<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/NCT02968940</url>
  </required_header>
  <id_info>
    <org_study_id>16-01179</org_study_id>
    <nct_id>NCT02968940</nct_id>
  </id_info>
  <brief_title>Avelumab With Hypofractionated Radiation Therapy in Adults With Isocitrate Dehydrogenase (IDH) Mutant Glioblastoma</brief_title>
  <official_title>A Phase II, Open-label, Single Arm, Multicenter Study of Avelumab With Hypofractionated Radiation in Adult Subjects With Transformed IDH Mutant Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NYU Langone Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>EMD Serono</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NYU Langone Health</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>
      The purpose of this study is to test how safe and effective treatment with the combination of&#xD;
      Avelumab and radiation is for IDH mutant gliomas that have transformed to glioblastoma after&#xD;
      chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The active pharmaceutical ingredient in Avelumab (MSB0010718C) is a fully human antibody of&#xD;
      the immunoglobulin gamma-1 (IgG1) isotype that specifically targets and blocks the Programmed&#xD;
      death-ligand 1(PD-L1) for Programmed cell death protein 1 (PD-1).&#xD;
&#xD;
      Avelumab binds PD-L1 and blocks the interaction between PD-L1 and PD-1. This removes the&#xD;
      suppressive effects of PD-L1 on anti-tumor cluster of differentiation 8 (CD8)+ T cells,&#xD;
      resulting in the restoration of cytotoxic T cell response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 17, 2017</start_date>
  <completion_date type="Actual">August 29, 2019</completion_date>
  <primary_completion_date type="Actual">August 29, 2019</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>Number of Dose Limiting Toxicities</measure>
    <time_frame>Day 28</time_frame>
    <description>Subjects are evaluable for DLTs (defined in section 5.2.1.2) if they have received at least one dose of Avelumab, have completed HFRT per protocol and have completed safety assessments over the entire DLT evaluation period (days 1 through 28).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Progression-free Survival (PFS6)</measure>
    <time_frame>Month 6</time_frame>
    <description>PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival (OS)</measure>
    <time_frame>Month 12</time_frame>
    <description>OS will be determined from the time of treatment initiation until the time of death, with OS being censored at last follow-up if the patient remained alive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Progression-free Survival (PFS12)</measure>
    <time_frame>Month 12</time_frame>
    <description>PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Avelumab and hypofractionated radiation therapy(HFRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks</description>
    <arm_group_label>Avelumab and hypofractionated radiation therapy(HFRT)</arm_group_label>
    <other_name>MSB0010718C</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated radiation therapy (HFRT)</intervention_name>
    <description>Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
    <arm_group_label>Avelumab and hypofractionated radiation therapy(HFRT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects aged ≥18 years.&#xD;
&#xD;
          2. Documentation of IDH1 or IDH2 mutation in any tumor specimen.&#xD;
&#xD;
          3. Pathologic evidence (either diagnostic pathology slides or pathology report) of a&#xD;
             diagnosis of WHO grade II or III glioma prior to treatment with temozolomide or PCV&#xD;
             chemotherapy.&#xD;
&#xD;
          4. Histopathological evidence of glioblastoma (WHO grade IV) on a progressive tumor&#xD;
             specimen after treatment with temozolomide or PCV chemotherapy. The diagnosis of&#xD;
             glioblastoma must be confirmed on central review by a study-designated&#xD;
             neuropathologist at NYULMC at screening.&#xD;
&#xD;
        Exceptions to this eligibility include the following:&#xD;
&#xD;
        a. Any progressive glioma with IDH1 or IDH2 mutation, regardless of WHO grade,&#xD;
        histopathological diagnosis, or prior therapy, will be eligible if the progressive tumor&#xD;
        specimen is found to have one of the genetic alterations below:&#xD;
&#xD;
          1. ≥20 somatic mutations per Mb by whole-exome sequencing&#xD;
&#xD;
          2. High mutation burden or microsatellite instability (MSI) identified by Foundation&#xD;
             Medicine panel next-generation sequencing (FoundationOne®, FoundationOne CDx™).&#xD;
             Foundation Medicine's threshold for high mutation burden (HMB) in their panel NGS&#xD;
             assays is ≥20 somatic mutations per Mb. Foundation Medicine's panel NGS assay has been&#xD;
