<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/NCT04452461</url>
  </required_header>
  <id_info>
    <org_study_id>5076</org_study_id>
    <nct_id>NCT04452461</nct_id>
  </id_info>
  <brief_title>Pancreatic Adenocarcinoma Neoadjuvant Combination Chemotherapy and Stereotactic Body Radiation Therapy Before Surgery</brief_title>
  <acronym>PANCREAS</acronym>
  <official_title>mFOLFIRINOX or Gemcitabine / Nab-paclitaxel and Stereotactic Body Radiation Therapy Followed by Pancreatectomy for Patients With Borderline Resectable Pancreatic Adenocarcinoma. A Pilot Feasibility Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hamilton Health Sciences Corporation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hamilton Health Sciences Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-arm, single-center feasibility trial of patients with borderline resectable&#xD;
      pancreatic adenocarcinoma receiving chemotherapy with mFOLFIRINOX or gemcitabine /&#xD;
      nab-paclitaxel followed by pancreatectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Borderline resectable pancreatic adenocarcinoma infiltrates into adjacent vascular structures&#xD;
      to an extent such that complete macroscopic resection is technically feasible, but an R0&#xD;
      resection poses a challenge when surgery is the primary therapy. Therefore, a different&#xD;
      management strategy may be beneficial.&#xD;
&#xD;
      The primary outcome of the PANCREAS trial is defined as the proportion of eligible patients&#xD;
      enrolled in the study over an 18-month period and the proportion of patients who complete the&#xD;
      protocol (neoadjuvant therapy and pancreatectomy). Certain modifications of the neoadjuvant&#xD;
      therapy protocol are expected and allowed, and the primary feasibility outcome will be one of&#xD;
      the following: stop, main study non-feasible; continue with protocol modifications; or&#xD;
      continue without modification. A safety analysis will be performed after first 15 patients&#xD;
      are enrolled and complete neoadjuvant therapy and surgery. Patients enrolled in this trial&#xD;
      will undergo interventions in the following order: neoadjuvant chemotherapy, re-staging CT&#xD;
      scan, pancreatectomy and adjuvant chemotherapy. Postoperative mortality will be recorded up&#xD;
      to 90 days after surgery. Patients will be followed every four months with a CT scan of the&#xD;
      chest/abdomen for two years after resection or until evidence of disease recurrence. Patients&#xD;
      who do not undergo surgical resection will be followed for two years after accrual (duration&#xD;
      of study period) or until evidence of disease progression or death.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2021</start_date>
  <completion_date type="Anticipated">May 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2024</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>Proportion of patients eligible enrolled</measure>
    <time_frame>18 months</time_frame>
    <description>Over an 18-month period The proportion of patients who complete the protocol (neoadjuvant therapy and pancreatectomy). As described, there are certain modifications of the neoadjuvant therapy protocol that are expected and allowed. The primary feasibility outcome will be one of the following:&#xD;
Stop, main study non-feasible: 1) estimated proportion of eligible patients enrolled &lt;40% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) &lt;40%.&#xD;
Continue with protocol modifications: 1) estimated proportion of eligible patients enrolled between 40-59% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) 40-59%.&#xD;
Continue without modification: 1) estimated proportion of eligible patients enrolled equal to or greater than 60% or estimated proportion of enrolled patients who complete the protocol (neoadjuv</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>24 months</time_frame>
    <description>Defined as percentage of patients alive at two years from enrolment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>24 months from the initiation of chemotherapy (the length of the study)</time_frame>
    <description>Defined as the duration of time from enrolment to time to radiological evidence of disease progression or recurrence or death, whichever comes first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Complications from surgery</measure>
    <time_frame>From date of surgery (POD=0) up to 90 postoperative days (POD=90)</time_frame>
    <description>Occurrence of any postoperative complication (major or minor) from surgery following each patient's hospital stay and up to 90 days from the initial operation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathological response to chemo-radiation treatment</measure>
    <time_frame>From the date of the first chemotherapy to the date of surgery (around 4 months)</time_frame>
    <description>Pathological response to treatment will be classified as per protocol.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Pancreatic Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Single Arm Intervention</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Chemotherapy: 6 cycles (three months) of IV combination chemotherapy with mFOLFIRINOX on day 1 followed by one week of rest (14-day cycle). Alternatively, patients will receive three months of gemcitabine / nab-paclitaxel.&#xD;
Re-staging CT scan with Carbohydrate Antigen (CA) 19-9 serum test.&#xD;
Staging laparoscopy to rule out occult metastatic disease is optional based on surgeon's preference.&#xD;
