<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/NCT04472910</url>
  </required_header>
  <id_info>
    <org_study_id>19-6059</org_study_id>
    <nct_id>NCT04472910</nct_id>
  </id_info>
  <brief_title>GATA6 Expression as a Predictor of Response to Peri-Operative Chemotherapy in Resectable Pancreatic Adenocarcinoma</brief_title>
  <acronym>NeoPancOne</acronym>
  <official_title>GATA6 Expression as a Predictor of Response to Peri-Operative Chemotherapy in Resectable Pancreatic Adenocarcinoma: A Multicentre Canadian Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pancreatic Cancer Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Health Network, Toronto</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>
      To date, there have been no Canadian led neoadjuvant or peri-operative trials, this&#xD;
      multicentre design gives the opportunity to build more experience with this strategy across&#xD;
      Canada in more institutions. The design of this prospective trial will also test our&#xD;
      important hypotheses regarding the use of biomarkers to understand the benefit of mFFX in&#xD;
      improving outcomes for patients with resectable pancreas cancer. Data from this study would&#xD;
      likely inform future studies where patients are given personalised options for the best&#xD;
      treatment strategies rather than one empiric approach.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 21, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</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>To assess disease free survival (DFS) in resectable PDAC treated with peri-operative mFFX according to baseline GATA6 expression level</measure>
    <time_frame>2-4 years</time_frame>
    <description>Disease free survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate the feasibility of EUS FNB as an effective modality for the detection of GATA6 expression at first diagnosis, including number of unsuccessful EUS-FNBs.</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine GATA6 in-situ hybridization (ISH)/immunohistochemistry (IHC) success rate</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine GATA6 expression levels in EUS-FNB specimen compared to surgical specimen</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the DFS according to R0 or R1 resection status</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the DFS according to baseline Ca19.9 levels</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the DFS according to modified Moffitt RNA classification</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the overall response rate (ORR) to neoadjuvant mFFX</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the percentage of patients who progress on neoadjuvant mFFX</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess pathological response rate to mFFX in the neoadjuvant setting</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the overall survival (OS) according to GATA6 expression level in the overall population and the GATA6 high/low populations</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the overall survival (OS) according to R0/R1 resection status in the overall population and the GATA6 high/low populations</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the overall survival (OS) according to baseline Ca19.9 levels in the overall population and the GATA6 high/low populations</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the overall survival (OS) according modified Moffitt classification in the overall population and the GATA6 high/low populations</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">84</enrollment>
  <condition>Resectable Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Neo-adjuvant mFFX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Neo-adjuvant mFFX up to 6 cycles, surgery, adjuvant chemotherapy for up tp 6 cycles, follow up</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Modified Folforinox (mFFX)</intervention_name>
    <description>Neo-adjuvant mFFX for up to 6 cycles, chemo-Adjuvant FFX q 2 weekly or other approach as per investigator to complete up to 6 months chemotherapy</description>
    <arm_group_label>Neo-adjuvant mFFX</arm_group_label>
    <other_name>Folfirinox or other approach</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a histological diagnosis of PDAC. Those with unconfirmed histology must&#xD;
             have this confirmed by EUS-FNB in the pre-screening period prior to commencement of&#xD;
             chemotherapy. Invasive PDAC in the setting of intraductal papillary mucinous neoplasm&#xD;
             (IPMN) is permitted.&#xD;
&#xD;
          -  Patients must consent to EUS-FNB for correlative analysis even if adenocarcinoma has&#xD;
             been confirmed, unless confirmation was performed using a previous biopsy or fine&#xD;
             needle biopsy with adequate tumour tissue for GATA6 analysis.&#xD;
&#xD;
          -  Resectable primary tumour on preoperative biphasic (arterial and venous phases)&#xD;
             contrast-enhanced CT for pancreatic staging as per institutional standard of care,&#xD;
             with ≤5 mm slice thickness. MRI for liver metastases (optional) as per institutional&#xD;
             standard of care. The definition of resectability (as per NCCN guidelines - see&#xD;
