<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/NCT03274778</url>
  </required_header>
  <id_info>
    <org_study_id>IOSI-IOR-001</org_study_id>
    <nct_id>NCT03274778</nct_id>
  </id_info>
  <brief_title>Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells</brief_title>
  <official_title>An Exploratory proof-of Mechanism Study to Assess the Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells and Additional Immune Subsets in Prostate Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oncology Institute of Southern Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oncology Institute of Southern Switzerland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ruxolitinib will be dispensed to patients candidate to prostatectomy immediately after&#xD;
      histological diagnosis of prostate adenocarcinoma. The treatment will be given for 28 days&#xD;
      followed by a prostatectomy thereafter.&#xD;
&#xD;
      Tumor material and blood samples will be analysed before, during and after the treatment with&#xD;
      Ruxolitinib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with suspected localized prostate cancer will undergo biopsies spotting different&#xD;
      prostate sites, as per standard clinical practice. Patients with histologically confirmed&#xD;
      prostate adenocarcinoma and candidate for prostatectomy, after signing the Informed Consent&#xD;
      Form, will receive Ruxolitinib for 4 weeks (the time normally elapsing between histological&#xD;
      diagnosis and surgery) and will thereafter undergo prostatectomy.&#xD;
&#xD;
      Remaining biological material from the diagnosis and the prostatectomy will be sent to the&#xD;
      Molecular Oncology Laboratory for molecular analysis.&#xD;
&#xD;
      In addition, blood samples will be drawn before, during Ruxolitinib treatment (Week 2), at&#xD;
      the end of treatment (Week 4), and after prostatectomy (Week 5), to assess the frequency and&#xD;
      subtype of immune subsets and the circulating levels of cytokines and secreted.&#xD;
&#xD;
      Patients will be monitored for occurrence of adverse events/surgical complications during&#xD;
      treatment and up to 4 weeks after the intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Recruitment difficulty due to eligibility criteria.&#xD;
  </why_stopped>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">March 24, 2020</completion_date>
  <primary_completion_date type="Actual">March 24, 2020</primary_completion_date>
  <phase>N/A</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>Tumor immune response</measure>
    <time_frame>9 wks</time_frame>
    <description>Tumor immune response modification induced by Ruxolitinib</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pSTAT3</measure>
    <time_frame>5 wks</time_frame>
    <description>Decrease of pSTAT3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokines</measure>
    <time_frame>6 wks</time_frame>
    <description>Reduction of cytokines associated to myeloid cells recruitment and tumor-promoting factors (e.g. IL8, IL6, TGF)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KI-67</measure>
    <time_frame>9 wks</time_frame>
    <description>Reduction by 50% of KI-67</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biomarkers</measure>
    <time_frame>5 wks</time_frame>
    <description>Increase of senescence and apoptosis markers (p16, p21, Beta-galactosidase, Caspase-3, Caspase-8)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Ruxolitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of Ruxolitinib 20mg BID for 28 consecutive days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib 20 MG</intervention_name>
    <description>tablets</description>
    <arm_group_label>Ruxolitinib</arm_group_label>
    <other_name>Jakavi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-70 years&#xD;
&#xD;
          -  Histological diagnosis of prostate adenocarcinoma&#xD;
&#xD;
          -  Stage ≥T2b for which surgery is indicated&#xD;
&#xD;
          -  No distant metastasis (M0)&#xD;
&#xD;
          -  NLR ≥3 in the blood or NLR ≥3 in the tumor biopsies or a percentage of MDSCs ≥ 30% in&#xD;
             the tumour biopsies&#xD;
&#xD;
          -  PS (ECOG scale) 0-1&#xD;
&#xD;
          -  Adequate hepatic function: ALT and ASAT ≤ 2.5 x ULN, Bilirubin ≤ 1.5 ULN (exception if&#xD;
             Gilbert's syndrome ≤ 2.5 x ULN)&#xD;
&#xD;
          -  Adequate renal function: calculated creatinine clearance ≥ 50 ml/min according to the&#xD;
             formula of Cockcroft-Gault&#xD;
&#xD;
          -  Hemoglobin ≥ 10 g/dl, leukocyte count ≥ 4.0 x 103/µl, platelet count ≥ 200 x 103/µl&#xD;
&#xD;
          -  Informed Consent as documented by the patient's signature&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No history of coagulation disorders and normal INR&#xD;
&#xD;
          -  Significant cardiovascular disorders in the last 12 months&#xD;
&#xD;
          -  Other clinically significant concomitant disease states which in the opinion of the&#xD;
             Investigator may represent contraindications to study participation&#xD;
&#xD;
          -  Known or suspected non-compliance&#xD;
&#xD;
          -  Participation in another study with investigational drug within the 30 days preceding&#xD;
             and during the present study&#xD;
&#xD;
          -  Ongoing treatment with strong CYP3A4 inhibitors or dual CYP2C9 and CYP3A4 inhibitors&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrea Alimonti, Prof.</last_name>
    <role>Study Director</role>
    <affiliation>Institute of Oncology Research (IOR)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Istituto Oncologico della Svizzera Italiana (IOSI)</name>
      <address>
        <city>Bellinzona</city>
        <zip>6500</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>March 24, 2020</last_update_submitted>
  <last_update_submitted_qc>March 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oncology Institute of Southern Switzerland</investigator_affiliation>
    <investigator_full_name>Andrea Alimonti</investigator_full_name>
    <investigator_title>Prof. dr. med.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_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/NCT03274778
org study id: IOSI-IOR-001
nct id: NCT03274778
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Ruxolitinib will be dispensed to patients candidate to prostatectomy immediately after
      histological diagnosis of prostate adenocarcinoma. The treatment will be given for 28 days
      followed by a prostatectomy thereafter.

