<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/NCT04481204</url>
  </required_header>
  <id_info>
    <org_study_id>2020-0075</org_study_id>
    <secondary_id>NCI-2020-04886</secondary_id>
    <secondary_id>2020-0075</secondary_id>
    <nct_id>NCT04481204</nct_id>
  </id_info>
  <brief_title>New and Emerging Therapies for the Treatment of Resectable, Borderline Resectable, or Locally Advanced Pancreatic Cancer, PIONEER-Panc Study</brief_title>
  <official_title>PIONEER-Panc: Phase II Investigations of New and Emerging Therapies for Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase II study using the Bayesian platform design. There are three clinical stage&#xD;
      groups of localized pancreatic cancer: resectable, borderline resectable, and locally&#xD;
      advanced disease. Each stage group will have a defined standard of care chemotherapy regimen&#xD;
      for a control arm, serving as a basis of comparison. Each group may have one or more&#xD;
      experimental arms. Experimental arms may be added to the platform over time, and the effects&#xD;
      of the experimental treatments will be tested against the controls for each group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate major pathological response rate. (Resectable and borderline resectable groups&#xD;
      [treatment naive or previously treated]) II. To estimate 6-month disease control rate.&#xD;
      (Locally advanced groups [treatment naive or previously treated])&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To measure progression free survival and overall survival. (Resectable and borderline&#xD;
      resectable groups [treatment naive or previously treated]) II. To measure progression free&#xD;
      survival and overall survival. (Locally advanced groups [treatment naive or previously&#xD;
      treated])&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To benchmark tissue acquisition protocols for deoxyribonucleic acid (DNA) and ribonucleic&#xD;
      acid (RNA) analysis in pancreatic ductal adenocarcinoma (PDAC).&#xD;
&#xD;
      II. To demonstrate concordance of cell free DNA detected mutations to those detected in the&#xD;
      tumor-derived DNA in PDAC.&#xD;
&#xD;
      III. To demonstrate response through exosome and circulating tumor DNA. IV. To demonstrate&#xD;
      response through the quantification of the immune activation by analyzing T and B cells,&#xD;
      peripheral blood mononuclear cells, and tissue biopsies.&#xD;
&#xD;
      V. To derive organoids from human PDAC and measure drug response in vitro. VI. To analyze the&#xD;
      tumor microenvironment through immunohistochemistry (IHC) and hypoxia staining.&#xD;
&#xD;
      VII. To associate prognosis of patients with baseline and follow-up quantitative computed&#xD;
      tomography (CT) image based analysis.&#xD;
&#xD;
      VIII. To associate clinical and pathological outcomes of patients with changes in radiomic&#xD;
      measurements.&#xD;
&#xD;
      IX. To correlate quality of life for patients on standard and experimental therapies with&#xD;
      laboratory, radiological, pathological, and clinical characteristics.&#xD;
&#xD;
      OUTLINE:Patients are assigned to different groups, and each group has a control arm. Within&#xD;
      each group, the patient will be randomized to the appropriate control or an experimental arm.&#xD;
      The control arms for the groups are:&#xD;
&#xD;
      Control arm for Group I (Treatment-naive resectable PDAC): Patients receive fluorouracil,&#xD;
      irinotecan, leucovorin, and oxaliplatin (mFOLFIRINOX) for 3 months before and after surgery&#xD;
      in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      Control arm for Group II (Previously-treated resectable PDAC): Patients receive gemcitabine,&#xD;
      gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months&#xD;
      in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      Control arm for Group III (Treatment-naive borderline resectable PDAC): Patients receive&#xD;
      FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity.&#xD;
      Patients may then undergo radiation therapy at the discretion of medical doctors.&#xD;
&#xD;
      Control arm for Group IV (Previously-treated borderline resectable PDAC): Patients receive&#xD;
      gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6&#xD;
      months in the absence of disease progression or unacceptable toxicity. Patients may then&#xD;
      undergo radiation therapy at the discretion of medical doctors.&#xD;
&#xD;
      Control arm for Group V (Treatment-naive locally advanced PDAC): Patients receive FOLFIRINOX&#xD;
      for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may&#xD;
      then undergo radiation therapy at the discretion of medical doctors.&#xD;
&#xD;
      Control arm for Group VI (Previously-treated locally advanced PDAC): Patients receive&#xD;
      gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6&#xD;
      months in the absence of disease progression or unacceptable toxicity. Patients may then&#xD;
      undergo radiation therapy at the discretion of medical doctors.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 16 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 18, 2023</start_date>
