 Monotherapy
arm group type: Experimental
description: Dose Escalation Groups:
CPI-100 will be administered via intravenous infusion once every 2 weeks (Q2W) for up to 5 dose levels and once every 3 weeks (Q3W Arm A) for up to 4 dose levels in a 3 + 3 dose escalation study
Dose Expansion Group: Maximum tolerated dose or the recommended Phase 2 dose (RP2D) from dose escalation group
arm group label: CPI-100 Combination with Capecitabine
arm group type: Experimental
description: CPI-100 will be administered via intravenous infusion once every 3 weeks in combination with oral capecitabine for up to 4 dose levels in a dose escalation study (Q3W Arm B)
intervention type: Drug
intervention name: CPI-100
description: CPI-100 will be administered via intravenous infusion on Day 1 of a 14-Day cycle
arm group label: CPI-100 Combination with Capecitabine
arm group label: CPI-100 Monotherapy
intervention type: Drug
intervention name: Capecitabine
description: Capecitabine will be administered 1000 mg/m2 orally twice a day for 2 weeks followed by a 7-day rest period
arm group label: CPI-100 Combination with Capecitabine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Capecitabine
sharing ipd: No
ipd description: The data will not be shared due to confidentiality agreements