             validated by whole-exome and whole-genome sequencing to correlate tightly with tumor&#xD;
             mutation burden (R2 = 0.94).96&#xD;
&#xD;
          3. Mutation in a mismatch repair gene or other genes known to be associated with&#xD;
             hypermutator phenotypes or microsatellite instability, including but not limited to&#xD;
             MSH2, MSH6, MLH1, POLE, PMS2, POLD as determined by validated methods.&#xD;
&#xD;
          4. Microsatellite instability as identified by polymerase chain reaction (PCR) or other&#xD;
             validated methods.&#xD;
&#xD;
             b. Progressive oligodendroglioma (with 1p/19q codeletion) that has hallmark&#xD;
             histopathological features of glioblastoma (i.e. necrosis, pseudopalisading necrosis,&#xD;
             or microvascular proliferation) is eligible as IDH1/2 mutant, 1p/19q codeleted&#xD;
             oligodendrogliomas that have progressed after chemotherapy have been shown to develop&#xD;
             hypermutation phenotype.&#xD;
&#xD;
          5. Availability of a paraffin-embedded or frozen tumor-tissue block with a minimum of 1&#xD;
             cm2 of tumor surface area from a tissue specimen that demonstrates pathological&#xD;
             transformation to glioblastoma (WHO grade IV) or a progressive specimen that harbors&#xD;
             one of the genetic alterations specified in Inclusion Criteria 4a. a. If a tumor block&#xD;
             cannot be submitted, then 20 unstained slides (preferably 10 slides from two different&#xD;
             tumor blocks from the same surgery) from the tumor specimen must be submitted.&#xD;
&#xD;
          6. Patients must have had treatment with temozolomide, lomustine (CCNU) or PCV&#xD;
             [procarbazine, lomustine (CCNU), vincristine] chemotherapy prior to histopathologic&#xD;
             transformation to glioblastoma or prior to identification of one of the genetic&#xD;
             alterations specified in Inclusion&#xD;
&#xD;
        Criteria 4a. Notes or records from the treating oncologist are required for documentation&#xD;
        of treatment history. Prior treatment with at least one of the following chemotherapy&#xD;
        schedules is required to be eligible:&#xD;
&#xD;
          1. At least one 6 week course of continuous daily temozolomide&#xD;
&#xD;
          2. At least six 28-day cycles given in one of the following schedules:&#xD;
&#xD;
               1. Daily for 5 days of a 28-day cycle&#xD;
&#xD;
               2. Daily for 21 days of a 28-day cycle&#xD;
&#xD;
               3. Daily for 14 days of a 28-day cycle&#xD;
&#xD;
               4. Alternating 7 days on/7 days per 28-day cycle&#xD;
&#xD;
               5. Continuous daily dosing of a 28-day cycle.&#xD;
&#xD;
          3. Other schedules of temozolomide may be considered after discussion with the overall&#xD;
             Principal Investigator.&#xD;
&#xD;
          4. At least 3 cycles of PCV or lomustine (CCNU) chemotherapy. 7. Patients who received&#xD;
             anti-tumor therapy after histopathologic transformation to glioblastoma must have&#xD;
             shown unequivocal radiographic evidence of tumor progression by contrast-enhanced MRI&#xD;
             scan (or CT scan if MRI is contraindicated).&#xD;
&#xD;
             8. Patients must have had prior CNS radiotherapy for their glioma, including standard&#xD;
             doses for lowgrade or high-grade glioma as well as non-standard dose and&#xD;
             fractionation, including hypofractionated regimens, stereotactic radiosurgery, etc.&#xD;
&#xD;
             9. Patients can have had any number of prior therapies, including but not limited to&#xD;
             molecularly targeted therapies and anti-angiogenic therapies, however they must have&#xD;
             had prior chemotherapy with either temozolomide or lomustine as per Eligibility&#xD;
             Criteria 6.&#xD;
&#xD;
             10. Karnofsky performance status of ≥60. 11. Interval of at least 6 months from the&#xD;
             completion of any prior radiotherapy and registration. If patients have not passed an&#xD;
             interval of at least 6 months, they may still be eligible if they meet one or more of&#xD;
             the following criteria:&#xD;
&#xD;
        a. New areas of tumor outside the original radiotherapy fields as determined by the&#xD;
        investigator, or b. Histologic confirmation of tumor through biopsy or resection, or c.&#xD;
        Nuclear medicine imaging, MR spectroscopy, or MR perfusion imaging consistent with true&#xD;
        progressive disease, rather than pseudoprogression or radiation necrosis obtained within 28&#xD;
        days of registration AND an interval of at least 90 days between completion of radiotherapy&#xD;
        and registration.&#xD;
&#xD;
        12. The following time periods must have elapsed prior to start of study treatment, the&#xD;