  <completion_date type="Anticipated">April 6, 2025</completion_date>
  <primary_completion_date type="Anticipated">April 6, 2025</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Major pathological response rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Major pathological response is any patient who has grade I or II treatment response. Grade I - 0% residual tumor cells in the specimen (pathologic complete response, grade II - 1 to &lt; 5% residual tumor cells in the specimen.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>6 months</time_frame>
    <description>Measured as the proportion of patients without progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>From the date of treatment initiation to the date of disease progression, recurrence after surgery or death from any cause whichever occurs first, assessed up to 5 years</time_frame>
    <description>Will be estimated using the Kaplan-Meier method. Comparisons of these time-to-event endpoints by important covariate subgroups will be made using the log-rank tests. Cox proportional hazards regression models will be explored to evaluate the associations between the time-to-event endpoints and covariates of interest.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From treatment start till death or last follow-up if the patient is alive, assessed up to 5 years</time_frame>
    <description>Will be estimated using the Kaplan-Meier method. Comparisons of these time-to-event endpoints by important covariate subgroups will be made using the log-rank tests. Cox proportional hazards regression models will be explored to evaluate the associations between the time-to-event endpoints and covariates of interest.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">105</enrollment>
  <condition>Borderline Resectable Pancreatic Adenocarcinoma</condition>
  <condition>Locally Advanced Pancreatic Ductal Adenocarcinoma</condition>
  <condition>Resectable Pancreatic Ductal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Control arm GroupI(mFOLFIRINOX)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive mFOLFIRINOX for 3 months before and after surgery in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm GroupIII(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm GroupV(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <other_name>Abiplatin</other_name>
    <other_name>Blastolem</other_name>
    <other_name>Briplatin</other_name>
    <other_name>CDDP</other_name>
    <other_name>Cis-diammine-dichloroplatinum</other_name>
    <other_name>Cis-diamminedichloridoplatinum</other_name>
    <other_name>Cis-diamminedichloro Platinum (II)</other_name>
    <other_name>Cis-diamminedichloroplatinum</other_name>
    <other_name>Cis-dichloroammine Platinum (II)</other_name>
    <other_name>Cis-platinous Diamine Dichloride</other_name>
    <other_name>Cis-platinum</other_name>
    <other_name>Cis-platinum II</other_name>
    <other_name>Cis-platinum II Diamine Dichloride</other_name>
    <other_name>Cismaplat</other_name>
    <other_name>Cisplatina</other_name>
    <other_name>Cisplatinum</other_name>
    <other_name>Cisplatyl</other_name>
    <other_name>Citoplatino</other_name>
    <other_name>Citosin</other_name>
    <other_name>Cysplatyna</other_name>
    <other_name>DDP</other_name>
    <other_name>Lederplatin</other_name>
    <other_name>Metaplatin</other_name>
    <other_name>Neoplatin</other_name>
    <other_name>Peyrone''s Chloride</other_name>
    <other_name>Peyrone''s Salt</other_name>
    <other_name>Placis</other_name>
    <other_name>Plastistil</other_name>
    <other_name>Platamine</other_name>
    <other_name>Platiblastin</other_name>
    <other_name>Platiblastin-S</other_name>
    <other_name>Platinex</other_name>
    <other_name>Platinol</other_name>
    <other_name>Platinol- AQ</other_name>
    <other_name>Platinol-AQ</other_name>
    <other_name>Platinol-AQ VHA Plus</other_name>
    <other_name>Platinoxan</other_name>
    <other_name>Platinum</other_name>
    <other_name>Platinum Diamminodichloride</other_name>
    <other_name>Platiran</other_name>
    <other_name>Platistin</other_name>
    <other_name>Platosin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Control arm GroupI(mFOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupIII(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupV(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <other_name>5 Fluorouracil</other_name>
    <other_name>5 Fluorouracilum</other_name>
    <other_name>5 FU</other_name>
    <other_name>5-Fluoro-2,4(1H, 3H)-pyrimidinedione</other_name>
    <other_name>5-Fluorouracil</other_name>
    <other_name>5-Fluracil</other_name>
    <other_name>5-Fu</other_name>
    <other_name>5FU</other_name>
    <other_name>AccuSite</other_name>
    <other_name>Carac</other_name>
    <other_name>Fluoro Uracil</other_name>
    <other_name>Fluouracil</other_name>
    <other_name>Flurablastin</other_name>
    <other_name>Fluracedyl</other_name>
    <other_name>Fluracil</other_name>
    <other_name>Fluril</other_name>
    <other_name>Fluroblastin</other_name>
