<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/NCT03245541</url>
  </required_header>
  <id_info>
    <org_study_id>20-228</org_study_id>
    <nct_id>NCT03245541</nct_id>
  </id_info>
  <brief_title>Radiation Therapy in Combination With Durvalumab for People With Pancreatic Cancer</brief_title>
  <official_title>A Phase I/II Study of Durvalumab (Medi 4736) and Stereotactic Ablative Body Radiotherapy in Locally Advanced Pancreatic Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cedars-Sinai Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out if combining durvalumab with standard stereotactic&#xD;
      ablative radiotherapy (SABR) is an effective treatment for people with locally advanced or&#xD;
      borderline resectable pancreatic cancer. The researchers will also look at the safety of the&#xD;
      combination treatment and any side effects it causes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with dose limiting toxicities in the first 10 weeks of treatment</measure>
    <time_frame>10 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>12 months</time_frame>
    <description>Duration of time from diagnosis to time of progression</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of participants who have resectable disease</measure>
    <time_frame>24 weeks</time_frame>
    <description>Based on overall downstaging of disease post-treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression Free Survival (Phase II)</measure>
    <time_frame>6 months</time_frame>
    <description>From study enrollment to time of progression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change in levels of inflammatory cytokines from baseline</measure>
    <time_frame>10 weeks</time_frame>
    <description>As measured from cytokine analysis from serum</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in levels of immune cells from baseline</measure>
    <time_frame>10 weeks</time_frame>
    <description>As determined from flow cytometry from biopsies and blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in protein levels from baseline</measure>
    <time_frame>10 weeks</time_frame>
    <description>As determined from quantitative immunohistochemistry on biopsy samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in microbiome from baseline</measure>
    <time_frame>10 weeks</time_frame>
    <description>As determined from analysis of stool samples</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Pancreatic Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Durvalumab + SABR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab + Stereotactic Ablative Body Radiotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab will be given 750 mg, intravenously (IV) over 60 minutes (+/- 5 minutes), Q14 days beginning D1. Four doses of durvalumab will be administered on the Q14 day schedule. Subsequently Durvalumab will continue as maintenance 1500mg, intravenously (IV) over 60 minutes (+/- 5 minutes), Q28 days up to 1 year or until progression (11 doses), unacceptable toxicity or other reason. If a patient undergoes resection, they will resume durvalumab once appropriately healed from surgery (approximately 4-8 weeks) at discretion of treating medical oncologist.</description>
    <arm_group_label>Durvalumab + SABR</arm_group_label>
    <other_name>Medi 4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic Ablative Body Radiotherapy (SABR)</intervention_name>
    <description>SABR delivered as 6.6 Gy/fraction x 5 fractions given within two weeks will be administered weekdays and will begin D8.</description>
    <arm_group_label>Durvalumab + SABR</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histopathologic or cytologic diagnosis of adenocarcinoma of the pancreas&#xD;
             (PDAC), or suspicious for malignancy per pathology, which is deemed BR or LA PDAC per&#xD;
             NCCN guidelines or following evaluation by a Multidisciplinary group of physicians.&#xD;
&#xD;
          -  Patients must have received FOLFIRINOX for 3-6 months prior to enrollment with at&#xD;
             least stable disease by restaging imaging.&#xD;
&#xD;
        Note: SOC treatment regimen derived from FOLFIRINOX dose modifications are acceptable.&#xD;
&#xD;
        To maximize potential efficacy no more than a 6-week treatment break is recommended between&#xD;
        the completion of SOC chemotherapy (FOLFIRINOX) and initiation of study treatment&#xD;
        (durvalumab).&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Body weight &gt;30kg&#xD;
&#xD;
          -  ECOG 0-2&#xD;
&#xD;
          -  Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute Neutrophil Count (ANC) ≥1.0 K/mcL&#xD;
&#xD;
               -  Platelets ≥75 K/mcL&#xD;
&#xD;
               -  Hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 X upper limit of normal (ULN)&#xD;
&#xD;
               -  AST(SGOT) and ALT(SGPT) ≤ 2.5 X ULN&#xD;
&#xD;
               -  Creatinine OR creatinine clearance ≤ 1.5 times the upper limit of normal OR &gt; 40&#xD;
