<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/NCT03000179</url>
  </required_header>
  <id_info>
    <org_study_id>VICC GI 1679</org_study_id>
    <nct_id>NCT03000179</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Avelumab in Small Intestinal Adenocarcinoma</brief_title>
  <official_title>Pilot Study to Investigate the Safety and Efficacy of Avelumab Monotherapy in Patients With Advanced or Metastatic Adenocarcinoma of the Small Intestine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt-Ingram Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>EMD Serono</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt-Ingram 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 single-agent, open label, one-arm phase 2 pilot study of avelumab in patients with&#xD;
      advanced or metastatic adenocarcinoma of the small intestine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives&#xD;
&#xD;
        -  To describe any antitumor activity of avelumab monotherapy, as measured by the response&#xD;
           rate in patients with advanced or metastatic small intestinal adenocarcinoma.&#xD;
&#xD;
        -  To describe the safety profile of avelumab monotherapy in patients with advanced or&#xD;
           metastatic small intestinal adenocarcinoma.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        -  To determine overall survival, progression-free survival, and duration of response of&#xD;
           avelumab monotherapy in patients with advanced small intestinal adenocarcinoma.&#xD;
&#xD;
        -  To evaluate the association of tumor PD-L1 and PD-1 expression, MSI status, lymphocytic&#xD;
           infiltration, and somatic mutation burden with response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low accrual&#xD;
  </why_stopped>
  <start_date type="Actual">March 3, 2017</start_date>
  <completion_date type="Actual">August 3, 2021</completion_date>
  <primary_completion_date type="Actual">August 3, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate as Measured Using RECIST 1.1</measure>
    <time_frame>Measured every 8 weeks through study completion, an average of 1 year</time_frame>
    <description>Response rate is the proportion of patients with overall complete (CR) or partial response(PR) among patients with valuable response outcome. Overall response will consider both target and non-target lesions, as well as new lesions.&#xD;
Target lesions by CT/MRI: CR: Disappearance of all target lesions. PR: &gt;= 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): &gt;= 20% increase in the sum of diameters of target lesions, In addition, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of new lesions. Non-target lesions: CR: Disappearance of all target lesions. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of applicable tumor marker level above the normal limits. PD: progression of existing non-target lesions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients With Each Worst-Grade Toxicity</measure>
    <time_frame>On-study date to 30 days following final dose of study drug, or until the event is resolved, stabilized, or determined to be irreversible by the participating investigator if beyond 30 days.</time_frame>
    <description>To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Every 3 months after completing treatment up to 5 years</time_frame>
    <description>On study date until death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>On-study date to lesser of date of progression or date of death from any cause measured up to 3 years after treatment</time_frame>
    <description>On-study date until disease progression or death. Progression is &gt;= 20% increase in the sum of diameters of target lesions or non-target lesions, or appearance of new lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Date of first partial or complete response as defined by RECIST 1.1 criteria to date of recurrence or disease progression up to 3 years</time_frame>
    <description>Time from tumor response date to disease progression or death for any reason.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Avelumab Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>Avelumab through a vein once every 2 weeks</description>
    <arm_group_label>Avelumab Monotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed and dated written informed consent.&#xD;
&#xD;
          -  Male or female ≥ 18 years of age.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma of the small intestine that is advanced (not&#xD;
             amenable to surgery) or metastatic (clinical stage IV). For the purposes of this&#xD;
             study, ampullary tumors are considered a part of the duodenum and are classified as&#xD;
             adenocarcinomas of the small intestine.&#xD;
&#xD;
          -  At least one measurable lesion as defined by Response Evaluation Criteria in Solid&#xD;
             Tumors (RECIST) version 1.1 criteria that has not been previously irradiated and which&#xD;
             can be followed by CT or MRI.&#xD;
&#xD;
          -  Adequate organ function including:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 × 109/L&#xD;
&#xD;
               -  Platelets ≥ 100 × 109/L&#xD;
&#xD;
               -  Hemoglobin ≥ 9/g/dL (may have been transfused)&#xD;
&#xD;
               -  Total serum bilirubin ≤ 1.5 times upper limit of normal (ULN)&#xD;
&#xD;
               -  Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤&#xD;
                  2.5 × ULN (or ≤ 5 × ULN if liver metastases are present)&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 30 mL/min as&#xD;
                  calculated using the Cockcroft-Gault (CG) equation&#xD;
&#xD;
          -  Archival tissue [paraffin block(s) or unstained slides from paraffin block(s)] from&#xD;
             the primary tumor and/or a metastatic site judged reasonably available prior to&#xD;
