<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/NCT03822936</url>
  </required_header>
  <id_info>
    <org_study_id>CNAO 35/2017 C</org_study_id>
    <nct_id>NCT03822936</nct_id>
  </id_info>
  <brief_title>Carbon Ions Radiation Therapy for Resectable or Borderline Resectable Pancreas Adenocarcinoma</brief_title>
  <acronym>PIOPPO</acronym>
  <official_title>Phase II Clinical Study on Resectable or Borderline Resectable Pancreas Adenocarcinoma Preoperative Treatment With Chemotherapy and Carbon Ions Radiation Therapy (Hadrontherapy)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CNAO National Center of Oncological Hadrontherapy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Foundation IRCCS San Matteo Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>CNAO National Center of Oncological Hadrontherapy</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>
      Relapses free survival will be evaluated as efficacy of carbon ions radiation therapy&#xD;
      released before surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Enrolled subjects will undergo to 3 cycles of Folfirinox before re-evaluation of the lesion.&#xD;
      Then, 4D planning and imaging with respiratory gating end rescanning technique will be&#xD;
      adopted to calculate the optimal treatment plan to carbon ions radiation therapy: 38.4&#xD;
      Gy[RBE] is the prescribed dose to CTV. 4.8 Gy[RBE]/fraction will be delivered 4 times a week&#xD;
      in two weeks. 4/6 weeks after hadrontherapy, after a CT scan with contrast, patient will&#xD;
      undergo to a surgery. After 4/6 weeks, Gemcitabine will be administered for 6 cycles.&#xD;
&#xD;
      Secondary endpoints of the trial are overall survival, resectability rate (operable vs&#xD;
      borderline operable), acute toxicity within 3 months, 3-6 months, over 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 8, 2018</start_date>
  <completion_date type="Anticipated">February 8, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 8, 2023</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>The trial enrolls subjects that will receive in order: chemotherapy, carbon ion therapy, followed by surgical resection after 4/6 weeks then adjuvant chemotherapy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>The local progression free survival will be assessed at 1-year</time_frame>
    <description>The local progression free survival is measured</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>The overall survival of enrolled patients will be assessed at 2-years</time_frame>
    <description>the overall survival of enrolled patients is considered</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>resectability rate R0 stratified (operable vs not operable)</measure>
    <time_frame>time of surgery (4-6 weeks after radiotherapy)</time_frame>
    <description>how many surgeries completed according to the procedures and with histopathological margins free from the disease/enrolled patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of acute, medium term and late toxicity according to CTCAE v 4.0 grading toxicity</measure>
    <time_frame>The incidence of acute and medium term toxicity will be assessed up to 90 and 180 post-operative days respectively. The incidence of late toxicity will be assessed through study completion, an average of 1 year.</time_frame>
    <description>Incidence of acute, medium term and late toxicity according to CTCAE v 4.0 grading toxicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>intra and perioperatory complications</measure>
    <time_frame>The incidence of intra- and perioperatory complications will be assessed up to 30 post-operative days</time_frame>
    <description>intra and perioperatory complications</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Cancer of Pancreas</condition>
  <condition>Pancreas Adenocarcinoma</condition>
  <condition>Resectable Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Preoperatory chemoradiation therapy with carbon ions</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Chemoradiation followed by surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Preoperative chemotherapy</intervention_name>
    <description>Preoperative chemotherapy, carbon ion therapy, surgery</description>
    <arm_group_label>Preoperatory chemoradiation therapy with carbon ions</arm_group_label>
    <other_name>Folinic acid, Irinotecan, fluorouracil, oxaliplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Preoperative radiotherapy</intervention_name>
    <description>Preoperative chemotherapy, carbon ion therapy, surgery</description>
    <arm_group_label>Preoperatory chemoradiation therapy with carbon ions</arm_group_label>
    <other_name>Carbon ion therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologic/cytologic diagnosis of exocrine pancreas tumour&#xD;
&#xD;
          -  resectable or borderline resectable exocrine pancreatic tumour (according to&#xD;
             operability criteria)&#xD;
&#xD;
          -  no metastasis from US, CT, PET, MRI or laparotomy&#xD;
&#xD;
          -  Karnofsky index &gt;= 70&#xD;
&#xD;
          -  stomach and duodenum not infiltrated by tumour&#xD;
&#xD;
          -  given informed consent to study procedures&#xD;
&#xD;
          -  Hb &gt; 9 g/dL, N&gt; 1500, PLT&gt; 100000&#xD;
&#xD;
          -  creatininemia &lt; 1.5 mg/dL; bilirubinemia &lt; 1.5 times upper normal values; albumin &gt; 3&#xD;
             g/dL&#xD;
&#xD;
          -  DPD normal activity&#xD;
&#xD;
          -  contraception required and breast feeding not permitted&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  non resectable, locally advanced tumours&#xD;
&#xD;
          -  insular cells tumour&#xD;
&#xD;
          -  comorbidities excluding abdominal surgery and/or chemo- radiation therapy&#xD;
&#xD;
          -  known metastasis&#xD;