                  mL/min for patients with creatinine levels above normal.&#xD;
&#xD;
        Note: Patients with biliary stent are eligible provided that all other inclusion criteria&#xD;
        are met.&#xD;
&#xD;
          -  Negative pregnancy test in women of childbearing potential (WOCBP) within 30 days of&#xD;
             durvalumab administration or evidence of post-menopausal status. Women will be&#xD;
             considered post-menopausal if they have been amenorrhoeic for 12 months without an&#xD;
             alternative medical cause or underwent surgical sterilization (bilateral oophorectomy&#xD;
             or hysterectomy).&#xD;
&#xD;
          -  Non-sterilized male participants who are sexually active with a female partner of&#xD;
             childbearing potential must be willing to use a highly effective method of&#xD;
             contraception from Day 1 through 90 days after receipt of the final dose of&#xD;
             investigational product(s). Not engaging in sexual activity for the total duration of&#xD;
             the study and the drug washout period is an acceptable practice; however, occasional&#xD;
             abstinence, the rhythm method, and the withdrawal method are not acceptable methods of&#xD;
             contraception. Male participants must be willing to refrain from sperm donation&#xD;
             throughout these periods.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign an informed consent document.&#xD;
&#xD;
          -  Willingness and ability to comply with the protocol including study treatment,&#xD;
             scheduled assessments and follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of another primary malignancy except for:&#xD;
&#xD;
             °Malignancy treated with curative intent with no known active disease for 2 years&#xD;
             before the first dose of study drug and low potential risk for recurrence.&#xD;
&#xD;
          -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of&#xD;
             disease&#xD;
&#xD;
          -  Patients who have had prior anti-cancer treatment or are currently receiving&#xD;
             anti-cancer treatment for their disease other than chemotherapy as stipulated by&#xD;
             protocol.&#xD;
&#xD;
          -  Women who are breastfeeding.&#xD;
&#xD;
          -  Any clinically significant, unresolved toxicity &gt;CTCAE grade 2 from previous&#xD;
             anti-cancer therapy with the exception of alopecia, vitiligo and laboratory values&#xD;
             defined in the inclusion criteria.&#xD;
&#xD;
          -  Patients with Grade ≥ 2 neuropathy will be included at the investigator's discretion&#xD;
&#xD;
          -  Patients with irreversible toxicity not reasonably expected to be exacerbated by&#xD;
             treatment with durvalumab may be included at the nvestigator's discretion&#xD;
&#xD;
          -  Patients who are currently receiving any other investigational agents for therapeutic&#xD;
             treatment of their primary cancer.&#xD;
&#xD;
          -  Any previous treatment with a PD1 or PD-L1 inhibitor, including Durvalumab or other&#xD;
             immunotherapy.&#xD;
&#xD;
          -  Known metastatic disease.&#xD;
&#xD;
          -  Major surgical procedures based on clinical judgement of the investigator within 30&#xD;
             days prior to the first dose of study drug. Patients may undergo staging laparoscopy,&#xD;
             PTC placement, ERCP, etc. at any time which should not interfere with study treatment.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to durvalumab.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, interstitial lung disease, pneumonitis, symptomatic congestive heart&#xD;
             failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirements.&#xD;
&#xD;
          -  Patients who are receiving radiation treatment outside of the enrolling centers.&#xD;
&#xD;
          -  Patients with frank transmural macroscopic invasion of duodenum by tumor as determined&#xD;
             by treating investigator.&#xD;
&#xD;
          -  Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis with the&#xD;
             exception of diverticulosis, celiac disease, irritable bowel syndrome, or other&#xD;
             serious gastrointestinal chronic conditions associated with diarrhea); systemic lupus&#xD;
             erythematosus; Wegener syndrome (granulomatosis with polyangiitis; Graves' disease;&#xD;
             rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 3 years prior to the&#xD;
             start of treatment. The following are exceptions to this criterion: Patients with&#xD;
             vitiligo or alopecia. Patients with hypothyroidism (e.g., following Hashimoto&#xD;
             syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 28 days before treatment,&#xD;
             except with chemotherapy.&#xD;
&#xD;
          -  History of organ transplant that requires use of immunosuppressive agents.&#xD;
&#xD;
          -  History of active primary immunodeficiency.&#xD;
&#xD;