    <other_name>Ribofluor</other_name>
    <other_name>Ro 2-9757</other_name>
    <other_name>Ro-2-9757</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <other_name>dFdC</other_name>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Control arm GroupI(mFOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupIII(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupV(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Control arm GroupI(mFOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupIII(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupV(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <other_name>Folinic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-paclitaxel</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <other_name>ABI 007</other_name>
    <other_name>ABI-007</other_name>
    <other_name>Abraxane</other_name>
    <other_name>Albumin-bound Paclitaxel</other_name>
    <other_name>Albumin-Stabilized Nanoparticle Paclitaxel</other_name>
    <other_name>Nanoparticle Albumin-bound Paclitaxel</other_name>
    <other_name>Nanoparticle Paclitaxel</other_name>
    <other_name>Paclitaxel Albumin</other_name>
    <other_name>paclitaxel albumin-stabilized nanoparticle formulation</other_name>
    <other_name>Protein-bound Paclitaxel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Control arm GroupI(mFOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupII(chemotherapy, FOLFIRINOX)</arm_group_label>
    <arm_group_label>Control arm GroupIII(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupV(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <other_name>1-OHP</other_name>
    <other_name>Ai Heng</other_name>
    <other_name>Aiheng</other_name>
    <other_name>Dacotin</other_name>
    <other_name>Dacplat</other_name>
    <other_name>Diaminocyclohexane Oxalatoplatinum</other_name>
    <other_name>Eloxatin</other_name>
    <other_name>Eloxatine</other_name>
    <other_name>JM-83</other_name>
    <other_name>Oxalatoplatin</other_name>
    <other_name>Oxalatoplatinum</other_name>
    <other_name>RP 54780</other_name>
    <other_name>RP-54780</other_name>
    <other_name>SR-96669</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Undergo RT</description>
    <arm_group_label>Control arm GroupIII(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupV(FOLFIRINOX, radiation therapy)</arm_group_label>
    <arm_group_label>Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)</arm_group_label>
    <other_name>Cancer Radiotherapy</other_name>
    <other_name>Irradiate</other_name>
    <other_name>Irradiated</other_name>
    <other_name>Irradiation</other_name>
    <other_name>Radiation</other_name>
    <other_name>Radiation Therapy, NOS</other_name>
    <other_name>Radiotherapeutics</other_name>
    <other_name>Radiotherapy</other_name>
    <other_name>RT</other_name>
    <other_name>Therapy, Radiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Pathologically proven adenocarcinoma of the&#xD;
             pancreas by cytology or biopsy&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Confirmation of clinical stage of resectable&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: No prior chemotherapy or radiation therapy for&#xD;
             PDAC&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: No current use of immunosuppressive medication&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Not pregnant and not nursing, for women of&#xD;
             childbearing potential, a negative urine or blood pregnancy test done =&lt; 7 days prior&#xD;
             to registration is required&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Life expectancy greater than 6 months&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Eastern Cooperative Oncology Group (ECOG)&#xD;
             performance status 0 or 1&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC) &gt;= 1,500/mm^3&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Creatinine =&lt; 1.5 x upper limit of normal&#xD;
             (ULN)&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Calculated (Calc.) creatinine clearance &gt; 45&#xD;
             mL/min&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Total bilirubin =&lt; 2.0 mg/dL&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Aspartate aminotransferase (AST)/alanine&#xD;
             aminotransferase (ALT) =&lt; 2.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Hemoglobin &gt;= 8.0 mg/dL&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Pathologically proven adenocarcinoma of the&#xD;
             pancreas by cytology or biopsy&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Confirmation of clinical stage of&#xD;
             resectable&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Prior chemotherapy for PDAC is allowed, as&#xD;
             long as the regimen is considered a standard regimen for PDAC (e.g., gemcitabine,&#xD;
             gemcitabine-cisplatin, gemcitabine/nab-paclitaxel, gemcitabine/capecitabine,&#xD;
             FOLFIRINOX). This should be discussed with the study principal investigators (PIs)&#xD;