             Appendix B) includes:&#xD;
&#xD;
               -  no involvement of the celiac artery, common hepatic artery or superior mesenteric&#xD;
                  artery (or if present a replaced right or common hepatic artery)&#xD;
&#xD;
               -  no involvement or &lt;180 (interface between tumour and vessel wall, of the portal&#xD;
                  vein or superior mesenteric vein, and patent portal vein/splenic vein confluence_&#xD;
&#xD;
               -  For tumours of the body and tail of the pancreas, involvement of the splenic&#xD;
                  artery and vein of any degree is considered resectable disease&#xD;
&#xD;
          -  Patients must be medically fit to undergo surgical resection&#xD;
&#xD;
          -  No prior oncological treatment for index PDAC&#xD;
&#xD;
          -  ECOG Performance status 0-1&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Patients must be medically suitable for treatment with mFFX as per treating medical&#xD;
             oncologist&#xD;
&#xD;
          -  No evidence of metastases (i.e., metastatic work-up negative including a CT scan of&#xD;
             the chest, abdomen (IV and oral contrast, 3 phase) and pelvis)&#xD;
&#xD;
          -  Adequate hematologic function&#xD;
&#xD;
               -  absolute neutrophil count (ANC) ≥ 1,500 cells/mm3&#xD;
&#xD;
               -  platelets ≥ 100 000 cells/mm3&#xD;
&#xD;
               -  hemoglobin ≥ 9 g/L (after transfusion is acceptable))&#xD;
&#xD;
          -  Creatinine level &lt; 130 µmol/L or CrCl ≥ 50 ml/min&#xD;
&#xD;
          -  Patients of child-bearing potential (for female patient: study entry after a menstrual&#xD;
             period and a negative pregnancy test) must agree to use two medically acceptable&#xD;
             methods of contraception (one for the patient and one for their partner) during the&#xD;
             study and for 4 months after the last study treatment intake for women and 6 months&#xD;
             for men. These patients must have a pregnancy test repeated every month while on&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Patients must be able to provide written informed consent&#xD;
&#xD;
          -  Adequate liver function (AST &lt;2.5 times the institutional upper limit of normal at the&#xD;
             baseline visit, total bilirubin ≤ 2 times the institutional upper limit of normal at&#xD;
             the baseline visit)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients where attempted EUS-FNB x 2 has not confirmed PDAC in the setting of&#xD;
             unconfirmed histology.&#xD;
&#xD;
          -  Patients in whom histology has confirmed PDAC but who do not consent to EUS-FNB,&#xD;
             unless previous confirmation was by biopsy or fine needle biopsy with adequate tumour&#xD;
             tissue for GATA6 analysis.&#xD;
&#xD;
          -  Non-ductal pancreas tumours including endocrine tumours, acinar cell carcinoma, cyst&#xD;
             adenocarcinoma or ampullary tumours.&#xD;
&#xD;
          -  Unresectable PDAC by contrast enhanced CT or MRI. Borderline resectable PDAC (vein and&#xD;
             artery) are excluded from this study&#xD;
&#xD;
          -  Evidence of metastatic disease&#xD;
&#xD;
          -  Prior treatment for index PDAC&#xD;
&#xD;
          -  Previous autologous bone marrow transplant or stem cell rescue&#xD;
&#xD;
          -  Active hepatitis B or C infection&#xD;
&#xD;
          -  Uncontrolled inter-current illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, or&#xD;
             psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#xD;
&#xD;
          -  History of another primary cancer within the last 3 years with the exception of&#xD;
             non-melanoma skin cancer, early stage prostate cancer or curatively treated cervical&#xD;
             carcinoma in situ or other indolent malignancy (discretion of PI).&#xD;
&#xD;
          -  Pregnant or breast-feeding patients are excluded from this study as the chemotherapy&#xD;
             agents used in this study have been demonstrated or have the potential to be&#xD;
             teratogenic and there is an unknown but potential risk for adverse events in nursing&#xD;
             infants secondary to treatment of the mother&#xD;
&#xD;
          -  Patients who are being therapeutically anticoagulated with coumadin and cannot have an&#xD;
             alternative anticoagulation regimen.&#xD;
&#xD;
          -  Known hypersensitivity to any of the drugs used or their components.&#xD;
&#xD;
          -  Patients with known complete absence of dihydropyrimidine dehydrogenase (DPD)&#xD;
             activity.&#xD;
&#xD;
          -  History of QT prolongation or receiving QT prolonging medications.&#xD;
&#xD;
          -  History of Gilberts condition&#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>Jennifer Knox, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Margaret Cancer Centre, University Health Network</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anna Dodd</last_name>
    <phone>647-539-6498</phone>
    <email>anna.dodd@uhn.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Roxana Bucur</last_name>
    <phone>437-772-4354</phone>
