<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/NCT03038477</url>
  </required_header>
  <id_info>
    <org_study_id>16-0546.cc</org_study_id>
    <nct_id>NCT03038477</nct_id>
  </id_info>
  <brief_title>A Study of Durvalumab in Patients With BR PDA Following Neoadjuvant Therapy and Successful Surgical Resection</brief_title>
  <official_title>A Study of Durvalumab (MEDI4736), as an Adjuvant Therapy, Compared to Observation Alone, in Patients With Borderline Resectable Pancreatic Ductal Adenocarcinoma (BR PDA) Following Neoadjuvant Therapy and Successful Surgical Resection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</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 two-arm, open-label, phase II study of in adult patients who have successfully&#xD;
      undergone R0/R1 resection of PDAs following neoadjuvant chemotherapy and completion of&#xD;
      adjuvant chemotherapy. Within 1-3 months of treatment completion, patients will be enrolled&#xD;
      and randomized at a 1:1 ratio to receive durvalumab versus observation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Borderline resectable pancreatic cancer (BRPC) patients who have successfully underwent R0/R1&#xD;
      resection of PDAs following neoadjuvant chemotherapy, between 1-3 months after the completion&#xD;
      of planned adjuvant chemotherapy will be enrolled and randomized at a 1:1 ratio into two arms&#xD;
      (56 per arm). Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks&#xD;
      for a maximum of 26 doses if there is no radiographic evidence of disease recurrence.&#xD;
      Patients in Arm B will be observed. Blood draws for immune monitoring and serum banking will&#xD;
      be collected at the following time points:&#xD;
&#xD;
      Arm A - before Cycles 1, 2, 4, 7 and End of Treatment (EOT) visit; Arm B - before Cycles 1,&#xD;
      4, 7, and End of Treatment (EOT) visit&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Cancelled by PI&#xD;
  </why_stopped>
  <start_date type="Actual">June 12, 2017</start_date>
  <completion_date type="Actual">April 1, 2019</completion_date>
  <primary_completion_date type="Actual">April 1, 2019</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>The number of subjects with disease free survival (DFS)</measure>
    <time_frame>26 Months</time_frame>
    <description>Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) of all patients</measure>
    <time_frame>26 months</time_frame>
    <description>OS is defined as the time from study enrollment to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of patients who experience adverse events</measure>
    <time_frame>26 months</time_frame>
    <description>Adverse events are measured by Common Terminology Criteria for Adverse Events (CTCAE v4.03).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Durvalumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks for a maximum of 26 doses if there is no radiographic evidence of disease recurrence. For Arm A, one cycle constitutes two durvalumab treatments on Day 1 and Day 15, respectively, repeated every 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Durvalumab</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients in Arm B will be observed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>1500mg of Durvalumab will be given every 4 weeks (Q4W) for 12 months in patients enrolled in Arm A.</description>
    <arm_group_label>Durvalumab</arm_group_label>
    <other_name>MEDI4736</other_name>
    <other_name>anti-PD-L1 antibody</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent and any locally-required authorization (e.g., HIPAA in the&#xD;
             USA, EU Data Privacy Directive in the EU) obtained from the subject prior to&#xD;
             performing any protocol-related procedures, including screening evaluations&#xD;
&#xD;
          2. Age &gt; 18 years at time of study entry, age &gt; 20 years for Japanese subjects.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          4. Life expectancy of &gt; 2 years&#xD;
&#xD;
          5. Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Haemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (&gt; 1500 per mm3)&#xD;
&#xD;
               -  Absolute lymphocyte count ≥ 500/mm3&#xD;
&#xD;
               -  Platelet count ≥ 100 x 109/L (&gt;100,000 per mm3)&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). &lt;&lt;This will&#xD;
                  not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent&#xD;
                  hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis&#xD;
                  or hepatic pathology), who will be allowed only in consultation with their&#xD;
                  physician.&gt;&gt;&#xD;
&#xD;
               -  AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver&#xD;