             prior to enrollment to ensure the regimen for a given patient is acceptable&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: No current use of immunosuppressive&#xD;
             medication&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Not pregnant and not nursing, For women of&#xD;
             childbearing potential, a negative urine or blood pregnancy test done ≤ 7 days prior&#xD;
             to registration is required&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Life expectancy greater than 6 months&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: ECOG performance status 0 or 1&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC) &gt;=&#xD;
             1,500/mm^3&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Creatinine =&lt; 1.5 x upper limit of normal&#xD;
             (ULN)&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Calc. creatinine clearance &gt; 45 mL/min&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Total bilirubin =&lt; 2.0 mg/dL&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: AST/ALT =&lt; 2.5 x upper limit of normal&#xD;
             (ULN)&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Hemoglobin &gt;= 8.0 mg/dL&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Pathologically proven&#xD;
             adenocarcinoma of the pancreas by cytology or biopsy&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Confirmation of clinical stage of&#xD;
             borderline resectable&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: No prior chemotherapy or radiation&#xD;
             therapy for PDAC&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: No current use of immunosuppressive&#xD;
             medication&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Not pregnant and not nursing, For&#xD;
             women of childbearing potential, a negative urine or blood pregnancy test done ≤ 7&#xD;
             days prior to registration is required&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Life expectancy greater than 6&#xD;
             months&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: ECOG performance status 0 or 1&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC) &gt;=&#xD;
             1,500/mm^3&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Creatinine =&lt; 1.5 x upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Calc. creatinine clearance &gt; 45&#xD;
             mL/min&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Total bilirubin =&lt; 2.0 mg/dL&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: AST/ALT =&lt; 2.5 x upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Hemoglobin &gt;= 8.0 mg/dL&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Pathologically proven&#xD;
             adenocarcinoma of the pancreas by cytology or biopsy&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Confirmation of clinical stage&#xD;
             of borderline resectable&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Prior chemotherapy for PDAC is&#xD;
             allowed, as long as the regimen is considered a standard regimen for PDAC (e.g.,&#xD;
             gemcitabine, gemcitabine-cisplatin, gemcitabine/nab-paclitaxel,&#xD;
             gemcitabine/capecitabine, FOLFIRINOX). This should be discussed with the study PIs&#xD;
             prior to enrollment to ensure the regimen for a given patient is acceptable&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: No current use of&#xD;
             immunosuppressive medication&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Not pregnant and not nursing,&#xD;
             For women of childbearing potential, a negative urine or blood pregnancy test done =&lt;&#xD;
             7 days prior to registration is required&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Life expectancy greater than 6&#xD;
             months&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: ECOG performance status 0 or 1&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Absolute neutrophil count (ANC)&#xD;
             &gt;= 1,500/mm^3&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Creatinine =&lt; 1.5 x upper limit&#xD;
             of normal (ULN)&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Calc. creatinine clearance &gt; 45&#xD;
             mL/min&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Total bilirubin =&lt; 2.0 mg/dL&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: AST/ALT =&lt; 2.5 x upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  PREVIOUSLY TREATED BORDERLINE RESECTABLE PDAC COHORT: Hemoglobin &gt;= 8.0 mg/dL&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Pathologically proven adenocarcinoma of&#xD;
             the pancreas by cytology or biopsy&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Confirmation of clinical stage of&#xD;
             locally advanced&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: No prior chemotherapy or radiation&#xD;
             therapy for PDAC&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Pregnancy and Nursing Status: Not&#xD;
             pregnant and not nursing, For women of childbearing potential, a negative urine or&#xD;