             initiating treatment, or willingness to undergo fresh pre-treatment tumor biopsy.&#xD;
             (Prior to initiating treatment, the screening team must have documentation that an&#xD;
             archival or fresh tumor specimen has been requested from a local or outside facility.&#xD;
             However, physical possession of requested tissue or waiting for histological analysis&#xD;
             or confirmation that an acquired specimen contains tumor tissue sufficient for&#xD;
             analysis is not a requirement prior to initiating treatment.) If no archival tissue is&#xD;
             available and patient consents to a fresh biopsy, but the patient's lesion is deemed&#xD;
             inaccessible to safe biopsy, the patient will be allowed to enroll if otherwise&#xD;
             eligible.&#xD;
&#xD;
          -  Female patients of childbearing potential and male patients able to father children&#xD;
             who have female partners of childbearing potential must agree to use one highly&#xD;
             effective method (defined as less than 1% failure rate per year) and one additional&#xD;
             effective method of contraception (Appendix 4) from 15 days prior to first trial&#xD;
             treatment administration until at least 60 days after study participant's final dose&#xD;
             of avelumab.&#xD;
&#xD;
               -  Females of childbearing potential are defined as those who are not surgically&#xD;
                  sterile or post-menopausal (i.e. patient has not had a bilateral tubal ligation,&#xD;
                  a bilateral oophorectomy, or a complete hysterectomy; or has not been amenorrheic&#xD;
                  for 12 months without an alternative medical cause). Post-menopausal status in&#xD;
                  females under 55 years of age should be confirmed with a serum&#xD;
                  follicle-stimulating hormone (FSH) level within laboratory reference range for&#xD;
                  postmenopausal women.&#xD;
&#xD;
               -  Male patients able to father children are defined as those who are not surgically&#xD;
                  sterile (i.e. patient has not had a vasectomy).&#xD;
&#xD;
          -  Serum pregnancy test (for females of childbearing potential) negative at screening.&#xD;
&#xD;
          -  Re-enrollment of a subject that has discontinued the study as a pre-treatment screen&#xD;
             failure (i.e. a consented patient who did not receive avelumab) is permitted. If&#xD;
             re-enrolled, the subject must be re-consented. Only the screening procedures performed&#xD;
             outside of protocol-specified timing must be repeated.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  There is no restriction on the number of prior therapies. However, prior therapy with&#xD;
             antibody or drug specifically targeting T cell regulatory proteins, including but not&#xD;
             limited to the following is not allowed: Prior immunotherapy with IL-2 or IFN-α, or an&#xD;
             anti-PD-1 (including nivolumab), anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic&#xD;
             T-lymphocyteassociated antigen-4 (CTLA-4) antibody (including ipilimumab), or any&#xD;
             other antibody or drug specifically targeting T-cell co-stimulation or checkpoint&#xD;
             pathways.&#xD;
&#xD;
          -  Within 28 days before first dose of avelumab: Anti-cancer treatment, major surgery&#xD;
             requiring general anesthesia, or the use of any investigational agent.&#xD;
&#xD;
          -  Within 14 days before first dose of avelumab: Therapeutic or palliative radiation&#xD;
             therapy. (Subjects receiving bisphosphonate or denosumab are eligible provided&#xD;
             treatment was initiated at least 14 days before the first dose of avelumab.)&#xD;
&#xD;
          -  Current use of immunosuppressive medication, except the following:&#xD;
&#xD;
               -  Subjects are permitted the use of corticosteroids with minimal systemic&#xD;
                  absorption (e.g. topical, ocular, intra-articular, intranasal, and inhaled);&#xD;
&#xD;
               -  Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or&#xD;
                  equivalent are permitted;&#xD;
&#xD;
               -  A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. CT&#xD;
                  scan premedication against contrast dye allergy) or for treatment of&#xD;
                  non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by&#xD;
                  a contact allergen) is permitted.&#xD;
&#xD;
          -  Previous malignant disease other than adenocarcinoma of the small intestine within the&#xD;
             last 5 years, with the exception of basal or squamous cell carcinoma of the skin or&#xD;
             cervical carcinoma in situ considered curatively treated (i.e. complete remission&#xD;
             achieved at least 2 years prior to first dose of avelumab AND additional therapy not&#xD;
             required while receiving study treatment).&#xD;
&#xD;
          -  All subjects with brain metastases, expect those meeting the following criteria:&#xD;
&#xD;
               -  Brain metastases that have been treated locally and are clinically stable for at&#xD;
                  least 2 weeks prior to enrollment&#xD;
&#xD;
               -  No ongoing neurological symptoms that are related to the brain localization of&#xD;
                  the disease (sequelae that are a consequence of the treatment of the brain&#xD;
                  metastases are acceptable.&#xD;
&#xD;
               -  Subjects must be either off steroids or on a stable or decreasing dose of ≤ 10 mg&#xD;
                  daily prednisone (or equivalent)&#xD;
&#xD;
          -  Receipt of any organ transplantation including allogeneic stem-cell transplantation.&#xD;
&#xD;