                  metastases are present, in which case it must be ≤ 5x ULN&#xD;
&#xD;
               -  Serum creatinine CL&gt;40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault&#xD;
                  1976) or by 24-hour urine collection for determination of creatinine clearance:&#xD;
&#xD;
             Males:&#xD;
&#xD;
             Creatinine CL (mL/min) = (Weight (kg) x (140 - Age)) / (72 x serum creatinine (mg/dL))&#xD;
&#xD;
             Females:&#xD;
&#xD;
             Creatinine CL (mL/min) = (Weight (kg) x (140 - Age)) / (72 x serum creatinine (mg/dL))&#xD;
             x0.85&#xD;
&#xD;
          6. Women must either be of non-reproductive potential (ie, post-menopausal by history:&#xD;
             ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR&#xD;
             history of hysterectomy, OR history of bilateral tubal ligation, OR history of&#xD;
             bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry&#xD;
             (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin&#xD;
             [HCG]).&#xD;
&#xD;
          7. Both women of childbearing potential (WOCBP) and men who are sexually active with&#xD;
             WOCBP must agree to use two (2) highly effective methods of contraception as outlined&#xD;
             in this protocol for the duration of treatment with study drug plus 5 half-lives of&#xD;
             study drug plus 90 days (duration of sperm turnover) for a total of 31 weeks&#xD;
             post-treatment completion.&#xD;
&#xD;
          8. Subject is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#xD;
&#xD;
          9. Have borderline resectable PDAs at the time of original diagnosis as per the AHPBA/SSO&#xD;
             consensus on definition of borderline resectable PDA (see section 4.4 for definition&#xD;
             of borderline resectable PDAs).&#xD;
&#xD;
         10. Have had an R0/R1 resection of PDA following neoadjuvant chemotherapy.&#xD;
&#xD;
         11. Have been more than one month and less than 3 months after the completion of planned&#xD;
             adjuvant chemotherapy.&#xD;
&#xD;
         12. Have received at least one treatment of either FOLFIRINOX or gemcitabine/abraxane&#xD;
             based regimens in both neoadjuvant and adjuvant setting. Neoadjuvant radiation is&#xD;
             allowed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at the study site). Previous enrollment in the present study&#xD;
&#xD;
          2. Participation in another clinical study with an investigational product during the&#xD;
             last 4 weeks.&#xD;
&#xD;
          3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.&#xD;
&#xD;
          4. History of another primary malignancy except for:&#xD;
&#xD;
               1. Malignancy treated with curative intent and with no known active disease ≥5 years&#xD;
                  before the first dose of study drug and of low potential risk for recurrence&#xD;
&#xD;
               2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
               3. Adequately treated carcinoma in situ without evidence of disease eg, cervical&#xD;
                  cancer in situ&#xD;
&#xD;
          5. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,&#xD;
             endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal&#xD;
             antibodies, other investigational agent) ≤ 28 days prior to the first dose of study&#xD;
             drug (≤ 28 days prior to the first dose of study drug for subjects who have received&#xD;
             prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for&#xD;
             nitrosourea or mitomycin C). (If sufficient wash-out time has not occurred due to the&#xD;
             schedule or PK properties of an agent, a longer wash-out period may be required.)&#xD;
&#xD;
          6. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3&#xD;
             electrocardiograms (ECGs) using Frediricia's Correction&#xD;
&#xD;
          7. Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or&#xD;
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of&#xD;
             prednisone, or an equivalent corticosteroid&#xD;
&#xD;
          8. Any unresolved toxicity (&gt;CTCAE grade 2) from previous anti-cancer therapy. Subjects&#xD;
             with irreversible toxicity that is not reasonably expected to be exacerbated by the&#xD;
             investigational product may be included (e.g., hearing loss, peripherally neuropathy).&#xD;
&#xD;
          9. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous&#xD;
             immunotherapy agent, or any unresolved irAE &gt;Grade 1&#xD;
&#xD;
         10. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects&#xD;
             with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within&#xD;
             the past 2 years) are not excluded.&#xD;
&#xD;
