<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/NCT03006848</url>
  </required_header>
  <id_info>
    <org_study_id>OSTPDL1</org_study_id>
    <secondary_id>Pfizer W1211733 (OSTPDL1)</secondary_id>
    <secondary_id>Gateway RESAG</secondary_id>
    <nct_id>NCT03006848</nct_id>
  </id_info>
  <brief_title>A Phase II Trial of Avelumab in Patients With Recurrent or Progressive Osteosarcoma</brief_title>
  <official_title>A Phase II Trial of Avelumab, A Fully Human Antibody That Targets Cells Expressing PD-L1, in Patients With Recurrent or Progressive Osteosarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gateway for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Jude Children's Research Hospital</source>
  <oversight_info>
    <has_dmc>No</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 clinical trial seeks to determine if avelumab will be effective in facilitating removal&#xD;
      of all gross tumor in the event of a relapse of osteosarcoma in pediatric patients. Avelumab&#xD;
      will be evaluated using dosing that has previously been determined in adult studies.&#xD;
&#xD;
      Primary Objectives:&#xD;
&#xD;
        -  To estimate the response rate to 4 cycles of avelumab in patients with recurrent or&#xD;
           progressive osteosarcoma.&#xD;
&#xD;
        -  To estimate the 16-week progression free survival of patients with recurrent or&#xD;
           progressive osteosarcoma after treatment with avelumab.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        -  To describe the toxicities associated with the administration of avelumab in patients&#xD;
           with recurrent or progressive osteosarcoma.&#xD;
&#xD;
        -  To assess the quality of life of patients with recurrent or progressive osteosarcoma&#xD;
           undergoing treatment with avelumab, and to explore relationships between clinical&#xD;
           factors and patient-reported health-related quality of life (HRQOL) outcomes.&#xD;
&#xD;
      Exploratory Objectives:&#xD;
&#xD;
        -  To explore factors associated with response in patients treated with avelumab after&#xD;
           recurrent or progressive osteosarcoma (e.g. tumor PD-L1 expression).&#xD;
&#xD;
        -  To measure parameters of immune activation including subsets of peripheral blood&#xD;
           mononuclear cells (PBMCs) and serum markers of immune activation.&#xD;
&#xD;
        -  To evaluate the role of T-cells in immune checkpoint blockade via measures of cell&#xD;
           proliferation, co-inhibitory receptor expression on CD8 T cells, T cell repertoire, and&#xD;
           epigenetic programming.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2 study using a traditional Simon two-stage design. Patients 12 years or&#xD;
      greater with recurrent/refractory osteosarcoma will be administered avelumab at a dose of 10&#xD;
      mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting&#xD;
      28 days.&#xD;
&#xD;
      Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26&#xD;
      cycles. Progression free survival and response to therapy after 4 cycles of treatment will be&#xD;
      assessed. In addition, the toxicity profile of avelumab in this population will be closely&#xD;
      monitored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 16, 2017</start_date>
  <completion_date type="Actual">March 18, 2020</completion_date>
  <primary_completion_date type="Actual">March 18, 2020</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>Response Rate</measure>
    <time_frame>At the end of 4 cycles of avelumab (approximately 4 months)</time_frame>
    <description>The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>At the end of 4 cycles of avelumab (approximately 4 months)</time_frame>
    <description>The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Target Toxicities</measure>
    <time_frame>At the end of treatment (up to 2 years after enrollment of last participant)</time_frame>
    <description>Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Factors Associated With Response</measure>
    <time_frame>Following completion of therapy for last participant (up to 2 years after enrollment)</time_frame>
    <description>Logistic regression analysis will be conducted to explore factors which may associate with response.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Parameters of Immune Activation</measure>
    <time_frame>Baseline prior to start of therapy and following 2 cycles of therapy (up to 8 weeks after last enrollment)</time_frame>
    <description>Descriptive statistics will be provided.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Cell Proliferation</measure>
    <time_frame>Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).</time_frame>
    <description>Descriptive statistics will be provided.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Co-inhibitory Receptor Expression on CD8 T Cells</measure>
    <time_frame>Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).</time_frame>
    <description>Descriptive statistics will be provided.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Quality of Life</measure>
    <time_frame>From baseline prior to start of treatment through the end of avelumab therapy (up to approximately 2 years)</time_frame>
    <description>Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Osteosarcoma</condition>
  <arm_group>
    <arm_group_label>Avelumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants with recurrent/refractory osteosarcoma who consent to the study.&#xD;
Interventions: Avelumab and quality of life questionnaires.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.</description>
    <arm_group_label>Avelumab</arm_group_label>
    <other_name>MSB0010718C</other_name>
    <other_name>anti-PD-L1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <description>To assess quality of life, patients will complete questionnaires at four time points.</description>
    <arm_group_label>Avelumab</arm_group_label>
    <other_name>PROMIS Pediatric Profile</other_name>