        following time periods must have elapsed:&#xD;
&#xD;
          1. 5 half-lives from any investigational agent&#xD;
&#xD;
          2. 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from&#xD;
             nitrosoureas)&#xD;
&#xD;
          3. 6 weeks from antibodies&#xD;
&#xD;
          4. Prior treatment with other immune modulating agents within fewer than 4 weeks prior to&#xD;
             the first dose of Avelumab. 1. Examples of immune modulating agents include blockers&#xD;
             of CTLA-4, 4-1BB (CD137), OX-40, therapeutic vaccines, or cytokine treatments.&#xD;
&#xD;
          5. 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.&#xD;
&#xD;
             13. An interval of at least 2 weeks (to start of study agent) between prior surgical&#xD;
             resection or one week for stereotactic biopsy.&#xD;
&#xD;
             14. Adequate hematologic, hepatic, and renal function defined by absolute neutrophil&#xD;
             count ≥1.5 x 109/L, hemoglobin &gt;9 g/dL, platelet count ≥ 100 x 109/L (may have been&#xD;
             transfused), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5&#xD;
             x upper limit of normal (ULN), total bilirubin ≤1.5 x ULN, and estimated creatinine&#xD;
             clearance (CrCl) ≥ 30 mL/min according to the Cockcroft-Gault formula or local&#xD;
             institutional standard method.&#xD;
&#xD;
             15. Women of child-bearing potential (WOCBP) and men able to father a child must agree&#xD;
             to use highly effective contraception while on study drug and for 30 days after the&#xD;
             last dose of Avelumab. WOCBP must have a negative pregnancy test within 28 days of&#xD;
             initiation of dosing.&#xD;
&#xD;
        Highly effective contraceptive measures include: stable use of oral contraceptives such as&#xD;
        combined estrogen and progestogen and progestogen only hormonal contraception or other&#xD;
        prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to&#xD;
        screening; intrauterine device [IUD]; intrauterine hormone-releasing system (IUS);&#xD;
        bilateral tubal ligation; vasectomy and sexual abstinence.&#xD;
&#xD;
          1. Contraception is not required for men with documented vasectomy.&#xD;
&#xD;
          2. Postmenopausal women must be amenorrheic for at least 12 months in order not to be&#xD;
             considered of childbearing potential.&#xD;
&#xD;
          3. Pregnancy testing and contraception are not required for women with documented&#xD;
             hysterectomy or tubal ligation.&#xD;
&#xD;
             16. Willing to and capable of providing written informed consent prior to any study&#xD;
             related procedures.&#xD;
&#xD;
             17. Ability and willingness to comply with all study requirements, including scheduled&#xD;
             visits, treatment plans, laboratory tests, and other study-related procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Investigational drug use within 28 days of the first dose of Avelumab.&#xD;
&#xD;
          2. Planned participation in another study of an investigational agent or investigational&#xD;
             device or use of a therapeutic device intended for therapy of glioma.&#xD;
&#xD;
          3. Prior therapy with an agent that blocks the PD-1/PD-L1 pathway.&#xD;
&#xD;
          4. Primary brainstem or spinal cord tumor.&#xD;
&#xD;
          5. Diffuse leptomeningeal disease at recurrence&#xD;
&#xD;
          6. Recurrent infratentorial tumor&#xD;
&#xD;
          7. Prior re-irradiation or stereotactic radiosurgery for recurrent disease at the same&#xD;
             tumor location intended for HFRT in this study.&#xD;
&#xD;
          8. Maximal tumor diameter &gt;4 cm&#xD;
&#xD;
          9. Patients with evidence of significant intracranial mass effect that requires &gt;4 mg of&#xD;
             dexamethasone or bioequivalent per day for 5 consecutive days for management of&#xD;
             symptoms at any time within 14 days of registration.&#xD;
&#xD;
               1. Subjects on a standard high-dose steroid taper after craniotomy may receive a&#xD;
                  higher dose of corticosteroids within 14 days of registration, however must be at&#xD;
                  a dose ≤4 mg of dexamethasone or bioequivalent per day within 5 days prior to&#xD;
                  registration.&#xD;
&#xD;
               2. Administration of steroids through a route known to result in a minimal systemic&#xD;
                  exposure [i.e., intranasal, intraocular, inhaled, topical, or local injection&#xD;
                  (e.g., intra-articular injection) corticosteroids (&lt;5% of body surface area)] are&#xD;
                  permitted.&#xD;
&#xD;
               3. Subjects requiring hormone replacement with corticosteroids are eligible if the&#xD;
