<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/NCT03277209</url>
  </required_header>
  <id_info>
    <org_study_id>1508016466</org_study_id>
    <nct_id>NCT03277209</nct_id>
  </id_info>
  <brief_title>To Assess the Safety of Continuous IV Administration of Plerixafor and Assess Impact on the Immune Microenvironment in Patients With Pancreatic, Ovarian and Colorectal Adenocarcinomas</brief_title>
  <official_title>To Assess the Safety of Continuous IV Administration of the CXCR4 Antagonist, Plerixafor at Potentially Active Plasma Concentrations and Assess Its Impact on the Immune Microenvironment in Patients With Advanced Pancreatic, High Grade Serous Ovarian and Colorectal Adenocarcinomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Weill Medical College of Cornell University</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A dose escalation trial to assess the safety of plerixafor in patients with advanced&#xD;
      pancreatic, high grade serous ovarian and colorectal cancer. To identify the proof of&#xD;
      mechanism, by demonstrating alterations in T-cell tumour distribution, ideally associated&#xD;
      with loss of tumour cells, measured by immunostaining, and changes in FDG uptake.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, non-randomised, open label, Phase I, dose escalation trial of&#xD;
      plerixafor in patients with histological documentation of advanced pancreatic, high grade&#xD;
      serous ovarian or colorectal adenocarcinoma. We will investigate the feasibility of&#xD;
      administering plerixafor in terms of safety, and will try to identify the proof of mechanism&#xD;
      in patients. This trial will follow the standard 3+3, Phase I trial design, leading to a&#xD;
      treatment expansion phase to confirm the RP2D.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    terminated due to slow accrual&#xD;
  </why_stopped>
  <start_date type="Actual">July 25, 2017</start_date>
  <completion_date type="Actual">December 30, 2019</completion_date>
  <primary_completion_date type="Actual">December 30, 2019</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>Causality of adverse events (AEs) and serious adverse events (SAEs) and grading according to NCI CTCAE v.4.03.</measure>
    <time_frame>From baseline through Day 56</time_frame>
    <description>Assess safety of continuous IV administration of plerixafor in doses needed to achieve and maintain circulating levels similar to those active in a murine model of PDAC (2 μg/ml)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)</measure>
    <time_frame>From baseline through Day 56</time_frame>
    <description>To explore objective anticancer clinical impact of this strategy.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in T cell distribution within tumour regions within primary or metastatic lesions (e.g. CD3+ T cell accumulation in cancer cell &quot;nests&quot;)</measure>
    <time_frame>From baseline through Day 56</time_frame>
    <description>To explore relationships between intratumoural T-cell distribution, CXCR4 and CXCL12 immunostaining and other potential biomarkers of immune activation in tissue and blood, such as circulating CD34+ cell counts and diurnal cortisol variation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in circulating tumour ctDNA levels within plasma, during and after treatment.</measure>
    <time_frame>From baseline through Day 56</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Changes in proliferation and apoptosis markers (e.g. Ki67/Mib1), changes in tumour cell populations in samples.</measure>
    <time_frame>From baseline through Day 56</time_frame>
    <description>To assess modulation of the immune tumour microenvironment following CXCR4 inhibition by plerixafor administration.</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in immune cytokine serum levels.</measure>
    <time_frame>From baseline through Day 56</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>T cell receptor (TCR) sequencing in tumour tissue.</measure>
    <time_frame>From baseline through Day 56</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>DNA and RNA sequencing in tumour tissue.</measure>
    <time_frame>From baseline through Day 56</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Evidence of systemic pharmacodynamic response to CXCR4i, such as increase in CD34+ cell numbers in blood.</measure>
    <time_frame>From baseline through Day 56</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Correlation between changes in T cell distribution and diurnal cortisol variation.</measure>
    <time_frame>From baseline through Day 56</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Pancreas Cancer</condition>
  <arm_group>
    <arm_group_label>All Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Plerixafor will be administered via IV as a continuous 7 day intravenous infusion starting at a dose of 20 ug/kg/hr and subsequent dose levels of 40, 80 and 120 ug/kg/hr</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Plerixafor</intervention_name>
    <description>Plerixafor will be administered via IV as a continuous 7 day intravenous infusion starting at a dose of 20 ug/kg/hr and subsequent dose levels of 40, 80 and 120 ug/kg/hr</description>
    <arm_group_label>All Subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 16 years or over (In the US, aged 18 years or over only).&#xD;
&#xD;
          -  Dose escalation phase only: Patients with inoperable, histologically proven locally&#xD;
             advanced or metastatic pancreatic, high grade serous ovarian or colorectal&#xD;
             adenocarcinoma, refractory to conventional chemotherapy or a patient who has declined&#xD;
             conventional chemotherapy OR;&#xD;
&#xD;
          -  Treatment expansion phase only: Patients with inoperable, histologically proven&#xD;
             locally advanced or metastatic pancreatic, refractory to conventional chemotherapy or&#xD;
             a patient who has declined conventional chemotherapy.&#xD;
&#xD;
          -  Tumour lesions considered to be accessible for core biopsy and immunostaining&#xD;
             assessment.&#xD;
&#xD;
          -  ECOG performance status 0-1.&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks.&#xD;
&#xD;
          -  All women of child-bearing potential and all sexually active male patients must agree&#xD;
             to use effective contraception methods throughout the trial and for 3 months after the&#xD;
             final dose of trial drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inadequate haematological function defined by:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &lt;1.5 x 109/L&#xD;