    <other_name>PROMIS Adult Profile</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be &gt; 12 years of age but &lt; 50 years of age at the time of enrollment.&#xD;
&#xD;
          -  Patients must have histologic verification of osteosarcoma at initial diagnosis or&#xD;
             relapse.&#xD;
&#xD;
          -  Patients must have had evidence of having relapsed, progressed or become refractory to&#xD;
             conventional therapy.&#xD;
&#xD;
          -  Patients must have measurable disease, documented by clinical, radiographic or&#xD;
             histologic criteria. Disease must be bi-dimensionally measurable by computed&#xD;
             tomography (CT) or magnetic resonance imaging (MRI).&#xD;
&#xD;
          -  Patients must have a performance status of ≥ 50 using the Karnofsky scale for patients&#xD;
             &gt; 16 years of age and the Lansky scale for patients ≤ 16 years of age.&#xD;
&#xD;
          -  Patients must have a life expectancy of ≥ 6 weeks.&#xD;
&#xD;
          -  Patients must have fully recovered from the acute toxic effects of all prior&#xD;
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study.&#xD;
&#xD;
               1. Myelosuppressive chemotherapy: must not have received within 3 weeks of entry&#xD;
                  onto this study.&#xD;
&#xD;
               2. Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy&#xD;
                  with a biologic agent.&#xD;
&#xD;
               3. Immunotherapies: at least 42 days must have elapsed since a prior therapy that&#xD;
                  included a monoclonal antibody or any other type of immunotherapy (e.g. chimeric&#xD;
                  antigen receptor (CAR) T cell therapy).&#xD;
&#xD;
               4. Radiation therapy (RT): ≥ 2 weeks for local palliative RT (small port); ≥ 6&#xD;
                  months must have elapsed if prior craniospinal RT or if ≥ 50% radiation of the&#xD;
                  pelvis; ≥ 6 weeks must have elapsed if other substantial bone marrow (BM)&#xD;
                  radiation.&#xD;
&#xD;
          -  Organ Function Requirements:&#xD;
&#xD;
               1. Adequate bone marrow function defined as:&#xD;
&#xD;
                    -  Peripheral absolute neutrophil count (ANC) ≥ 1500/mm3&#xD;
&#xD;
                    -  Platelet count ≥ 100,000/mm3 (transfusion independent)&#xD;
&#xD;
                    -  Hemoglobin ≥ 9.0 g/dL (may receive RBC transfusions)&#xD;
&#xD;
               2. Adequate renal function defined as:&#xD;
&#xD;
                    -  Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73m2 OR&#xD;
&#xD;
                    -  Serum creatinine based on age/gender as follows: (threshold creatinine&#xD;
                       values were derived from the Schwartz formula for estimating GFR).&#xD;
&#xD;
                         -  Age is: 12 to &lt;13 years, then maximum creatinine is 1.2 mg/DL for male&#xD;
                            and female.&#xD;
&#xD;
                         -  Age is: 13 to &lt;16 years, then maximum creatinine is 1.5 mg/DL for male&#xD;
                            and 1.4 mg/DL for female.&#xD;
&#xD;
                         -  Age is: ≥16 years, then maximum creatinine is 1.7 mg/DL for male and&#xD;
                            1.4 mg/DL for female.&#xD;
&#xD;
               3. Adequate liver function defined as:&#xD;
&#xD;
                    -  Total Bilirubin ≤ 1.5x the institutional upper limit of normal (IULN) for&#xD;
                       age&#xD;
&#xD;
                    -  ALT (SGPT) and AST (SGOT) &lt; 2.5 x IULN for age (or &lt; 5 x IULN for patients&#xD;
                       with documented metastatic disease to the liver)&#xD;
&#xD;
                    -  Serum albumin &gt; 2 g/dL&#xD;
&#xD;
               4. Serum lipase ≤ upper limit of normal (IULN).&#xD;
&#xD;
               5. Patients must have documented pulse oximetry ≥ 92% on room air.&#xD;
&#xD;
          -  Female patients of childbearing potential must have a negative serum or urine&#xD;
             pregnancy test within 7 days of enrollment.&#xD;
&#xD;
          -  Male or female patients who are sexually active and of reproductive potential must&#xD;
             agree to use an effective contraceptive method throughout the study and for at least&#xD;
             60 days after last avelumab treatment administration. Abstinence is an acceptable form&#xD;
             of contraception.&#xD;
&#xD;
          -  Patients must not currently be using other investigational agents.&#xD;
&#xD;
          -  Patients must not currently be using other anti-cancer agent.&#xD;
&#xD;
          -  Patients must be able to comply with the safety monitoring of the study in the opinion&#xD;
             of the investigator.&#xD;
&#xD;
          -  Written, informed consent and assent following Institutional Review Board, NCI, FDA&#xD;
             and OHRP guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Central nervous system (CNS) metastases.&#xD;
&#xD;
          -  Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal,&#xD;
             inhaled, topical steroids, or local steroid injection (e.g., intra-articular&#xD;
             injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone&#xD;
             or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT&#xD;
             scan premedication).&#xD;
&#xD;
          -  Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory&#xD;
             agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid&#xD;
             diseases not requiring immunosuppressive treatment are eligible.&#xD;
&#xD;
          -  Active infection requiring systemic therapy.&#xD;
&#xD;
          -  Known history of testing positive for HIV or known acquired immunodeficiency syndrome.&#xD;
&#xD;
          -  Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive&#xD;
             HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).&#xD;
&#xD;
          -  Patient who has received vaccination within 4 weeks of the first dose of avelumab and&#xD;
             while on trials is prohibited except for administration of inactivated vaccines.&#xD;
&#xD;