                  steroids are at doses ≤ 10 mg prednisone or bioequivalent per day.&#xD;
&#xD;
               4. Steroids as premedication for hypersensitivity reactions (e.g., CT scan&#xD;
                  premedication) are allowed.&#xD;
&#xD;
         10. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory&#xD;
             agent. The following are not exclusions:&#xD;
&#xD;
             a. Patients with diabetes type I, vitiligo, hypo- or hyperthyroid diseases, or&#xD;
             psoriasis not requiring systemic immunosuppressive treatment are eligible.&#xD;
&#xD;
         11. Prior organ transplantation, including allogeneic stem cell transplantation.&#xD;
&#xD;
         12. Known history of, or any evidence of active, non-infectious pneumonitis within the&#xD;
             last 5 years.&#xD;
&#xD;
         13. Known prior, severe hypersensitivity (NCI-CTCAE v4.03 Grade 3 or 4) to investigational&#xD;
             product or any component in its formulations including known severe hypersensitivity&#xD;
             reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma&#xD;
             (that is, 3 or more features of partially controlled asthma).&#xD;
&#xD;
         14. Active infection requiring systemic therapy.&#xD;
&#xD;
         15. Known history of testing positive for human immunodeficiency virus (HIV) or known&#xD;
             acquired immunodeficiency syndrome.&#xD;
&#xD;
         16. Positive test for Hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus&#xD;
             (HCV antibody) at screening indicating acute or chronic infection.&#xD;
&#xD;
         17. Vaccination within 4 weeks of the first dose of avelumab and while on trials is&#xD;
             prohibited except for administration of inactivated vaccines. Note: Seasonal influenza&#xD;
             vaccines for injection are generally inactivated flu vaccines and are allowed; however&#xD;
             intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are&#xD;
             not allowed.&#xD;
&#xD;
         18. 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), or serious cardiac arrhythmia requiring&#xD;
             medication.&#xD;
&#xD;
         19. Persisting toxicity related to prior therapy of Grade &gt;1 NCI-CTCAE v 4.03; however,&#xD;
             alopecia and sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a&#xD;
             safety risk based on investigator's judgment, are acceptable.&#xD;
&#xD;
         20. Patients with another active cancer [excluding basal cell carcinoma, cervical&#xD;
             carcinoma in situ or melanoma in situ]. Prior history of other cancer is allowed, as&#xD;
             long as there was no active disease within the prior 2 years.&#xD;
&#xD;
         21. Pregnant or breastfeeding (negative serum or urine pregnancy test required for women&#xD;
             of childbearing potential), or unable to maintain use of contraception while on study&#xD;
             and for 30 days after the last dose of Avelumab.&#xD;
&#xD;
         22. Known alcohol or drug abuse&#xD;
&#xD;
         23. All other unstable, severe, or chronic medical conditions including immune colitis,&#xD;
             inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric&#xD;
             conditions including recent (within the past year) or active suicidal ideation or&#xD;
             behavior; or laboratory abnormalities that may increase the risk associated with study&#xD;
             participation or study treatment administration or may interfere with the&#xD;
             interpretation of study results and, in the judgment of the investigator, would make&#xD;
             the patient inappropriate for entry into this study.&#xD;
&#xD;
         24. Any condition that would prohibit the understanding or rendering of informed consent.&#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>Sylvia Kurz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NYU Perlmutter Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, Los Angeles (UCLA)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laura &amp; Isaac Perlmutter Cancer Center &amp; NYU Langone Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <results_first_submitted>June 2, 2022</results_first_submitted>
  <results_first_submitted_qc>June 27, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 29, 2022</results_first_posted>
  <disposition_first_submitted>May 28, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>June 27, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">June 29, 2022</disposition_first_posted>
  <last_update_submitted>June 27, 2022</last_update_submitted>
  <last_update_submitted_qc>June 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Programmed cell death protein 1 (PD-1)</keyword>
  <keyword>Programmed death-ligand 1 (PD-L1)</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Hypofractionated Radiotherapy (HFRT)</keyword>