          -  Significant acute or chronic infections requiring systemic therapy.&#xD;
&#xD;
               -  Known history of testing positive for human immunodeficiency virus (HIV), or&#xD;
                  acquired immunodeficiency syndrome (AIDS).&#xD;
&#xD;
               -  Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening&#xD;
                  (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test&#xD;
                  positive).&#xD;
&#xD;
          -  Active autoimmune disease with reasonable possibility of clinically significant&#xD;
             deterioration when receiving an immunostimulatory agent:&#xD;
&#xD;
               -  Subjects with Type 1 diabetes mellitus, vitiligo, psoriasis, hypo- or&#xD;
                  hyperthyroid disease not requiring immunosuppressive treatment are eligible.&#xD;
&#xD;
          -  Interstitial lung disease that is symptomatic or which may interfere with the&#xD;
             detection or management of suspected drug-related pulmonary toxicity.&#xD;
&#xD;
          -  Uncontrolled asthma [defined as having 3 or more of the following features of&#xD;
             partially controlled asthma within 28 days prior to starting study treatment: Daytime&#xD;
             symptoms more than twice per week, any limitation of activities, any nocturnal&#xD;
             symptoms/awaking, need for reliever/rescue inhaler more than twice per week, or known&#xD;
             lung function (PEF or FEV1) without administration of a bronchodilator that is &lt; 80%&#xD;
             predicted or personal best (if known)].&#xD;
&#xD;
          -  Current symptomatic congestive heart failure (New York Heart Association &gt; class II),&#xD;
             unstable cardiac arrhythmia requiring therapy (e.g. medication or pacemaker), unstable&#xD;
             angina (e.g. new, worsening or persistent chest discomfort), or uncontrolled&#xD;
             hypertension (systolic &gt; 160 mmHg or diastolic &gt; 100mmHg). Or any of the following&#xD;
             occurring within 6 months (180 days) prior to first dose of avelumab: Myocardial&#xD;
             infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or&#xD;
             transient ischemic attack, or serious cardiac arrhythmia requiring medication. (Use of&#xD;
             antihypertensive medication to control blood pressure is allowed.)&#xD;
&#xD;
          -  Concurrent treatment with a non-permitted drug.&#xD;
&#xD;
          -  Requirement of anticoagulant therapy with oral vitamin K antagonists such as Coumadin&#xD;
             (warfarin). Low-dose anticoagulants for the maintenance of patency in a central venous&#xD;
             access device or the prevention of deep vein thrombosis or pulmonary embolism is&#xD;
             allowed. Therapeutic use of low molecular weight heparin is allowed.&#xD;
&#xD;
          -  Persisting toxicity related to prior therapy that has not reduced to Grade 1 [National&#xD;
             Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03;&#xD;
             however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable.&#xD;
&#xD;
          -  Known severe (Grade ≥ 3 NCI-CTCAE v4.03) hypersensitivity reactions to monoclonal&#xD;
             antibodies, including hypersensitivity to the investigational agent or any component&#xD;
             in its formulations, or history of anaphylaxis.&#xD;
&#xD;
          -  Vaccination within 28 days of the first dose of avelumab and while on trial is&#xD;
             prohibited, except for administration of inactivated vaccines (for example,&#xD;
             inactivated influenza vaccine).&#xD;
&#xD;
          -  Pregnant or breastfeeding females.&#xD;
&#xD;
          -  Known alcohol or drug abuse.&#xD;
&#xD;
          -  Prisoners or subjects who are involuntarily incarcerated.&#xD;
&#xD;
          -  Other severe acute or chronic medical condition, including colitis, inflammatory bowl&#xD;
             disease, pneumonitis, pulmonary fibrosis, or psychiatric condition including recent&#xD;
             (within the past year) or active suicidal ideation or behavior; or laboratory&#xD;
             abnormalities that may increase the risk associated with study participation or study&#xD;
             treatment administration or may interfere with the interpretation of study results&#xD;
             and, in the judgment of the investigator, would make the patient inappropriate for&#xD;
             entry into this study.&#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>Dana Cardin, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt-Ingram Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt-Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <results_first_submitted>February 18, 2022</results_first_submitted>
  <results_first_submitted_qc>March 22, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 14, 2022</results_first_posted>
  <last_update_submitted>March 22, 2022</last_update_submitted>
  <last_update_submitted_qc>March 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt-Ingram Cancer Center</investigator_affiliation>
    <investigator_full_name>Dana Cardin, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>small bowel cancer, small bowel carcinoma</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>Avelumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT03000179/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled onto this study at Vanderbilt University Medical Center in Nashville, TN from March 2017 to August 2019. The study closed early due to low accrual.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Avelumab Monotherapy</title>
          <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Avelumab Monotherapy</title>
          <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate as Measured Using RECIST 1.1</title>