          -  Known prior severe hypersensitivity to investigational product or any component in its&#xD;
             formulations, including known severe hypersensitivity reactions to monoclonal&#xD;
             antibodies (NCI CTCAE v4.03 Grade ≥ 3).&#xD;
&#xD;
          -  Clinically significant (i.e., active) cardiovascular disease: cerebral vascular&#xD;
             accident/stroke (&lt; 6 months prior to enrollment), myocardial infarction (&lt; 6 months&#xD;
             prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart&#xD;
             Association Classification Class II, see Appendix II), or serious cardiac arrhythmia&#xD;
             requiring medication.&#xD;
&#xD;
          -  Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade &gt; 1); however,&#xD;
             alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety&#xD;
             risk based on investigator's judgment are acceptable&#xD;
&#xD;
          -  Other severe acute or chronic medical conditions including colitis, inflammatory bowel&#xD;
             disease, pneumonitis, pulmonary fibrosis or psychiatric conditions 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;
&#xD;
          -  Patients with active diarrhea &gt; CTCAE v4.03 Grade 2.&#xD;
&#xD;
          -  Patients who have previously received a prior organ transplantation, including&#xD;
             allogeneic stem cell transplantation.&#xD;
&#xD;
          -  Female patients who are pregnant or actively breastfeeding.&#xD;
&#xD;
          -  Patients who have previously received anti-PD1 or anti-PD-L1 therapy. Patients who&#xD;
             have previously received anti-CTLA-4 therapy (e.g. ipilimumab) are eligible for study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael W. Bishop, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude Children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org/protocols</url>
    <description>Clinical Trials Open at St. Jude</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <results_first_submitted>July 21, 2021</results_first_submitted>
  <results_first_submitted_qc>August 19, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 16, 2021</results_first_posted>
  <disposition_first_submitted>March 4, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>August 19, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 16, 2021</disposition_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Osteosarcoma</keyword>
  <keyword>PD-L1</keyword>
  <keyword>Immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteosarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</mesh_term>
  </intervention_browse>
  <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>June 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT03006848/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 19 patients were enrolled on the study from February 2017 to April 2021</recruitment_details>
      <pre_assignment_details>18 out of 19 enrolled patients received treatment. The patient who did not receive treatment was found to be ineligible and thus was a screen failure.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Avelumab</title>
          <description>All participants with recurrent/refractory osteosarcoma who consent to the study.&#xD;
Interventions: Avelumab and quality of life questionnaires.&#xD;
Avelumab: Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.&#xD;
Questionnaires: To assess quality of life, patients will complete questionnaires at four time points.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Avelumab</title>
          <description>All participants with recurrent/refractory osteosarcoma who consent to the study.&#xD;
Interventions: Avelumab and quality of life questionnaires.&#xD;
Avelumab: Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.&#xD;
Questionnaires: To assess quality of life, patients will complete questionnaires at four time points.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>years</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.0" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Declined Respond</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <title>St. Jude Children's Research Hospital</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Memorial Sloan-Kettering Cancer Center</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Children's Hospital of Los Angeles</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Texas Children's Research Hospital</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Status at time of enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Progressive Disease</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Recurrent Disease</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Response Rate</title>
        <description>The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.</description>
        <time_frame>At the end of 4 cycles of avelumab (approximately 4 months)</time_frame>
        <population>RECIST response [complete response + partial response (CR+PR)]</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab</title>
            <description>All participants with recurrent/refractory osteosarcoma who consent to the study.&#xD;
Interventions: Avelumab and quality of life questionnaires.&#xD;
Avelumab: Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.&#xD;
Questionnaires: To assess quality of life, patients will complete questionnaires at four time points.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate</title>
          <description>The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.</description>
          <population>RECIST response [complete response + partial response (CR+PR)]</population>
          <units>percentage 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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival</title>
        <description>The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.</description>
        <time_frame>At the end of 4 cycles of avelumab (approximately 4 months)</time_frame>