  <keyword>Isocitrate dehydrogenase (IDH)</keyword>
  <keyword>Glioma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</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>October 30, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/40/NCT02968940/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Avelumab and Hypofractionated Radiation Therapy(HFRT)</title>
          <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions&#xD;
Avelumab: Avelumab 10 mg/kg intravenously (IV) every 2 weeks&#xD;
Hypofractionated radiation therapy (HFRT): Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </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="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Avelumab and Hypofractionated Radiation Therapy(HFRT)</title>
          <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions&#xD;
Avelumab: Avelumab 10 mg/kg intravenously (IV) every 2 weeks&#xD;
Hypofractionated radiation therapy (HFRT): Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45" lower_limit="31.5" upper_limit="54.4"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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>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="5"/>
                  </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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Dose Limiting Toxicities</title>
        <description>Subjects are evaluable for DLTs (defined in section 5.2.1.2) if they have received at least one dose of Avelumab, have completed HFRT per protocol and have completed safety assessments over the entire DLT evaluation period (days 1 through 28).</description>
        <time_frame>Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Avelumab and Hypofractionated Radiation Therapy(HFRT)</title>
            <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions&#xD;
Avelumab: Avelumab 10 mg/kg intravenously (IV) every 2 weeks&#xD;
Hypofractionated radiation therapy (HFRT): Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Dose Limiting Toxicities</title>
          <description>Subjects are evaluable for DLTs (defined in section 5.2.1.2) if they have received at least one dose of Avelumab, have completed HFRT per protocol and have completed safety assessments over the entire DLT evaluation period (days 1 through 28).</description>
          <units>Events meeting DLT Criteria</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Median Progression-free Survival (PFS6)</title>
        <description>PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression</description>
        <time_frame>Month 6</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Avelumab and Hypofractionated Radiation Therapy(HFRT)</title>
            <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions&#xD;
Avelumab: Avelumab 10 mg/kg intravenously (IV) every 2 weeks&#xD;
Hypofractionated radiation therapy (HFRT): Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival (PFS6)</title>
          <description>PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression</description>
          <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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" lower_limit="1.4" upper_limit="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Overall Survival (OS)</title>
        <description>OS will be determined from the time of treatment initiation until the time of death, with OS being censored at last follow-up if the patient remained alive</description>
        <time_frame>Month 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Avelumab and Hypofractionated Radiation Therapy(HFRT)</title>
            <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions&#xD;
Avelumab: Avelumab 10 mg/kg intravenously (IV) every 2 weeks&#xD;
Hypofractionated radiation therapy (HFRT): Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
          </group>
        </group_list>
        <measure>
          <title>Median Overall Survival (OS)</title>
          <description>OS will be determined from the time of treatment initiation until the time of death, with OS being censored at last follow-up if the patient remained alive</description>
          <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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.1" lower_limit="6.8" upper_limit="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression-free Survival (PFS12)</title>
        <description>PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression</description>
        <time_frame>Month 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Avelumab and Hypofractionated Radiation Therapy(HFRT)</title>
            <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions&#xD;
Avelumab: Avelumab 10 mg/kg intravenously (IV) every 2 weeks&#xD;
Hypofractionated radiation therapy (HFRT): Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival (PFS12)</title>