5. Pancreatectomy 4 weeks following the last day of Chemotherapy as per standard of care.&#xD;
6. Adjuvant chemotherapy: as per standard of care. 7. Clinical assessment and CT scan with CA 19-9 serum test at 4-month intervals until identification of cancer recurrence.&#xD;
8. Follow up of patients after 2 years every six months for up to 5 years following the initiation of treatment will be performed off-protocol as per standard of care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mFOLFIRINOX</intervention_name>
    <description>mFOLFIRINOX, including: Oxaliplatin 85 mg/m2 IV over 2 hours, Leucovorin 400mg/m2 IV over 2 hours, Irinotecan at 150 mg/m2 IV over 90 min, 5-Fluoruracil continuous infusion of 2400 mg/m2 IV over 46h.</description>
    <arm_group_label>Single Arm Intervention</arm_group_label>
    <other_name>5-FU</other_name>
    <other_name>leucovorin</other_name>
    <other_name>oxaliplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine / Nab-paclitaxel</intervention_name>
    <description>Both drugs are administered once weekly for three weeks (days 1, 8, 15) followed by a week of rest (28-day cycle) for 3 cycles prior to imaging. Gemcitabine: 1000 mg/m2 intravenous infusion over 30 to 40 minutes. Nab-paclitaxel: 125 mg/m2 intravenous infusion over 30 to 40 minutes.</description>
    <arm_group_label>Single Arm Intervention</arm_group_label>
    <other_name>gemcitabine / abraxane</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Men and women 18 years of age or older who present with biopsy proven borderline&#xD;
             resectable pancreatic adenocarcinoma who are medically fit for surgery as per&#xD;
             assessment by treating surgeon.&#xD;
&#xD;
             2. Age ≤ 79 years 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1&#xD;
             4. Normal bone marrow and organ function&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) = or &gt; 1500, platelets &gt; 100K&#xD;
&#xD;
               2. Total bilirubin &lt;1.5x upper limit of normal (ULN)&#xD;
&#xD;
               3. Alanine transaminase (ALT), Aspartate aminotransferase (AST) &lt; 3 x ULN&#xD;
&#xD;
               4. Creatinine &lt;150umol/L&#xD;
&#xD;
               5. Normal prothrombin time and international normalized ratio (INR) 5. Able to&#xD;
                  provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Proven metastatic disease (e.g. on imaging modality such as CT scan of the chest,&#xD;
             abdomen and pelvis or MRI)&#xD;
&#xD;
          2. Locally advanced pancreatic cancer (see definition section 3.3)&#xD;
&#xD;
          3. Prior treatment with radiation therapy to the pancreas or associated field.&#xD;
&#xD;
          4. Contraindications to receive chemotherapy&#xD;
&#xD;
          5. History of cardiac disease including congestive heart failure (New York Heart&#xD;
             Association class 2), active coronary artery disease or uncontrolled hypertension&#xD;
&#xD;
          6. Concurrent ongoing systemic infections&#xD;
&#xD;
          7. Illegal substance abuse, or social conditions that may interfere with patient's&#xD;
             participation in the trial&#xD;
&#xD;
          8. Pre-existing neuropathy&#xD;
&#xD;
          9. Pregnant patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Leyo Ruo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Leyo Ruo, MD</last_name>
    <phone>905-521-2100</phone>
    <phone_ext>76626</phone_ext>
    <email>ruol@mcmaster.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pablo E Serrano, MD</last_name>
    <phone>905-521-2100</phone>
    <phone_ext>43872</phone_ext>
    <email>serrano@mcmaster.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Juravinski Hospital</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V1C3</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Leyo Ruo, MD</last_name>
      <phone>905-521-2100</phone>
      <phone_ext>76626</phone_ext>
      <email>ruol@mcmaster.ca</email>
    </contact>
    <contact_backup>
      <last_name>Pablo E Serrano, MD</last_name>
      <phone>905-521-2100</phone>
      <phone_ext>43872</phone_ext>
      <email>serrano@mcmaster.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Pablo E Serrano, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Brandon Meyers, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christian van der Pol, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tariq Aziz, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sameer Parpia, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kimmen Quan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>August 5, 2022</last_update_submitted>
  <last_update_submitted_qc>August 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hamilton Health Sciences Corporation</investigator_affiliation>
    <investigator_full_name>Pablo Serrano</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
  </intervention_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/NCT04452461
org study id: 5076
nct id: NCT04452461
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a single-arm, single-center feasibility trial of patients with borderline resectable
      pancreatic adenocarcinoma receiving chemotherapy with mFOLFIRINOX or gemcitabine /
      nab-paclitaxel followed by pancreatectomy.
Borderline resectable pancreatic adenocarcinoma infiltrates into adjacent vascular structures
      to an extent such that complete macroscopic resection is technically feasible, but an R0
      resection poses a challenge when surgery is the primary therapy. Therefore, a different
      management strategy may be beneficial.