        <population>Of the 18 eligible patients who received treatment, 17 patients had disease progression while on study and one patient died off study.</population>
        <group_list>
          <group group_id="O1">
            <title>Progression-free Survival</title>
            <description>The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.</description>
          <population>Of the 18 eligible patients who received treatment, 17 patients had disease progression while on study and one patient died off study.</population>
          <units>percentage of weeks</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="6.7" upper_limit="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Target Toxicities</title>
        <description>Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).</description>
        <time_frame>At the end of treatment (up to 2 years after enrollment of last participant)</time_frame>
        <population>[Not Specified]</population>
        <group_list>
          <group group_id="O1">
            <title>Target Toxicities</title>
            <description>Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).</description>
          </group>
        </group_list>
        <measure>
          <title>Target Toxicities</title>
          <description>Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).</description>
          <population>[Not Specified]</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Dyspnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infection and infestations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood and lymphatic system disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cardiac disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Investigations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Factors Associated With Response</title>
        <description>Logistic regression analysis will be conducted to explore factors which may associate with response.</description>
        <time_frame>Following completion of therapy for last participant (up to 2 years after enrollment)</time_frame>
        <population>[Not Specified]</population>
        <group_list>
          <group group_id="O1">
            <title>Factors Associated With Response</title>
            <description>Logistic regression analysis will be conducted to explore factors which may associate with response.</description>
          </group>
        </group_list>
        <measure>
          <title>Factors Associated With Response</title>
          <description>Logistic regression analysis will be conducted to explore factors which may associate with response.</description>
          <population>[Not Specified]</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Parameters of Immune Activation</title>
        <description>Descriptive statistics will be provided.</description>
        <time_frame>Baseline prior to start of therapy and following 2 cycles of therapy (up to 8 weeks after last enrollment)</time_frame>
        <population>[Not Specified]</population>
        <group_list>
          <group group_id="O1">
            <title>Change in Parameters of Immune Activation</title>
            <description>Descriptive statistics will be provided.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Parameters of Immune Activation</title>
          <description>Descriptive statistics will be provided.</description>
          <population>[Not Specified]</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Cell Proliferation</title>
        <description>Descriptive statistics will be provided.</description>
        <time_frame>Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).</time_frame>
        <population>[Not Specified]</population>
        <group_list>
          <group group_id="O1">
            <title>Change in Cell Proliferation</title>
            <description>Descriptive statistics will be provided.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Cell Proliferation</title>
          <description>Descriptive statistics will be provided.</description>
          <population>[Not Specified]</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Co-inhibitory Receptor Expression on CD8 T Cells</title>
        <description>Descriptive statistics will be provided.</description>
        <time_frame>Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).</time_frame>
        <population>[Not Specified]</population>
        <group_list>
          <group group_id="O1">
            <title>Change in Co-inhibitory Receptor Expression on CD8 T Cells</title>
            <description>Descriptive statistics will be provided.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Co-inhibitory Receptor Expression on CD8 T Cells</title>
          <description>Descriptive statistics will be provided.</description>
          <population>[Not Specified]</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Quality of Life</title>
        <description>Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.</description>
        <time_frame>From baseline prior to start of treatment through the end of avelumab therapy (up to approximately 2 years)</time_frame>
        <population>[Not Specified]</population>
        <group_list>
          <group group_id="O1">
            <title>Change in Quality of Life</title>
            <description>Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quality of Life</title>
          <description>Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.</description>
          <population>[Not Specified]</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Acute adverse events were collected from study enrollment up to 4 weeks after completion of chemotherapy/radiation therapy, whichever came last. Long term toxicity was captured at every visit up to 3 years from study enrollment.</time_frame>
      <desc>[Not specified]</desc>
      <group_list>
        <group group_id="E1">
          <title>Avelumab</title>
          <description>[Not specified]</description>
        </group>
      </group_list>
      <serious_events>
        <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="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders</sub_title>