          <description>PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression</description>
          <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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.2" lower_limit="1.4" upper_limit="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <desc>regular investigator assessment</desc>
      <group_list>
        <group group_id="E1">
          <title>Avelumab and Hypofractionated Radiation Therapy(HFRT)</title>
          <description>Avelumab 10 mg/kg intravenously (IV) every 2 weeks.&#xD;
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions&#xD;
Avelumab: Avelumab 10 mg/kg intravenously (IV) every 2 weeks&#xD;
Hypofractionated radiation therapy (HFRT): Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions</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="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Edema cerebral</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Other, radiation vasculopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tongue sores</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Anorectal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>CD4 lymphocytes decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Spasticity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Sinus pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pyramidal tract syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Facial nerve disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cognitive disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary urgency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal dryness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Sun burn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </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>Sylvia Kurz, MD, PhD</name_or_title>
      <organization>NYU Langone Health - Perlmutter Cancer Center</organization>
      <phone>212-731-6267</phone>
      <email>Sylvia.Kurz@nyulangone.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/NCT02968940
org study id: 16-01179
nct id: NCT02968940
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test how safe and effective treatment with the combination of
      Avelumab and radiation is for IDH mutant gliomas that have transformed to glioblastoma after
      chemotherapy.
The active pharmaceutical ingredient in Avelumab (MSB0010718C) is a fully human antibody of
      the immunoglobulin gamma-1 (IgG1) isotype that specifically targets and blocks the Programmed
      death-ligand 1(PD-L1) for Programmed cell death protein 1 (PD-1).

      Avelumab binds PD-L1 and blocks the interaction between PD-L1 and PD-1. This removes the
      suppressive effects of PD-L1 on anti-tumor cluster of differentiation 8 (CD8)+ T cells,
      resulting in the restoration of cytotoxic T cell response.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Dose Limiting Toxicities
time frame: Day 28
description: Subjects are evaluable for DLTs (defined in section 5.2.1.2) if they have received at least one dose of Avelumab, have completed HFRT per protocol and have completed safety assessments over the entire DLT evaluation period (days 1 through 28).
measure: Median Progression-free Survival (PFS6)
time frame: Month 6
description: PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression
measure: Median Overall Survival (OS)
time frame: Month 12
description: OS will be determined from the time of treatment initiation until the time of death, with OS being censored at last follow-up if the patient remained alive
measure: Median Progression-free Survival (PFS12)
time frame: Month 12
description: PFS, defined as the time between treatment initiation and first occurrence of disease progression or death, will be censored at last follow-up if the patient remained alive without disease progression
arm group label: Avelumab and hypofractionated radiation therapy(HFRT)
arm group type: Experimental
description: Avelumab 10 mg/kg intravenously (IV) every 2 weeks.
Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions
intervention type: Biological
intervention name: Avelumab
description: Avelumab 10 mg/kg intravenously (IV) every 2 weeks
arm group label: Avelumab and hypofractionated radiation therapy(HFRT)
other name: MSB0010718C
intervention type: Radiation
intervention name: Hypofractionated radiation therapy (HFRT)
description: Hypofractionated radiation therapy to a total dose of 30 Gy, delivered in 6 Gy per fraction for 5 consecutive daily fractions
arm group label: Avelumab and hypofractionated radiation therapy(HFRT)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sylvia Kurz, MD
role: Principal Investigator
affiliation: NYU Perlmutter Cancer Center
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Avelumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 