<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/NCT02984501</url>
  </required_header>
  <id_info>
    <org_study_id>20/13 PAR ComEt CBM</org_study_id>
    <nct_id>NCT02984501</nct_id>
  </id_info>
  <brief_title>Study of Induction Chemotherapy Followed by Radiochemotherapy in Locally Advanced Pancreatic Cancer</brief_title>
  <official_title>Phase II Study of Induction Chemotherapy Followed by Chemoradiotherapy in Patients With Borderline Resectable and Unresectable Locally Advanced Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Campus Bio-Medico University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Campus Bio-Medico University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is no a clear consensus regarding the optimal treatment of locally advanced pancreatic&#xD;
      disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease&#xD;
      with chemotherapy, as well as for the treatment of local disease with radiotherapy. The&#xD;
      investigators evaluated the safety and efficacy of induction chemotherapy with oxaliplatin&#xD;
      and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy&#xD;
      in patients with borderline resectable and unresectable locally advanced pancreatic cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Continued optimization in multimodality therapy and an accurate patient selection remain&#xD;
      crucial points for the appropriate treatment of patients with pancreatic cancer.&#xD;
&#xD;
      In all patients an accurate pre-treatment staging was performed, including: physical&#xD;
      examination, complete blood tests and tumor markers, endoscopic ultrasonography (EUS) with&#xD;
      fine needle aspiration biopsy, multilayer CT scan, PET-CT (positron emission computed&#xD;
      tomography) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and laparoscopy with peritoneal&#xD;
      washing. Jaundiced patients before or during treatment underwent endoscopic biliary stenting.&#xD;
&#xD;
      Patients with the evidence of metastatic disease were excluded, and thus only a small number&#xD;
      of patients was consequently enrolled with this neoadjuvant approach.&#xD;
&#xD;
      The induction phase of the treatment plan was designed to administer gemcitabine 1000 mg/mq&#xD;
      and oxaliplatin 100 mg/mq every 14 days for four doses.&#xD;
&#xD;
      In the combined phase of the treatment all patients underwent simulation by using a Siemens&#xD;
      16-CT simulator (Siemens Medical System). Radiotherapy target volumes were established by CT&#xD;
      scan and PET-CT scan.&#xD;
&#xD;
      Four weeks after the completion of radiochemotherapy, restaging, consisting of clinical&#xD;
      examination, laboratory test, tumor markers, CT scan and PET-CT scan, was performed. Tumor&#xD;
      response was defined in accordance with the World Health Organization (WHO) definition&#xD;
      through CT scan and PET-CT scan. Surgery was considered in patients whose tumors were&#xD;
      technically resectable.&#xD;
&#xD;
      After resection, patients were evaluated every three months by means of a standard&#xD;
      surveillance protocol that included history and physical examination, cross-sectional imaging&#xD;
      and measurement of serum markers, and the intervals were extended to six months after two&#xD;
      years&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">August 2016</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>four months</time_frame>
    <description>During treatment, patients are evaluated through a directed history, weekly physical examination and blood exams. The occurrence and nature of any adverse events are recorded in accordance with the National Cancer Institute Common Toxicity Criteria (version 4.0) scale. When multiple treatment-related adverse events of the same type occurred in the same patient, only the most severe ones are reported. Subsequently, the dose of chemotherapy is adjusted according to the number of occurrences of grade 2 or greater events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>metastases-free survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Local-regional Tumor Control</measure>
    <time_frame>3 years</time_frame>
    <description>Patients are not considered to have local-regional control unless they achieve at least a partial response of their primary tumor or stable disease by imaging. Patients who do not achieve objective response are considered to have local-regional failure. Local-regional control rates are analyzed using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with induction chemotherapy with gemcitabine and oxaliplatin; for patients without disease progression as detected through restaging exams, chemotherapy was followed by radiochemotherapy which consisted of conformal radiation therapy and concurrent gemcitabine at the dose of 600 mg/mq weekly.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation</intervention_name>
    <description>Radiotherapy target volumes are established by CT scan and PET-CT scan. Radiotherapy is delivered with a total dose of 54-59 Gy with fractionation of 1.8 Gy daily for 5 days a week. The Planning Target Volume (PTV) is defined by CTV with a safety margin of 1cm in all directions to include organ motion and set-up errors. Organs at risk for radiation-induced side effects are contoured on the dose planning CT and dose volume histograms (DVH) are calculated. All treatments are delivered with a 15-MV linear accelerator (Varian Medical System) with a multifield isocentric technique using a multileaf collimator. A quality-control protocol are applied for all patients with periodical digital portal images to evaluate the precision of the set-up.</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>Neoadjuvant therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chemotherapy</intervention_name>
    <description>The induction phase of the treatment plan is designed to administer gemcitabine 1000 mg/mq and oxaliplatin 100 mg/mq every 14 days for four doses. Chemotherapy concurrent to conformal radiation therapy is gemcitabine at the dose of 600 mg/mq weekly.</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>Induction therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  proven cytological or histological diagnosis of pancreatic ductal adenocarcinoma;&#xD;
&#xD;
          -  borderline resectable or unresectable pancreatic tumours;&#xD;
&#xD;
          -  age between 18 and 75 years;&#xD;
&#xD;
          -  no previous radiochemotherapy to abdomen;&#xD;
&#xD;
          -  0-I ECOG (Eastern Cooperative Oncology Group) performance status;&#xD;
&#xD;
          -  adequate cardiac, liver and kidney function and a good bone marrow reserve.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  resectable and metastatic disease;&#xD;
&#xD;
          -  previous or concomitant malignant disease;&#xD;
&#xD;
          -  one or more of the following clinical conditions: infection, pregnancy or&#xD;
             breast-feeding, liver failure, kidney failure, Pa O2 &lt; 65 mmHg, Pa CO2 &gt; 40 mmHg,&#xD;
             mental disability.&#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>Lucio Trodella, MD</last_name>
    <role>Study Director</role>
    <affiliation>Campus Bio-Medico University</affiliation>
  </overall_official>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>December 2, 2016</last_update_submitted>
  <last_update_submitted_qc>December 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 7, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Campus Bio-Medico University</investigator_affiliation>
    <investigator_full_name>Michele Fiore</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>radiochemotherapy</keyword>
  <keyword>neoadjuvant therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic 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/NCT02984501
org study id: 20/13 PAR ComEt CBM
nct id: NCT02984501
lead sponsor: 
has dmc: No
There is no a clear consensus regarding the optimal treatment of locally advanced pancreatic
      disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease
      with chemotherapy, as well as for the treatment of local disease with radiotherapy. The
      investigators evaluated the safety and efficacy of induction chemotherapy with oxaliplatin
      and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy
      in patients with borderline resectable and unresectable locally advanced pancreatic cancer
Continued optimization in multimodality therapy and an accurate patient selection remain
      crucial points for the appropriate treatment of patients with pancreatic cancer.