        <description>Response rate is the proportion of patients with overall complete (CR) or partial response(PR) among patients with valuable response outcome. Overall response will consider both target and non-target lesions, as well as new lesions.&#xD;
Target lesions by CT/MRI: CR: Disappearance of all target lesions. PR: &gt;= 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): &gt;= 20% increase in the sum of diameters of target lesions, In addition, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of new lesions. Non-target lesions: CR: Disappearance of all target lesions. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of applicable tumor marker level above the normal limits. PD: progression of existing non-target lesions.</description>
        <time_frame>Measured every 8 weeks through study completion, an average of 1 year</time_frame>
        <population>Patients with advanced small intestinal adenocarcinoma or ampullary tumors, efficacy-evaluable.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab Monotherapy</title>
            <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate as Measured Using RECIST 1.1</title>
          <description>Response rate is the proportion of patients with overall complete (CR) or partial response(PR) among patients with valuable response outcome. Overall response will consider both target and non-target lesions, as well as new lesions.&#xD;
Target lesions by CT/MRI: CR: Disappearance of all target lesions. PR: &gt;= 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): &gt;= 20% increase in the sum of diameters of target lesions, In addition, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of new lesions. Non-target lesions: CR: Disappearance of all target lesions. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of applicable tumor marker level above the normal limits. PD: progression of existing non-target lesions.</description>
          <population>Patients with advanced small intestinal adenocarcinoma or ampullary tumors, efficacy-evaluable.</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.29" lower_limit="0.08" upper_limit="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Each Worst-Grade Toxicity</title>
        <description>To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma</description>
        <time_frame>On-study date to 30 days following final dose of study drug, or until the event is resolved, stabilized, or determined to be irreversible by the participating investigator if beyond 30 days.</time_frame>
        <population>all participants</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab Monotherapy</title>
            <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Each Worst-Grade Toxicity</title>
          <description>To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma</description>
          <population>all participants</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anemia, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue, Grade2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infusion related reaction. Grade2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine aminotransferase increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline phosphatase increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anorexia, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood bilirubin increased, Grade1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diarrhea, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diabetic ketoacidosis, Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Back pain, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Diverticulitis per upper GI series, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypokalemia, Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatremia, Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash maculo-papular, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urticaria, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>On study date until death from any cause</description>
        <time_frame>Every 3 months after completing treatment up to 5 years</time_frame>
        <population>all participants</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab Monotherapy</title>
            <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>On study date until death from any cause</description>
          <population>all participants</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" lower_limit="3.8" upper_limit="NA">Insufficient number of patients with the death event</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival</title>
        <description>On-study date until disease progression or death. Progression is &gt;= 20% increase in the sum of diameters of target lesions or non-target lesions, or appearance of new lesions.</description>
        <time_frame>On-study date to lesser of date of progression or date of death from any cause measured up to 3 years after treatment</time_frame>
        <population>all participants</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab Monotherapy</title>
            <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival</title>
          <description>On-study date until disease progression or death. Progression is &gt;= 20% increase in the sum of diameters of target lesions or non-target lesions, or appearance of new lesions.</description>
          <population>all participants</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" lower_limit="3.0" upper_limit="NA">Insufficient number of patients with progression.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Time from tumor response date to disease progression or death for any reason.</description>
        <time_frame>Date of first partial or complete response as defined by RECIST 1.1 criteria to date of recurrence or disease progression up to 3 years</time_frame>
