<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/NCT04469556</url>
  </required_header>
  <id_info>
    <org_study_id>PASS-01</org_study_id>
    <secondary_id>CAPCR ID: 20-5105</secondary_id>
    <nct_id>NCT04469556</nct_id>
  </id_info>
  <brief_title>Pancreatic Adenocarcinoma Signature Stratification for Treatment</brief_title>
  <acronym>PASS-01</acronym>
  <official_title>Pancreatic Adenocarcinoma Signature Stratification for Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cold Spring Harbor Laboratory</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ontario Institute for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stand Up To Cancer</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>
      This is a randomized multicentre phase II trial with a large translational component. The&#xD;
      trial will evaluate the two standard chemotherapy regimens: modified folfirinox (mFFX) and&#xD;
      gemcitabine/nab-paclitaxel (GA), in patients with untreated metastatic pancreatic ductal&#xD;
      adenocarcinoma. Integrated into this phase II trial are a number of laboratory components&#xD;
      including molecular profiling, patient derived organoid establishment, and drug testing&#xD;
      sensitivity and other biomarkers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The two chemotherapy regimens GA and mFFX remain standard treatment options without&#xD;
      biomarkers to predict response. PASS-01 will for the first time explore progression free&#xD;
      survival differences in the two standard backbone regimens used in the advanced setting.&#xD;
      Biomarker driven strategies in pancreatic ductal adenocarcinoma (PDAC) are lacking, perhaps&#xD;
      accounting for a large number of failed phase II studies. This study will evaluate two&#xD;
      standard of care chemotherapy regimens, but will also explore high content molecular&#xD;
      profiling, chemotherapy sensitivity signatures, GATA6 and other putative biomarkers as&#xD;
      predictors of response to chemotherapy. In addition, the use of patient derived organoid&#xD;
      models for personalized medicine in PDAC will continue to develop within this study.&#xD;
&#xD;
      Approximately 150 patients diagnosed with untreated metastatic pancreatic cancer will be&#xD;
      randomized to either arm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Approximately 150 patients will be randomized in a 1:1 ratio to receive one of the two standard of care regimens in patients with confirmed metastatic PDAC</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.</measure>
    <time_frame>2-4 years</time_frame>
    <description>Time from the date of randomization to progression based on the radiology assessment of response using RECIST v1.1, or death, whichever is earlier</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA</measure>
    <time_frame>2-4 years</time_frame>
    <description>percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GATA6 as a biomarker of response to mFFX or GA</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cell free circulating tumor (ct) DNA analysis (including KRAS mutational status)</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cluster Tendency analysis using artificial neural networks and radiomic methods combined</measure>
    <time_frame>2-4 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Pancreatic Cancer Metastatic</condition>
  <condition>Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Advanced Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Modified Folfirinox</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Modified FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin) administered intravenously.&#xD;
Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gemcitabine/nab-Paclitaxel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gemcitabine/nab-Paclitaxel administered intravenously.&#xD;
Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Folfirinox</intervention_name>
    <description>Chemotherapy</description>
    <arm_group_label>Modified Folfirinox</arm_group_label>
    <other_name>Folinic Acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine/nab-paclitaxel</intervention_name>
    <description>Chemotherapy</description>
    <arm_group_label>Gemcitabine/nab-Paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have a histological or radiological diagnosis of untreated metastatic&#xD;
             PDAC at screening with histology subsequently confirmed prior to randomization.&#xD;
&#xD;
          2. Eligible histologic variants include adenocarcinoma or variants to include mucinous&#xD;
             adenocarcinoma or adenosquamous carcinoma.&#xD;
&#xD;
          3. Patients with a history of prior or concurrent second primary malignancy whose natural&#xD;
             history or treatment does not have the potential to interfere with the safety or&#xD;
             primary endpoint efficacy assessment of the pancreas cancer should generally be&#xD;
             eligible for enrollment in clinical trials.&#xD;
&#xD;
          4. Age ≥18 years.&#xD;
&#xD;
          5. Patient must have a tumor lesion that is amenable to a core needle biopsy.&#xD;
&#xD;
          6. Patients must be suitable for treatment with either mFFX and GA without&#xD;
             contraindications to either regimen.&#xD;
&#xD;
          7. Eastern Cooperative Group (ECOG) performance status 0-1. (Karnofsky ≥70%).&#xD;
&#xD;
          8. Life expectancy of greater than 90 days, as judged by the investigator&#xD;
&#xD;
          9. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test and&#xD;
             must agree to use adequate contraception (hormonal or barrier method of birth control;&#xD;
             abstinence) prior to study entry and for the duration of study participation.&#xD;
&#xD;
         10. Within 14 days of the proposed randomization date, patients must have normal organ and&#xD;
             marrow function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who have received prior systemic treatment for PDAC, including treatment in&#xD;
             the neoadjuvant or adjuvant setting. Prior surgery or palliative radiation is&#xD;
             permitted.&#xD;
&#xD;
          2. Patients with histology other than pancreatic ductal adenocarcinoma. Those with&#xD;
             adenosquamous are allowed. Acinar tumors and colloid are excluded.&#xD;
&#xD;
          3. Patients with one or more contraindications to tumor biopsy according to local&#xD;
             institution's standard biopsy procedures.&#xD;
&#xD;
          4. Patients with known brain metastases are excluded from participation in this clinical&#xD;
             study.&#xD;
&#xD;