                <description>Pericardial effusion</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Abdominal pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Aspartate aminotransferase increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Alanine aminotransferase increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <description>Hyponatremia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified</sub_title>
                <description>Neoplasms benign, malignant and unspecified</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <description>Stroke</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Dyspnea</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Bronchopulmonary hemorrhage</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <description>Lung infection</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic system disorders</sub_title>
                <description>Thromboembolic event</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="15" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic system disorders</sub_title>
                <description>Anemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorders</sub_title>
                <description>Blood and lymphatic system disorders - Other</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders</sub_title>
                <description>Sinus tachycardia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cardiac disorders</sub_title>
                <description>Pericardial tamponade</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Endocrine disorders</sub_title>
                <description>Hyperthyroidism</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Diarrhea</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Gastritis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Constipation</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Nausea</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Abdominal pain</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Hemorrhoids</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Rectal pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Fever</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Pain</description>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Fatigue</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Non-cardiac chest pain</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions</sub_title>
                <description>Gait disturbance</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Immune system disorders</sub_title>
                <description>Autoimmune disorder</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <description>Lung infection</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <description>Urinary tract infection</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, poisoning and procedural complications</sub_title>
                <description>Fall</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Alkaline phosphatase increased</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Aspartate aminotransferase increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Alanine aminotransferase increased</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Investigations</sub_title>
                <description>Blood bilirubin increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <description>Hyperglycemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <description>Hypokalemia</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <description>Hyponatremia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorders</sub_title>
                <description>Back pain</description>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <description>Paresthesia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <description>Peripheral sensory neuropathy</description>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <description>Headache</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal and urinary disorders</sub_title>
                <description>Proteinuria</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Dyspnea</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Pleuritic pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Allergic rhinitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Pneumonitis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Bronchopulmonary hemorrhage</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders</sub_title>
                <description>Cough</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders</sub_title>
                <description>Rash acneiform</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders</sub_title>
                <description>Alopecia</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="18"/>
              </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>
    <limitations_and_caveats>One patient changed administration schedule for C2D15 in cycle 2 due to family vacation plan. The variance in dates was submitted to IRB and the patient was approved to continue on treatment when returns from the trip.&#xD;
One patient was unable to travel from Puerto Rico due to hurricane devastation. Dose C2D15 skipped in cycle 2.&#xD;
Medications were given one or two day(s) earlier or later than the scheduled date for a few patients.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Michael Bishop</name_or_title>
      <organization>St Jude Children's Research Hospital</organization>
      <phone>866-278-5833</phone>
      <email>referralinfo@stjude.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/NCT03006848
org study id: OSTPDL1
secondary id: Pfizer W1211733 (OSTPDL1)
secondary id: Gateway RESAG
nct id: NCT03006848
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This clinical trial seeks to determine if avelumab will be effective in facilitating removal
      of all gross tumor in the event of a relapse of osteosarcoma in pediatric patients. Avelumab
      will be evaluated using dosing that has previously been determined in adult studies.