      The primary outcome of the PANCREAS trial is defined as the proportion of eligible patients
      enrolled in the study over an 18-month period and the proportion of patients who complete the
      protocol (neoadjuvant therapy and pancreatectomy). Certain modifications of the neoadjuvant
      therapy protocol are expected and allowed, and the primary feasibility outcome will be one of
      the following: stop, main study non-feasible; continue with protocol modifications; or
      continue without modification. A safety analysis will be performed after first 15 patients
      are enrolled and complete neoadjuvant therapy and surgery. Patients enrolled in this trial
      will undergo interventions in the following order: neoadjuvant chemotherapy, re-staging CT
      scan, pancreatectomy and adjuvant chemotherapy. Postoperative mortality will be recorded up
      to 90 days after surgery. Patients will be followed every four months with a CT scan of the
      chest/abdomen for two years after resection or until evidence of disease recurrence. Patients
      who do not undergo surgical resection will be followed for two years after accrual (duration
      of study period) or until evidence of disease progression or death.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients eligible enrolled
time frame: 18 months
description: Over an 18-month period The proportion of patients who complete the protocol (neoadjuvant therapy and pancreatectomy). As described, there are certain modifications of the neoadjuvant therapy protocol that are expected and allowed. The primary feasibility outcome will be one of the following:
Stop, main study non-feasible: 1) estimated proportion of eligible patients enrolled <40% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) <40%.
Continue with protocol modifications: 1) estimated proportion of eligible patients enrolled between 40-59% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) 40-59%.
Continue without modification: 1) estimated proportion of eligible patients enrolled equal to or greater than 60% or estimated proportion of enrolled patients who complete the protocol (neoadjuv
measure: Survival
time frame: 24 months
description: Defined as percentage of patients alive at two years from enrolment.
measure: Time to Progression
time frame: 24 months from the initiation of chemotherapy (the length of the study)
description: Defined as the duration of time from enrolment to time to radiological evidence of disease progression or recurrence or death, whichever comes first.
measure: Overall Complications from surgery
time frame: From date of surgery (POD=0) up to 90 postoperative days (POD=90)
description: Occurrence of any postoperative complication (major or minor) from surgery following each patient's hospital stay and up to 90 days from the initial operation.
measure: Pathological response to chemo-radiation treatment
time frame: From the date of the first chemotherapy to the date of surgery (around 4 months)
description: Pathological response to treatment will be classified as per protocol.
arm group label: Single Arm Intervention
arm group type: Other
description: Chemotherapy: 6 cycles (three months) of IV combination chemotherapy with mFOLFIRINOX on day 1 followed by one week of rest (14-day cycle). Alternatively, patients will receive three months of gemcitabine / nab-paclitaxel.
Re-staging CT scan with Carbohydrate Antigen (CA) 19-9 serum test.
Staging laparoscopy to rule out occult metastatic disease is optional based on surgeon's preference.
5. Pancreatectomy 4 weeks following the last day of Chemotherapy as per standard of care.
6. Adjuvant chemotherapy: as per standard of care. 7. Clinical assessment and CT scan with CA 19-9 serum test at 4-month intervals until identification of cancer recurrence.
8. Follow up of patients after 2 years every six months for up to 5 years following the initiation of treatment will be performed off-protocol as per standard of care.
intervention type: Drug
intervention name: mFOLFIRINOX
description: mFOLFIRINOX, including: Oxaliplatin 85 mg/m2 IV over 2 hours, Leucovorin 400mg/m2 IV over 2 hours, Irinotecan at 150 mg/m2 IV over 90 min, 5-Fluoruracil continuous infusion of 2400 mg/m2 IV over 46h.
arm group label: Single Arm Intervention
other name: 5-FU
other name: leucovorin
other name: oxaliplatin
intervention type: Drug
intervention name: Gemcitabine / Nab-paclitaxel
description: Both drugs are administered once weekly for three weeks (days 1, 8, 15) followed by a week of rest (28-day cycle) for 3 cycles prior to imaging. Gemcitabine: 1000 mg/m2 intravenous infusion over 30 to 40 minutes. Nab-paclitaxel: 125 mg/m2 intravenous infusion over 30 to 40 minutes.
arm group label: Single Arm Intervention
other name: gemcitabine / abraxane
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
last name: Leyo Ruo, MD
role: Principal Investigator
affiliation: McMaster University
last name: Leyo Ruo, MD
phone: 905-521-2100
phone ext: 76626
email: ruol@mcmaster.ca
last name: Pablo E Serrano, MD
phone: 905-521-2100
phone ext: 43872
email: serrano@mcmaster.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Hamilton Health Sciences Corporation
investigator full name: Pablo Serrano
investigator title: Associate Professor
mesh term: Adenocarcinoma
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Oxaliplatin
sharing ipd: No