    <email>roxana.bucur@uhn.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>BC Cancer Agency Vancouver</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suilee Quach</last_name>
      <phone>604-877-6000</phone>
      <phone_ext>674826</phone_ext>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kingston Health Sciences Centre</name>
      <address>
        <city>Kingston</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jackie Edwards</last_name>
      <phone>613-549-6666</phone>
      <phone_ext>6820</phone_ext>
    </contact>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Danielle Porplycia</last_name>
      <phone>519-685-8500</phone>
      <phone_ext>54514</phone_ext>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rose Leclerc</last_name>
      <phone>613-737-7700</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2N9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Dodd</last_name>
      <phone>647-539-6498</phone>
      <email>anna.dodd@uhn.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Hospital/Odette Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roshni Ravindranathan</last_name>
      <phone>416-480-5000</phone>
      <phone_ext>67336</phone_ext>
    </contact>
  </location>
  <location>
    <facility>
      <name>Unity Health (St. Joseph's and St. Michael's)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kate Besel</last_name>
      <phone>416-864-6060</phone>
      <phone_ext>2606</phone_ext>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gelareh Arzani</last_name>
      <phone>514-340-8222</phone>
      <phone_ext>26755</phone_ext>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>June 24, 2021</last_update_submitted>
  <last_update_submitted_qc>June 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2021</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Folfirinox</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/NCT04472910
org study id: 19-6059
nct id: NCT04472910
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
To date, there have been no Canadian led neoadjuvant or peri-operative trials, this
      multicentre design gives the opportunity to build more experience with this strategy across
      Canada in more institutions. The design of this prospective trial will also test our
      important hypotheses regarding the use of biomarkers to understand the benefit of mFFX in
      improving outcomes for patients with resectable pancreas cancer. Data from this study would
      likely inform future studies where patients are given personalised options for the best
      treatment strategies rather than one empiric approach.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To assess disease free survival (DFS) in resectable PDAC treated with peri-operative mFFX according to baseline GATA6 expression level
time frame: 2-4 years
description: Disease free survival
measure: Evaluate the feasibility of EUS FNB as an effective modality for the detection of GATA6 expression at first diagnosis, including number of unsuccessful EUS-FNBs.
time frame: 2-4 years
measure: Determine GATA6 in-situ hybridization (ISH)/immunohistochemistry (IHC) success rate
time frame: 2-4 years
measure: Determine GATA6 expression levels in EUS-FNB specimen compared to surgical specimen
time frame: 2-4 years
measure: Determine the DFS according to R0 or R1 resection status
time frame: 2-4 years
measure: Determine the DFS according to baseline Ca19.9 levels
time frame: 2-4 years
measure: Determine the DFS according to modified Moffitt RNA classification
time frame: 2-4 years
measure: To determine the overall response rate (ORR) to neoadjuvant mFFX
time frame: 2-4 years
measure: Determine the percentage of patients who progress on neoadjuvant mFFX
time frame: 2-4 years
measure: Assess pathological response rate to mFFX in the neoadjuvant setting
time frame: 2-4 years
measure: Determine the overall survival (OS) according to GATA6 expression level in the overall population and the GATA6 high/low populations
time frame: 2-4 years
measure: Determine the overall survival (OS) according to R0/R1 resection status in the overall population and the GATA6 high/low populations
time frame: 2-4 years
measure: Determine the overall survival (OS) according to baseline Ca19.9 levels in the overall population and the GATA6 high/low populations
time frame: 2-4 years
measure: Determine the overall survival (OS) according modified Moffitt classification in the overall population and the GATA6 high/low populations
time frame: 2-4 years
arm group label: Neo-adjuvant mFFX
arm group type: Experimental
description: Neo-adjuvant mFFX up to 6 cycles, surgery, adjuvant chemotherapy for up tp 6 cycles, follow up
intervention type: Drug
intervention name: Modified Folforinox (mFFX)
description: Neo-adjuvant mFFX for up to 6 cycles, chemo-Adjuvant FFX q 2 weekly or other approach as per investigator to complete up to 6 months chemotherapy
arm group label: Neo-adjuvant mFFX
other name: Folfirinox or other approach
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Knox, MD
role: Principal Investigator
affiliation: Princess Margaret Cancer Centre, University Health Network
last name: Anna Dodd
phone: 647-539-6498
email: anna.dodd@uhn.ca
last name: Roxana Bucur
phone: 437-772-4354
email: roxana.bucur@uhn.ca
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Folfirinox
sharing ipd: No