      Tumor material and blood samples will be analysed before, during and after the treatment with
      Ruxolitinib.
Patients with suspected localized prostate cancer will undergo biopsies spotting different
      prostate sites, as per standard clinical practice. Patients with histologically confirmed
      prostate adenocarcinoma and candidate for prostatectomy, after signing the Informed Consent
      Form, will receive Ruxolitinib for 4 weeks (the time normally elapsing between histological
      diagnosis and surgery) and will thereafter undergo prostatectomy.

      Remaining biological material from the diagnosis and the prostatectomy will be sent to the
      Molecular Oncology Laboratory for molecular analysis.

      In addition, blood samples will be drawn before, during Ruxolitinib treatment (Week 2), at
      the end of treatment (Week 4), and after prostatectomy (Week 5), to assess the frequency and
      subtype of immune subsets and the circulating levels of cytokines and secreted.

      Patients will be monitored for occurrence of adverse events/surgical complications during
      treatment and up to 4 weeks after the intervention.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Tumor immune response
time frame: 9 wks
description: Tumor immune response modification induced by Ruxolitinib
measure: pSTAT3
time frame: 5 wks
description: Decrease of pSTAT3
measure: Cytokines
time frame: 6 wks
description: Reduction of cytokines associated to myeloid cells recruitment and tumor-promoting factors (e.g. IL8, IL6, TGF)
measure: KI-67
time frame: 9 wks
description: Reduction by 50% of KI-67
measure: biomarkers
time frame: 5 wks
description: Increase of senescence and apoptosis markers (p16, p21, Beta-galactosidase, Caspase-3, Caspase-8)
arm group label: Ruxolitinib
arm group type: Experimental
description: Oral administration of Ruxolitinib 20mg BID for 28 consecutive days
intervention type: Drug
intervention name: Ruxolitinib 20 MG
description: tablets
arm group label: Ruxolitinib
other name: Jakavi
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Andrea Alimonti, Prof.
role: Study Director
affiliation: Institute of Oncology Research (IOR)
facility: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: Oncology Institute of Southern Switzerland
investigator full name: Andrea Alimonti
investigator title: Prof. dr. med.
mesh term: Prostatic Neoplasms
sharing ipd: No