         11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,&#xD;
             ulcerative colitis)&#xD;
&#xD;
         12. History of primary immunodeficiency&#xD;
&#xD;
         13. History of allogeneic organ transplant&#xD;
&#xD;
         14. History of hypersensitivity to durvalumab or any excipient&#xD;
&#xD;
         15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable&#xD;
             angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active&#xD;
             bleeding diatheses including any subject known to have evidence of acute or chronic&#xD;
             hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirements or&#xD;
             compromise the ability of the subject to give written informed consent&#xD;
&#xD;
         16. Known history of previous clinical diagnosis of tuberculosis&#xD;
&#xD;
         17. History of leptomeningeal carcinomatosis&#xD;
&#xD;
         18. Receipt of live attenuated vaccination within 30 days prior to study entry or within&#xD;
             30 days of receiving durvalumab&#xD;
&#xD;
         19. Female subjects who are pregnant, breast-feeding or male or female patients of&#xD;
             reproductive potential who are not employing an effective method of birth control&#xD;
&#xD;
         20. Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of study treatment or interpretation of patient safety or study results.&#xD;
&#xD;
         21. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive&#xD;
             of but not limited to surgery, radiation and/or corticosteroids.&#xD;
&#xD;
         22. Subjects with uncontrolled seizures.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>101 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wells Messersmith, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>September 10, 2020</last_update_submitted>
  <last_update_submitted_qc>September 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Borderline Resectable Pancreatic Ductal Adenocarcinoma</keyword>
  <keyword>Durvalumab</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</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/NCT03038477
org study id: 16-0546.cc
nct id: NCT03038477
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a two-arm, open-label, phase II study of in adult patients who have successfully
      undergone R0/R1 resection of PDAs following neoadjuvant chemotherapy and completion of
      adjuvant chemotherapy. Within 1-3 months of treatment completion, patients will be enrolled
      and randomized at a 1:1 ratio to receive durvalumab versus observation.
Borderline resectable pancreatic cancer (BRPC) patients who have successfully underwent R0/R1
      resection of PDAs following neoadjuvant chemotherapy, between 1-3 months after the completion
      of planned adjuvant chemotherapy will be enrolled and randomized at a 1:1 ratio into two arms
      (56 per arm). Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks
      for a maximum of 26 doses if there is no radiographic evidence of disease recurrence.
      Patients in Arm B will be observed. Blood draws for immune monitoring and serum banking will
      be collected at the following time points:

      Arm A - before Cycles 1, 2, 4, 7 and End of Treatment (EOT) visit; Arm B - before Cycles 1,
      4, 7, and End of Treatment (EOT) visit
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The number of subjects with disease free survival (DFS)
time frame: 26 Months
description: Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause.
measure: Overall survival (OS) of all patients
time frame: 26 months
description: OS is defined as the time from study enrollment to death from any cause.
measure: The number of patients who experience adverse events
time frame: 26 months
description: Adverse events are measured by Common Terminology Criteria for Adverse Events (CTCAE v4.03).
arm group label: Durvalumab
arm group type: Experimental
description: Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks for a maximum of 26 doses if there is no radiographic evidence of disease recurrence. For Arm A, one cycle constitutes two durvalumab treatments on Day 1 and Day 15, respectively, repeated every 28 days.
arm group label: No Durvalumab
arm group type: No Intervention
description: Patients in Arm B will be observed.
intervention type: Drug
intervention name: Durvalumab
description: 1500mg of Durvalumab will be given every 4 weeks (Q4W) for 12 months in patients enrolled in Arm A.
arm group label: Durvalumab
other name: MEDI4736
other name: anti-PD-L1 antibody
criteria: 
gender: All
minimum age: 18 Years
maximum age: 101 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wells Messersmith, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
responsible party type: Sponsor
mesh term: Durvalumab
sharing ipd: No