          -  Receipt of live attenuated vaccination within 30 days prior to receiving durvalumab.&#xD;
&#xD;
          -  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;
          -  Active infection including tuberculosis (clinical evaluation that includes clinical&#xD;
             history, physical examination and radiographic findings and TB testing in line with&#xD;
             local practices), active bleeding diatheses, hepatitis B (known positive HBV surface&#xD;
             antigen result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2&#xD;
             antibodies).&#xD;
&#xD;
          -  Patient with known active Hepatitis (i.e. Hepatitis B or C).&#xD;
&#xD;
               -  Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen&#xD;
                  (HBsAg) result. Patients with a past or resolved HBV infection (defined as the&#xD;
                  presence of hepatitis B core antibody and absence of HBsAg and PCR negative) are&#xD;
                  eligible.&#xD;
&#xD;
               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if&#xD;
                  polymerase chain reaction is negative for HCV RNA.&#xD;
&#xD;
          -  Patients with macroscopic invasion of the bowel or stomach submucosa by primary&#xD;
             pancreatic tumor as determined by PI.&#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>Eileen O'Reilly, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (Limited Protocol Activities)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (Limited Protocol Activities)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack (Limited Protocol Activities)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (All Protocol Activities)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center (All Protocol Activities)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (Limited Protocol Activities)</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>August 10, 2023</last_update_submitted>
  <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stereotactic Ablative Body Radiotherapy (SABR)</keyword>
  <keyword>Durvalumab</keyword>
  <keyword>20-228</keyword>
  <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>Durvalumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </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/NCT03245541
org study id: 20-228
nct id: NCT03245541
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to find out if combining durvalumab with standard stereotactic
      ablative radiotherapy (SABR) is an effective treatment for people with locally advanced or
      borderline resectable pancreatic cancer. The researchers will also look at the safety of the
      combination treatment and any side effects it causes.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with dose limiting toxicities in the first 10 weeks of treatment
time frame: 10 weeks
measure: Progression Free Survival
time frame: 12 months
description: Duration of time from diagnosis to time of progression
measure: Proportion of participants who have resectable disease
time frame: 24 weeks
description: Based on overall downstaging of disease post-treatment
measure: Progression Free Survival (Phase II)
time frame: 6 months
description: From study enrollment to time of progression
measure: Mean change in levels of inflammatory cytokines from baseline
time frame: 10 weeks
description: As measured from cytokine analysis from serum
measure: Mean change in levels of immune cells from baseline
time frame: 10 weeks
description: As determined from flow cytometry from biopsies and blood
measure: Mean change in protein levels from baseline
time frame: 10 weeks
description: As determined from quantitative immunohistochemistry on biopsy samples
measure: Mean change in microbiome from baseline
time frame: 10 weeks
description: As determined from analysis of stool samples
arm group label: Durvalumab + SABR
arm group type: Experimental
description: Durvalumab + Stereotactic Ablative Body Radiotherapy
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab will be given 750 mg, intravenously (IV) over 60 minutes (+/- 5 minutes), Q14 days beginning D1. Four doses of durvalumab will be administered on the Q14 day schedule. Subsequently Durvalumab will continue as maintenance 1500mg, intravenously (IV) over 60 minutes (+/- 5 minutes), Q28 days up to 1 year or until progression (11 doses), unacceptable toxicity or other reason. If a patient undergoes resection, they will resume durvalumab once appropriately healed from surgery (approximately 4-8 weeks) at discretion of treating medical oncologist.
arm group label: Durvalumab + SABR
other name: Medi 4736
intervention type: Radiation
intervention name: Stereotactic Ablative Body Radiotherapy (SABR)
description: SABR delivered as 6.6 Gy/fraction x 5 fractions given within two weeks will be administered weekdays and will begin D8.
arm group label: Durvalumab + SABR
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eileen O'Reilly, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Durvalumab
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.