          5. Uncontrolled inter-current illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, inability to stop anticoagulation medication for a biopsy, or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirements.&#xD;
&#xD;
          6. Any other condition that would, in the Investigator's judgment, contraindicate the&#xD;
             patient's participation in the clinical study due to safety concerns or compliance&#xD;
             with clinical study procedures.&#xD;
&#xD;
          7. Patients with a known germline mutation in BRCA, PALB2 or other homologous&#xD;
             Recombination Repair Deficiency (HRD) genes.&#xD;
&#xD;
          8. Patients who are pregnant or breastfeeding.&#xD;
&#xD;
          9. Use (including 'recreational use') of any illicit drugs or other substance abuse&#xD;
             (including alcohol) that could potentially interfere with adherence to study&#xD;
             procedures or requirements. *Use of any illicit drugs or other substance abuse&#xD;
             (including alcohol) are not screened in Canada using Toxicity testing. -&#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>Elizabeth Jaffee, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jennifer J Knox, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University Health Network, Toronto</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anna J Dodd</last_name>
    <phone>416-946-2399</phone>
    <email>anna.dodd@uhn.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Johns Hopkins Sidney Kimmel Comprehensive Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniel Laheru, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kimberley Perez, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Northwell Health</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniel King, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kenneth Yu, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>BC Cancer Agency Vancouver</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 1L8</zip>
        <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>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_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>April 12, 2022</last_update_submitted>
  <last_update_submitted_qc>April 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</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>
    <mesh_term>Pancreatic Neoplasms</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>
    <mesh_term>Irinotecan</mesh_term>
    <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/NCT04469556
org study id: PASS-01
secondary id: CAPCR ID: 20-5105
nct id: NCT04469556
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a randomized multicentre phase II trial with a large translational component. The
      trial will evaluate the two standard chemotherapy regimens: modified folfirinox (mFFX) and
      gemcitabine/nab-paclitaxel (GA), in patients with untreated metastatic pancreatic ductal
      adenocarcinoma. Integrated into this phase II trial are a number of laboratory components
      including molecular profiling, patient derived organoid establishment, and drug testing
      sensitivity and other biomarkers.
The two chemotherapy regimens GA and mFFX remain standard treatment options without
      biomarkers to predict response. PASS-01 will for the first time explore progression free
      survival differences in the two standard backbone regimens used in the advanced setting.
      Biomarker driven strategies in pancreatic ductal adenocarcinoma (PDAC) are lacking, perhaps
      accounting for a large number of failed phase II studies. This study will evaluate two
      standard of care chemotherapy regimens, but will also explore high content molecular
      profiling, chemotherapy sensitivity signatures, GATA6 and other putative biomarkers as
      predictors of response to chemotherapy. In addition, the use of patient derived organoid
      models for personalized medicine in PDAC will continue to develop within this study.

      Approximately 150 patients diagnosed with untreated metastatic pancreatic cancer will be
      randomized to either arm.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Approximately 150 patients will be randomized in a 1:1 ratio to receive one of the two standard of care regimens in patients with confirmed metastatic PDAC
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.
time frame: 2-4 years
description: Time from the date of randomization to progression based on the radiology assessment of response using RECIST v1.1, or death, whichever is earlier
measure: ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA
time frame: 2-4 years
description: percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR)
measure: Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping
time frame: 2-4 years
measure: GATA6 as a biomarker of response to mFFX or GA
time frame: 2-4 years
measure: • Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)
time frame: 2-4 years
measure: • Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).
time frame: 2-4 years
measure: • Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance
time frame: 2-4 years
measure: Cell free circulating tumor (ct) DNA analysis (including KRAS mutational status)
time frame: 2-4 years
measure: Cluster Tendency analysis using artificial neural networks and radiomic methods combined
time frame: 2-4 years
arm group label: Modified Folfirinox
arm group type: Active Comparator
description: Modified FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin) administered intravenously.
Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.
arm group label: Gemcitabine/nab-Paclitaxel
arm group type: Active Comparator
description: Gemcitabine/nab-Paclitaxel administered intravenously.
Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.
intervention type: Drug
intervention name: Folfirinox
description: Chemotherapy
arm group label: Modified Folfirinox
other name: Folinic Acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin
intervention type: Drug
intervention name: Gemcitabine/nab-paclitaxel
description: Chemotherapy
arm group label: Gemcitabine/nab-Paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elizabeth Jaffee, MD
role: Study Chair
affiliation: Johns Hopkins University
last name: Jennifer J Knox, MD
role: Study Chair
affiliation: University Health Network, Toronto
last name: Anna J Dodd
phone: 416-946-2399
email: anna.dodd@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: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Pancreatic Neoplasms
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Gemcitabine
mesh term: Oxaliplatin
mesh term: Irinotecan
mesh term: Folfirinox
sharing ipd: No