      Primary Objectives:

        -  To estimate the response rate to 4 cycles of avelumab in patients with recurrent or
           progressive osteosarcoma.

        -  To estimate the 16-week progression free survival of patients with recurrent or
           progressive osteosarcoma after treatment with avelumab.

      Secondary Objective:

        -  To describe the toxicities associated with the administration of avelumab in patients
           with recurrent or progressive osteosarcoma.

        -  To assess the quality of life of patients with recurrent or progressive osteosarcoma
           undergoing treatment with avelumab, and to explore relationships between clinical
           factors and patient-reported health-related quality of life (HRQOL) outcomes.

      Exploratory Objectives:

        -  To explore factors associated with response in patients treated with avelumab after
           recurrent or progressive osteosarcoma (e.g. tumor PD-L1 expression).

        -  To measure parameters of immune activation including subsets of peripheral blood
           mononuclear cells (PBMCs) and serum markers of immune activation.

        -  To evaluate the role of T-cells in immune checkpoint blockade via measures of cell
           proliferation, co-inhibitory receptor expression on CD8 T cells, T cell repertoire, and
           epigenetic programming.
This is a Phase 2 study using a traditional Simon two-stage design. Patients 12 years or
      greater with recurrent/refractory osteosarcoma will be administered avelumab at a dose of 10
      mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting
      28 days.

      Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26
      cycles. Progression free survival and response to therapy after 4 cycles of treatment will be
      assessed. In addition, the toxicity profile of avelumab in this population will be closely
      monitored.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate
time frame: At the end of 4 cycles of avelumab (approximately 4 months)
description: The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.
measure: Progression-free Survival
time frame: At the end of 4 cycles of avelumab (approximately 4 months)
description: The study is designed by treating RECIST response [complete response + partial response (CR+PR)] after 4-cycle treatment of avelumab and the 16-week progression-free survival (PFS) as dual binary endpoints. Patients who fail to be evaluated at the end of the 4-cycle will be counted as failure.
measure: Target Toxicities
time frame: At the end of treatment (up to 2 years after enrollment of last participant)
description: Target toxicities for avelumab treatment are defined as any grade 3-5 dyspnea, infusion-related reactions, or immune related adverse events at least possibly attributable to the agent observed anytime during the 26-cycle treatment period that a patient is on study (including the period between off treatment and off study).
measure: Factors Associated With Response
time frame: Following completion of therapy for last participant (up to 2 years after enrollment)
description: Logistic regression analysis will be conducted to explore factors which may associate with response.
measure: Change in Parameters of Immune Activation
time frame: Baseline prior to start of therapy and following 2 cycles of therapy (up to 8 weeks after last enrollment)
description: Descriptive statistics will be provided.
measure: Change in Cell Proliferation
time frame: Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).
description: Descriptive statistics will be provided.
measure: Change in Co-inhibitory Receptor Expression on CD8 T Cells
time frame: Baseline prior to start of therapy and after completion of therapy (approximately 2 years after last participant enrollment).
description: Descriptive statistics will be provided.
measure: Change in Quality of Life
time frame: From baseline prior to start of treatment through the end of avelumab therapy (up to approximately 2 years)
description: Participants will self-report their quality of life through PROMIS questionnaires, either the Pediatric Profile (ages 8 to 17 years) or the Adult Profile (age 18 years or older). The change in age-normed T-scores will be reported. Mixed effect models will be performed to assess changes in quality of life over time.
arm group label: Avelumab
arm group type: Experimental
description: All participants with recurrent/refractory osteosarcoma who consent to the study.
Interventions: Avelumab and quality of life questionnaires.
intervention type: Drug
intervention name: Avelumab
description: Patients will be administered avelumab at a dose of 10 mg/kg intravenously (IV) over 60 minutes on days 1 and 15 of each cycle, with a cycle lasting 28 days. Patients will receive avelumab every 2 weeks in cycles of 28 days for up to 24 months, or 26 cycles.
arm group label: Avelumab
other name: MSB0010718C
other name: anti-PD-L1
intervention type: Other
intervention name: Questionnaires
description: To assess quality of life, patients will complete questionnaires at four time points.
arm group label: Avelumab
other name: PROMIS Pediatric Profile
other name: PROMIS Adult Profile
criteria: 
gender: All
minimum age: 12 Years
maximum age: 49 Years
healthy volunteers: No
last name: Michael W. Bishop, MD, MS
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.stjude.org
description: St. Jude Children's Research Hospital
url: http://www.stjude.org/protocols
description: Clinical Trials Open at St. Jude
responsible party type: Sponsor
mesh term: Osteosarcoma
mesh term: Avelumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: One patient changed administration schedule for C2D15 in cycle 2 due to family vacation plan. The variance in dates was submitted to IRB and the patient was approved to continue on treatment when returns from the trip.
One patient was unable to travel from Puerto Rico due to hurricane devastation. Dose C2D15 skipped in cycle 2.
Medications were given one or two day(s) earlier or later than the scheduled date for a few patients.
point of contact: 