&#xD;
               -  Absolute lymphocyte count &lt;1.0 x 109/L (counts shall be rounded to the nearest&#xD;
                  tenth. (e.g. 0.96 will be rounded to 1.0 x 109/L))&#xD;
&#xD;
               -  Haemoglobin &lt;9.0 g/dL (90 g/L) (may be increased to this level with transfusion&#xD;
                  as long as there is no evidence of active bleeding)&#xD;
&#xD;
               -  Platelets &lt;100 x 109/L&#xD;
&#xD;
               -  Clotting; INR &gt;1.3&#xD;
&#xD;
          -  Inadequate renal function defined by calculated creatinine clearance by&#xD;
             Cockcroft-Gault of &lt;50 ml/min.&#xD;
&#xD;
          -  Inadequate hepatic function defined by:&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) &gt;2.5 x&#xD;
                  upper limit of normal (ULN) or &gt;5 x in the presence of liver metastases&#xD;
&#xD;
               -  Total bilirubin &gt;1.5 x ULN&#xD;
&#xD;
          -  Current treatment (within 28 days of entry) with chemotherapy, steroids or other&#xD;
             immunosuppressive drugs.&#xD;
&#xD;
          -  Significant acute or chronic medical or psychiatric condition, disease or laboratory&#xD;
             abnormality which in the judgment of the Investigator would place the patient at undue&#xD;
             risk or interfere with the trial.&#xD;
&#xD;
          -  Cardiac co-morbidity:&#xD;
&#xD;
               -  Past history of significant rhythm disturbance (e.g. SVT, AF or ventricular&#xD;
                  irregularities)&#xD;
&#xD;
               -  Requirement for pacemaker&#xD;
&#xD;
               -  Myocardial infarction in the previous 6 months&#xD;
&#xD;
               -  Known medical history of proven postural hypotension.&#xD;
&#xD;
          -  Active infection.&#xD;
&#xD;
          -  Patients with known allergy to plerixafor or its excipients.&#xD;
&#xD;
          -  Patients known to have hepatitis B, hepatitis C or HIV infection.&#xD;
&#xD;
          -  Participation in any other interventional clinical trial&#xD;
&#xD;
          -  Women, who are pregnant, plan to become pregnant or are lactating (during the trial or&#xD;
             for up to 3 months after the last dose)&#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>Elizabeta Popa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Duncan Jodrell, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Cambridge University Hospitals NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 6, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>February 27, 2020</last_update_submitted>
  <last_update_submitted_qc>February 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2020</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>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>Plerixafor</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/NCT03277209
org study id: 1508016466
nct id: NCT03277209
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
A dose escalation trial to assess the safety of plerixafor in patients with advanced
      pancreatic, high grade serous ovarian and colorectal cancer. To identify the proof of
      mechanism, by demonstrating alterations in T-cell tumour distribution, ideally associated
      with loss of tumour cells, measured by immunostaining, and changes in FDG uptake.
This is a prospective, non-randomised, open label, Phase I, dose escalation trial of
      plerixafor in patients with histological documentation of advanced pancreatic, high grade
      serous ovarian or colorectal adenocarcinoma. We will investigate the feasibility of
      administering plerixafor in terms of safety, and will try to identify the proof of mechanism
      in patients. This trial will follow the standard 3+3, Phase I trial design, leading to a
      treatment expansion phase to confirm the RP2D.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Causality of adverse events (AEs) and serious adverse events (SAEs) and grading according to NCI CTCAE v.4.03.
time frame: From baseline through Day 56
description: Assess safety of continuous IV administration of plerixafor in doses needed to achieve and maintain circulating levels similar to those active in a murine model of PDAC (2 μg/ml)
measure: Assessment of metabolic changes in tumour using non-invasive imaging (18FDG-PET)
time frame: From baseline through Day 56
description: To explore objective anticancer clinical impact of this strategy.
measure: Change in T cell distribution within tumour regions within primary or metastatic lesions (e.g. CD3+ T cell accumulation in cancer cell "nests")
time frame: From baseline through Day 56
description: To explore relationships between intratumoural T-cell distribution, CXCR4 and CXCL12 immunostaining and other potential biomarkers of immune activation in tissue and blood, such as circulating CD34+ cell counts and diurnal cortisol variation.
measure: Changes in circulating tumour ctDNA levels within plasma, during and after treatment.
time frame: From baseline through Day 56
measure: Changes in proliferation and apoptosis markers (e.g. Ki67/Mib1), changes in tumour cell populations in samples.
time frame: From baseline through Day 56
description: To assess modulation of the immune tumour microenvironment following CXCR4 inhibition by plerixafor administration.
measure: Changes in immune cytokine serum levels.
time frame: From baseline through Day 56
measure: T cell receptor (TCR) sequencing in tumour tissue.
time frame: From baseline through Day 56
measure: DNA and RNA sequencing in tumour tissue.
time frame: From baseline through Day 56
measure: Evidence of systemic pharmacodynamic response to CXCR4i, such as increase in CD34+ cell numbers in blood.
time frame: From baseline through Day 56
measure: Correlation between changes in T cell distribution and diurnal cortisol variation.
time frame: From baseline through Day 56
arm group label: All Subjects
arm group type: Experimental
description: Plerixafor will be administered via IV as a continuous 7 day intravenous infusion starting at a dose of 20 ug/kg/hr and subsequent dose levels of 40, 80 and 120 ug/kg/hr
intervention type: Drug
intervention name: Plerixafor
description: Plerixafor will be administered via IV as a continuous 7 day intravenous infusion starting at a dose of 20 ug/kg/hr and subsequent dose levels of 40, 80 and 120 ug/kg/hr
arm group label: All Subjects
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elizabeta Popa, MD
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
last name: Duncan Jodrell, MD
role: Study Chair
affiliation: Cambridge University Hospitals NHS Foundation Trust
facility: 
facility: 
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms
mesh term: Plerixafor