             blood pregnancy test done ≤ 7 days prior to registration is required&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Life expectancy greater than 6 months&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: ECOG performance status 0 or 1&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Absolute neutrophil count (ANC) &gt;=&#xD;
             1,500/mm^3&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Creatinine =&lt; 1.5 x upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Calc. creatinine clearance &gt; 45 mL/min&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Total bilirubin =&lt; 2.0 mg/dL&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: AST/ALT =&lt; 2.5 x upper limit of normal&#xD;
             (ULN)&#xD;
&#xD;
          -  TREATMENT NAIVE LOCALLY ADVANCED PDAC COHORT: Hemoglobin &gt;= 8.0 mg/dL&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Pathologically proven adenocarcinoma&#xD;
             of the pancreas by cytology or biopsy&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Confirmation of clinical stage of&#xD;
             locally advanced&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Prior chemotherapy for PDAC is&#xD;
             allowed, as long as the regimen is considered a standard regimen for PDAC (e.g.,&#xD;
             gemcitabine, gemcitabine-cisplatin, gemcitabine/nab-paclitaxel,&#xD;
             gemcitabine/capecitabine, FOLFIRINOX). This should be discussed with the study PIs&#xD;
             prior to enrollment to ensure the regimen for a given patient is acceptable&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: No current use of immunosuppressive&#xD;
             medication&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Not pregnant and not nursing, For&#xD;
             women of childbearing potential, a negative urine or blood pregnancy test done =&lt; 7&#xD;
             days prior to registration is required&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Life expectancy greater than 6 months&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: ECOG performance status 0 or 1&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Absolute neutrophil count (ANC) &gt;=&#xD;
             1,500/mm^3&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Platelet count &gt;= 100,000/mm^3&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Creatinine =&lt; 1.5 x upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Calc. creatinine clearance &gt; 45&#xD;
             mL/min&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Total bilirubin =&lt; 2.0 mg/dL&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: AST/ALT =&lt; 2.5 x upper limit of&#xD;
             normal (ULN)&#xD;
&#xD;
          -  PREVIOUSLY TREATED LOCALLY ADVANCED PDAC COHORT: Hemoglobin &gt;= 8.0 mg/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Previous treatment for PDAC with chemotherapy&#xD;
             or radiation&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Active malignancy, except basal cell carcinoma&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Staging other than resectable PDAC&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Known uncontrolled (grade &gt;=2) or active&#xD;
             gastric or duodenal ulcer disease within 30 days of enrollment&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Prior surgical resection of pancreatic tumor&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Known contraindication to iodine-based or&#xD;
             gadolinium-based intravenous (IV) contrast&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Clinically significant cardiac arrhythmias&#xD;
             (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second&#xD;
             or third degree atrioventricular heart block without a permanent pacemaker in place)&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Class III or IV congestive heart failure as&#xD;
             defined by the New York Heart Association functional classification system &lt; 6 months&#xD;
             prior to screening&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Known active, uncontrolled (high viral load)&#xD;
             human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection&#xD;
&#xD;
               -  Patients who have been vaccinated for hepatitis B and do not have a history of&#xD;
                  infection are eligible&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Female patients who are pregnant of&#xD;
             breastfeeding&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Women of child-bearing potential and their&#xD;
             male partners who are unwilling or unable to use an acceptable method of birth control&#xD;
             to avoid pregnancy for the entire study period. Acceptable methods of contraception&#xD;
             are those that, alone or in combination, result in a failure rate of &lt; 1% per year&#xD;
             when used consistently and correctly&#xD;
&#xD;
          -  TREATMENT NAIVE RESECTABLE PDAC COHORT: Have significant psychiatric, social, or&#xD;
             medical condition(s) that could increase the subject's risk, interfere with protocol&#xD;