&#xD;
          -  DPD low activity&#xD;
&#xD;
          -  inability to attend study procedures and follow ups&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  previous diagnosis of other tumour with more disadvantageous prognosis then the study&#xD;
             object&#xD;
&#xD;
          -  metallic biliary stent&#xD;
&#xD;
          -  metallic prothesis or any other condition to prevent from target volume individuation&#xD;
             and dose calculation&#xD;
&#xD;
          -  clinical condition preventing from radiation therapy (i.e. infections in the&#xD;
             irradiation area)&#xD;
&#xD;
          -  medical and/or psychical condition preventing from radiation therapy&#xD;
&#xD;
          -  past radiation therapy on abdomen.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesca Valvo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CNAO National Center of Oncological Hadrontherapy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Francesca Valvo, MD</last_name>
    <phone>0039(0)382078501</phone>
    <phone_ext>612</phone_ext>
    <email>francesca.valvo@cnao.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Direzione medica</last_name>
    <phone>0039(0)382078501</phone>
    <email>direzionemedica@cnao.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CNAO</name>
      <address>
        <city>Pavia</city>
        <zip>27100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cristina Bono, MSc</last_name>
      <phone>+39(0)382078613</phone>
      <email>cristina.bono@cnao.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>August 31, 2021</last_update_submitted>
  <last_update_submitted_qc>August 31, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>CNAO National Center of Oncological Hadrontherapy</investigator_affiliation>
    <investigator_full_name>Francesca Valvo</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>carbon ion radiation therapy</keyword>
  <keyword>exocrine pancreas</keyword>
  <keyword>pancreas tumour</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>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</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/NCT03822936
org study id: CNAO 35/2017 C
nct id: NCT03822936
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Relapses free survival will be evaluated as efficacy of carbon ions radiation therapy
      released before surgery.
Enrolled subjects will undergo to 3 cycles of Folfirinox before re-evaluation of the lesion.
      Then, 4D planning and imaging with respiratory gating end rescanning technique will be
      adopted to calculate the optimal treatment plan to carbon ions radiation therapy: 38.4
      Gy[RBE] is the prescribed dose to CTV. 4.8 Gy[RBE]/fraction will be delivered 4 times a week
      in two weeks. 4/6 weeks after hadrontherapy, after a CT scan with contrast, patient will
      undergo to a surgery. After 4/6 weeks, Gemcitabine will be administered for 6 cycles.

      Secondary endpoints of the trial are overall survival, resectability rate (operable vs
      borderline operable), acute toxicity within 3 months, 3-6 months, over 6 months.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The trial enrolls subjects that will receive in order: chemotherapy, carbon ion therapy, followed by surgical resection after 4/6 weeks then adjuvant chemotherapy.
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: The local progression free survival will be assessed at 1-year
description: The local progression free survival is measured
measure: overall survival
time frame: The overall survival of enrolled patients will be assessed at 2-years
description: the overall survival of enrolled patients is considered
measure: resectability rate R0 stratified (operable vs not operable)
time frame: time of surgery (4-6 weeks after radiotherapy)
description: how many surgeries completed according to the procedures and with histopathological margins free from the disease/enrolled patients
measure: Incidence of acute, medium term and late toxicity according to CTCAE v 4.0 grading toxicity
time frame: The incidence of acute and medium term toxicity will be assessed up to 90 and 180 post-operative days respectively. The incidence of late toxicity will be assessed through study completion, an average of 1 year.
description: Incidence of acute, medium term and late toxicity according to CTCAE v 4.0 grading toxicity
measure: intra and perioperatory complications
time frame: The incidence of intra- and perioperatory complications will be assessed up to 30 post-operative days
description: intra and perioperatory complications
arm group label: Preoperatory chemoradiation therapy with carbon ions
arm group type: Experimental
description: Chemoradiation followed by surgery
intervention type: Drug
intervention name: Preoperative chemotherapy
description: Preoperative chemotherapy, carbon ion therapy, surgery
arm group label: Preoperatory chemoradiation therapy with carbon ions
other name: Folinic acid, Irinotecan, fluorouracil, oxaliplatin
intervention type: Radiation
intervention name: Preoperative radiotherapy
description: Preoperative chemotherapy, carbon ion therapy, surgery
arm group label: Preoperatory chemoradiation therapy with carbon ions
other name: Carbon ion therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Francesca Valvo, MD
role: Principal Investigator
affiliation: CNAO National Center of Oncological Hadrontherapy
last name: Francesca Valvo, MD
phone: 0039(0)382078501
phone ext: 612
email: francesca.valvo@cnao.it
last name: Direzione medica
phone: 0039(0)382078501
email: direzionemedica@cnao.it
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: CNAO National Center of Oncological Hadrontherapy
investigator full name: Francesca Valvo
investigator title: Principal investigator
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Irinotecan