        <population>Patients who had partial response.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab Monotherapy</title>
            <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Time from tumor response date to disease progression or death for any reason.</description>
          <population>Patients who had partial response.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.9" lower_limit="3.0" upper_limit="18.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From study entry to up to 28 days from the last dose of avelumab up to approximately 1 year.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Avelumab Monotherapy</title>
          <description>Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.&#xD;
Avelumab: Avelumab through a vein once every 2 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic Ketoacidos</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Colonic obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteremia bloodstream infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="20" subjects_affected="7" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Gastrointestinal fistula</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Small intestinal mucositis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Limb edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Facial pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Small intestine infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>INR increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Generalized muscle weaknes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Extremity pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>memory impairement</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Psychosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Couph</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Photosensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Teresa Melton</name_or_title>
      <organization>Vanderbilt-Ingram Cancer Center</organization>
      <phone>615-936-7423</phone>
      <email>teresa.melton@vumc.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03000179
org study id: VICC GI 1679
nct id: NCT03000179
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single-agent, open label, one-arm phase 2 pilot study of avelumab in patients with
      advanced or metastatic adenocarcinoma of the small intestine.
Primary Objectives

        -  To describe any antitumor activity of avelumab monotherapy, as measured by the response
           rate in patients with advanced or metastatic small intestinal adenocarcinoma.

        -  To describe the safety profile of avelumab monotherapy in patients with advanced or
           metastatic small intestinal adenocarcinoma.

      Secondary Objectives

        -  To determine overall survival, progression-free survival, and duration of response of
           avelumab monotherapy in patients with advanced small intestinal adenocarcinoma.

        -  To evaluate the association of tumor PD-L1 and PD-1 expression, MSI status, lymphocytic
           infiltration, and somatic mutation burden with response.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate as Measured Using RECIST 1.1
time frame: Measured every 8 weeks through study completion, an average of 1 year
description: Response rate is the proportion of patients with overall complete (CR) or partial response(PR) among patients with valuable response outcome. Overall response will consider both target and non-target lesions, as well as new lesions.
Target lesions by CT/MRI: CR: Disappearance of all target lesions. PR: >= 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): >= 20% increase in the sum of diameters of target lesions, In addition, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of new lesions. Non-target lesions: CR: Disappearance of all target lesions. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of applicable tumor marker level above the normal limits. PD: progression of existing non-target lesions.
measure: Number of Patients With Each Worst-Grade Toxicity
time frame: On-study date to 30 days following final dose of study drug, or until the event is resolved, stabilized, or determined to be irreversible by the participating investigator if beyond 30 days.
description: To describe the safety profile of avelumab monotherapy in patients with advanced or metastatic small intestinal adenocarcinoma
measure: Overall Survival
time frame: Every 3 months after completing treatment up to 5 years
description: On study date until death from any cause
measure: Progression Free Survival
time frame: On-study date to lesser of date of progression or date of death from any cause measured up to 3 years after treatment
description: On-study date until disease progression or death. Progression is >= 20% increase in the sum of diameters of target lesions or non-target lesions, or appearance of new lesions.
measure: Duration of Response
time frame: Date of first partial or complete response as defined by RECIST 1.1 criteria to date of recurrence or disease progression up to 3 years
description: Time from tumor response date to disease progression or death for any reason.
arm group label: Avelumab Monotherapy
arm group type: Experimental
description: Participants receive avelumab by IV infusion following pretreatment with H1 blockers and acetaminophen once every 2 weeks.
intervention type: Drug
intervention name: Avelumab
description: Avelumab through a vein once every 2 weeks
arm group label: Avelumab Monotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dana Cardin, M.D.
role: Principal Investigator
affiliation: Vanderbilt-Ingram Cancer Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt-Ingram Cancer Center
investigator full name: Dana Cardin, MD
investigator title: Principal Investigator
mesh term: Adenocarcinoma
mesh term: Avelumab
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 