             adherence, or affect the subject's ability to give informed consent&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: The patient is treatment naive&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: The patient previously received radiation&#xD;
             to the abdomen for any reason&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Active malignancy, except basal cell&#xD;
             carcinoma&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Staging other than resectable PDAC at the&#xD;
             time of diagnosis&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Receiving any approved or investigational&#xD;
             anti-neoplastic agent other than the chemotherapies specified in this protocol&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Known uncontrolled (grade &gt;= 2) or active&#xD;
             gastric or duodenal ulcer disease within 30 days of enrollment&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Prior surgical resection of pancreatic&#xD;
             tumor&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Known contraindication to iodine-based or&#xD;
             gadolinium-based IV contrast&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Clinically significant cardiac arrhythmias&#xD;
             (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second&#xD;
             or third degree atrioventricular heart block without a permanent pacemaker in place)&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Class III or IV congestive heart failure as&#xD;
             defined by the New York Heart Association functional classification system &lt; 6 months&#xD;
             prior to screening&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Known active, uncontrolled (high viral&#xD;
             load) HIV, hepatitis B or hepatitis C infection&#xD;
&#xD;
               -  Patients who have been vaccinated for hepatitis B and do not have a history of&#xD;
                  infection are eligible&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Female patients who are pregnant of&#xD;
             breastfeeding&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Women of child-bearing potential and their&#xD;
             male partners who are unwilling or unable to use an acceptable method of birth control&#xD;
             to avoid pregnancy for the entire study period. Acceptable methods of contraception&#xD;
             are those that, alone or in combination, result in a failure rate of &lt; 1% per year&#xD;
             when used consistently and correctly&#xD;
&#xD;
          -  PREVIOUSLY TREATED RESECTABLE PDAC COHORT: Have significant psychiatric, social, or&#xD;
             medical condition(s) that could increase the subject's risk, interfere with protocol&#xD;
             adherence, or affect the subject's ability to give informed consent&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Previous treatment for PDAC with&#xD;
             chemotherapy or radiation&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Active malignancy, except basal&#xD;
             cell carcinoma&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Staging other than borderline&#xD;
             resectable PDAC&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Known uncontrolled (grade &gt;= 2) or&#xD;
             active gastric or duodenal ulcer disease within 30 days of enrollment&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Prior surgical resection of&#xD;
             pancreatic tumor&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Known contraindication to&#xD;
             iodine-based or gadolinium-based IV contrast&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Clinically significant cardiac&#xD;
             arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de&#xD;
             pointes, second or third degree atrioventricular heart block without a permanent&#xD;
             pacemaker in place)&#xD;
&#xD;
          -  TREATMENT NAIVE BORDERLINE RESECTABLE PDAC COHORT: Class III or IV congestive hea&#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>Eugene J Koay</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>M D Anderson Cancer Center</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</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>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <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/NCT04481204
org study id: 2020-0075
secondary id: NCI-2020-04886
secondary id: 2020-0075
nct id: NCT04481204
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase II study using the Bayesian platform design. There are three clinical stage
      groups of localized pancreatic cancer: resectable, borderline resectable, and locally
      advanced disease. Each stage group will have a defined standard of care chemotherapy regimen
      for a control arm, serving as a basis of comparison. Each group may have one or more
      experimental arms. Experimental arms may be added to the platform over time, and the effects
      of the experimental treatments will be tested against the controls for each group.
PRIMARY OBJECTIVES:

      I. To estimate major pathological response rate. (Resectable and borderline resectable groups
      [treatment naive or previously treated]) II. To estimate 6-month disease control rate.
      (Locally advanced groups [treatment naive or previously treated])

      SECONDARY OBJECTIVES:

      I. To measure progression free survival and overall survival. (Resectable and borderline
      resectable groups [treatment naive or previously treated]) II. To measure progression free
      survival and overall survival. (Locally advanced groups [treatment naive or previously
      treated])

      EXPLORATORY OBJECTIVES:

      I. To benchmark tissue acquisition protocols for deoxyribonucleic acid (DNA) and ribonucleic
      acid (RNA) analysis in pancreatic ductal adenocarcinoma (PDAC).

      II. To demonstrate concordance of cell free DNA detected mutations to those detected in the
      tumor-derived DNA in PDAC.

      III. To demonstrate response through exosome and circulating tumor DNA. IV. To demonstrate
      response through the quantification of the immune activation by analyzing T and B cells,
      peripheral blood mononuclear cells, and tissue biopsies.

      V. To derive organoids from human PDAC and measure drug response in vitro. VI. To analyze the
      tumor microenvironment through immunohistochemistry (IHC) and hypoxia staining.

      VII. To associate prognosis of patients with baseline and follow-up quantitative computed
      tomography (CT) image based analysis.

      VIII. To associate clinical and pathological outcomes of patients with changes in radiomic
      measurements.

      IX. To correlate quality of life for patients on standard and experimental therapies with
      laboratory, radiological, pathological, and clinical characteristics.

      OUTLINE:Patients are assigned to different groups, and each group has a control arm. Within
      each group, the patient will be randomized to the appropriate control or an experimental arm.
      The control arms for the groups are:

      Control arm for Group I (Treatment-naive resectable PDAC): Patients receive fluorouracil,
      irinotecan, leucovorin, and oxaliplatin (mFOLFIRINOX) for 3 months before and after surgery
      in the absence of disease progression or unacceptable toxicity.

      Control arm for Group II (Previously-treated resectable PDAC): Patients receive gemcitabine,
      gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months
      in the absence of disease progression or unacceptable toxicity.

      Control arm for Group III (Treatment-naive borderline resectable PDAC): Patients receive
      FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity.
      Patients may then undergo radiation therapy at the discretion of medical doctors.

      Control arm for Group IV (Previously-treated borderline resectable PDAC): Patients receive
      gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6
      months in the absence of disease progression or unacceptable toxicity. Patients may then
      undergo radiation therapy at the discretion of medical doctors.

      Control arm for Group V (Treatment-naive locally advanced PDAC): Patients receive FOLFIRINOX
      for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may
      then undergo radiation therapy at the discretion of medical doctors.

      Control arm for Group VI (Previously-treated locally advanced PDAC): Patients receive
      gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6
      months in the absence of disease progression or unacceptable toxicity. Patients may then
      undergo radiation therapy at the discretion of medical doctors.