      In all patients an accurate pre-treatment staging was performed, including: physical
      examination, complete blood tests and tumor markers, endoscopic ultrasonography (EUS) with
      fine needle aspiration biopsy, multilayer CT scan, PET-CT (positron emission computed
      tomography) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and laparoscopy with peritoneal
      washing. Jaundiced patients before or during treatment underwent endoscopic biliary stenting.

      Patients with the evidence of metastatic disease were excluded, and thus only a small number
      of patients was consequently enrolled with this neoadjuvant approach.

      The induction phase of the treatment plan was designed to administer gemcitabine 1000 mg/mq
      and oxaliplatin 100 mg/mq every 14 days for four doses.

      In the combined phase of the treatment all patients underwent simulation by using a Siemens
      16-CT simulator (Siemens Medical System). Radiotherapy target volumes were established by CT
      scan and PET-CT scan.

      Four weeks after the completion of radiochemotherapy, restaging, consisting of clinical
      examination, laboratory test, tumor markers, CT scan and PET-CT scan, was performed. Tumor
      response was defined in accordance with the World Health Organization (WHO) definition
      through CT scan and PET-CT scan. Surgery was considered in patients whose tumors were
      technically resectable.

      After resection, patients were evaluated every three months by means of a standard
      surveillance protocol that included history and physical examination, cross-sectional imaging
      and measurement of serum markers, and the intervals were extended to six months after two
      years
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events
time frame: four months
description: During treatment, patients are evaluated through a directed history, weekly physical examination and blood exams. The occurrence and nature of any adverse events are recorded in accordance with the National Cancer Institute Common Toxicity Criteria (version 4.0) scale. When multiple treatment-related adverse events of the same type occurred in the same patient, only the most severe ones are reported. Subsequently, the dose of chemotherapy is adjusted according to the number of occurrences of grade 2 or greater events.
measure: Overall Survival
time frame: 3 years
measure: Progression-free survival
time frame: 3 years
measure: metastases-free survival
time frame: 3 years
measure: Incidence of Local-regional Tumor Control
time frame: 3 years
description: Patients are not considered to have local-regional control unless they achieve at least a partial response of their primary tumor or stable disease by imaging. Patients who do not achieve objective response are considered to have local-regional failure. Local-regional control rates are analyzed using the Kaplan-Meier method.
arm group label: Single Arm
arm group type: Experimental
description: Patients treated with induction chemotherapy with gemcitabine and oxaliplatin; for patients without disease progression as detected through restaging exams, chemotherapy was followed by radiochemotherapy which consisted of conformal radiation therapy and concurrent gemcitabine at the dose of 600 mg/mq weekly.
intervention type: Radiation
intervention name: Radiation
description: Radiotherapy target volumes are established by CT scan and PET-CT scan. Radiotherapy is delivered with a total dose of 54-59 Gy with fractionation of 1.8 Gy daily for 5 days a week. The Planning Target Volume (PTV) is defined by CTV with a safety margin of 1cm in all directions to include organ motion and set-up errors. Organs at risk for radiation-induced side effects are contoured on the dose planning CT and dose volume histograms (DVH) are calculated. All treatments are delivered with a 15-MV linear accelerator (Varian Medical System) with a multifield isocentric technique using a multileaf collimator. A quality-control protocol are applied for all patients with periodical digital portal images to evaluate the precision of the set-up.
arm group label: Single Arm
other name: Neoadjuvant therapy
intervention type: Drug
intervention name: Chemotherapy
description: The induction phase of the treatment plan is designed to administer gemcitabine 1000 mg/mq and oxaliplatin 100 mg/mq every 14 days for four doses. Chemotherapy concurrent to conformal radiation therapy is gemcitabine at the dose of 600 mg/mq weekly.
arm group label: Single Arm
other name: Induction therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Lucio Trodella, MD
role: Study Director
affiliation: Campus Bio-Medico University
responsible party type: Principal Investigator
investigator affiliation: Campus Bio-Medico University
investigator full name: Michele Fiore
investigator title: MD
mesh term: Pancreatic Neoplasms
sharing ipd: No