      After completion of study treatment, patients are followed up every 16 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Major pathological response rate
time frame: 12 weeks
description: Major pathological response is any patient who has grade I or II treatment response. Grade I - 0% residual tumor cells in the specimen (pathologic complete response, grade II - 1 to < 5% residual tumor cells in the specimen.
measure: Disease control rate
time frame: 6 months
description: Measured as the proportion of patients without progression.
measure: Progression free survival
time frame: From the date of treatment initiation to the date of disease progression, recurrence after surgery or death from any cause whichever occurs first, assessed up to 5 years
description: Will be estimated using the Kaplan-Meier method. Comparisons of these time-to-event endpoints by important covariate subgroups will be made using the log-rank tests. Cox proportional hazards regression models will be explored to evaluate the associations between the time-to-event endpoints and covariates of interest.
measure: Overall survival
time frame: From treatment start till death or last follow-up if the patient is alive, assessed up to 5 years
description: Will be estimated using the Kaplan-Meier method. Comparisons of these time-to-event endpoints by important covariate subgroups will be made using the log-rank tests. Cox proportional hazards regression models will be explored to evaluate the associations between the time-to-event endpoints and covariates of interest.
arm group label: Control arm GroupI(mFOLFIRINOX)
arm group type: Active Comparator
description: Patients receive mFOLFIRINOX for 3 months before and after surgery in the absence of disease progression or unacceptable toxicity.
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group type: Active Comparator
description: Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months in the absence of disease progression or unacceptable toxicity.
arm group label: Control arm GroupIII(FOLFIRINOX, radiation therapy)
arm group type: Active Comparator
description: Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group type: Active Comparator
description: Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.
arm group label: Control arm GroupV(FOLFIRINOX, radiation therapy)
arm group type: Active Comparator
description: Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
arm group type: Active Comparator
description: Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors
intervention type: Drug
intervention name: Cisplatin
description: Given IV
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
other name: Abiplatin
other name: Blastolem
other name: Briplatin
other name: CDDP
other name: Cis-diammine-dichloroplatinum
other name: Cis-diamminedichloridoplatinum
other name: Cis-diamminedichloro Platinum (II)
other name: Cis-diamminedichloroplatinum
other name: Cis-dichloroammine Platinum (II)
other name: Cis-platinous Diamine Dichloride
other name: Cis-platinum
other name: Cis-platinum II
other name: Cis-platinum II Diamine Dichloride
other name: Cismaplat
other name: Cisplatina
other name: Cisplatinum
other name: Cisplatyl
other name: Citoplatino
other name: Citosin
other name: Cysplatyna
other name: DDP
other name: Lederplatin
other name: Metaplatin
other name: Neoplatin
other name: Peyrone''s Chloride
other name: Peyrone''s Salt
other name: Placis
other name: Plastistil
other name: Platamine
other name: Platiblastin
other name: Platiblastin-S
other name: Platinex
other name: Platinol
other name: Platinol- AQ
other name: Platinol-AQ
other name: Platinol-AQ VHA Plus
other name: Platinoxan
other name: Platinum
other name: Platinum Diamminodichloride
other name: Platiran
other name: Platistin
other name: Platosin
intervention type: Drug
intervention name: Fluorouracil
description: Given IV
arm group label: Control arm GroupI(mFOLFIRINOX)
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group label: Control arm GroupIII(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupV(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
other name: 5 Fluorouracil
other name: 5 Fluorouracilum
other name: 5 FU
other name: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
other name: 5-Fluorouracil
other name: 5-Fluracil
other name: 5-Fu
other name: 5FU
other name: AccuSite
other name: Carac
other name: Fluoro Uracil
other name: Fluouracil
other name: Flurablastin
other name: Fluracedyl
other name: Fluracil
other name: Fluril
other name: Fluroblastin
other name: Ribofluor
other name: Ro 2-9757
other name: Ro-2-9757
intervention type: Drug
intervention name: Gemcitabine
description: Given IV
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
other name: dFdC
other name: dFdCyd
other name: Difluorodeoxycytidine
intervention type: Drug
intervention name: Irinotecan
description: Given IV
arm group label: Control arm GroupI(mFOLFIRINOX)
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group label: Control arm GroupIII(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupV(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
intervention type: Drug
intervention name: Leucovorin
description: Given IV
arm group label: Control arm GroupI(mFOLFIRINOX)
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group label: Control arm GroupIII(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupV(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
other name: Folinic acid
intervention type: Drug
intervention name: Nab-paclitaxel
description: Given IV
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
other name: ABI 007
other name: ABI-007
other name: Abraxane
other name: Albumin-bound Paclitaxel
other name: Albumin-Stabilized Nanoparticle Paclitaxel
other name: Nanoparticle Albumin-bound Paclitaxel
other name: Nanoparticle Paclitaxel
other name: Paclitaxel Albumin
other name: paclitaxel albumin-stabilized nanoparticle formulation
other name: Protein-bound Paclitaxel
intervention type: Drug
intervention name: Oxaliplatin
description: Given IV
arm group label: Control arm GroupI(mFOLFIRINOX)
arm group label: Control arm GroupII(chemotherapy, FOLFIRINOX)
arm group label: Control arm GroupIII(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupV(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
other name: 1-OHP
other name: Ai Heng
other name: Aiheng
other name: Dacotin
other name: Dacplat
other name: Diaminocyclohexane Oxalatoplatinum
other name: Eloxatin
other name: Eloxatine
other name: JM-83
other name: Oxalatoplatin
other name: Oxalatoplatinum
other name: RP 54780
other name: RP-54780
other name: SR-96669
intervention type: Radiation
intervention name: Radiation Therapy
description: Undergo RT
arm group label: Control arm GroupIII(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy)
arm group label: Control arm GroupV(FOLFIRINOX, radiation therapy)
arm group label: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy)
other name: Cancer Radiotherapy
other name: Irradiate
other name: Irradiated
other name: Irradiation
other name: Radiation
other name: Radiation Therapy, NOS
other name: Radiotherapeutics
other name: Radiotherapy
other name: RT
other name: Therapy, Radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eugene J Koay
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: M D Anderson Cancer Center
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Cisplatin
mesh term: Gemcitabine
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Irinotecan