<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/NCT04458922</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2020-04634</org_study_id>
    <secondary_id>NCI-2020-04634</secondary_id>
    <secondary_id>000081</secondary_id>
    <secondary_id>20-C-XXXX</secondary_id>
    <secondary_id>10398</secondary_id>
    <secondary_id>10398</secondary_id>
    <nct_id>NCT04458922</nct_id>
  </id_info>
  <brief_title>Testing Atezolizumab in People 2-17 Years Old With Clear Cell Sarcoma or Advanced Chondrosarcoma</brief_title>
  <official_title>A Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Chondrosarcoma and Clear Cell Sarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</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 phase II trial studies how well atezolizumab works in treating patients with&#xD;
      chondrosarcoma or clear cell sarcoma that is newly diagnosed, cannot be removed by surgery&#xD;
      (unresectable), or has spread to other places in the body (metastatic). Immunotherapy with&#xD;
      monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the&#xD;
      cancer, and may interfere with the ability of tumor cells to grow and spread.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. Determine the objective response rates (ORR) using Response Evaluation Criteria in Solid&#xD;
      Tumors (RECIST) version (v) 1.1 of atezolizumab in adult (&gt;= 18 years) patients with clear&#xD;
      cell sarcoma (CCS) and chondrosarcoma (CS).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Determine duration of response (DOR) using RECIST v 1.1 and/or change in clinical symptoms&#xD;
      (time frame: baseline until disease progression, death, loss to follow-up, initiation of&#xD;
      another anti-cancer treatment, withdrawal of consent, or study termination).&#xD;
&#xD;
      II. Measure progression-free survival (PFS) time (time frame: baseline until disease&#xD;
      progression, death, loss to follow-up, initiation of another anti-cancer treatment,&#xD;
      withdrawal of consent, or study termination).&#xD;
&#xD;
      III. Assess the number of activated CD8+ T cells infiltrating the tumor before and after&#xD;
      atezolizumab treatment, and correlate treatment-induced changes with clinical response.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with CCS and CS on&#xD;
      atezolizumab.&#xD;
&#xD;
      II. Examine changes in PD-1/PD-L1 expression in the tumor microenvironment before and after&#xD;
      atezolizumab treatment, and correlate treatment-induced changes with clinical response.&#xD;
&#xD;
      III. Evaluate potential associations between atezolizumab activity and tumor genomic&#xD;
      alterations.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat&#xD;
      every 21 days in the absence of disease progression or unacceptable toxicity. Patients&#xD;
      undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on&#xD;
      study.&#xD;
&#xD;
      After completion of study treatment, patients are followed up to 90 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 9, 2020</start_date>
  <completion_date type="Anticipated">December 9, 2023</completion_date>
  <primary_completion_date type="Actual">November 28, 2022</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>Objective response rates (ORR)</measure>
    <time_frame>Up to 90 days after completion of treatment</time_frame>
    <description>Measured using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) or change in clinical symptoms</measure>
    <time_frame>Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination, assessed up to 3 years</time_frame>
    <description>Measured using RECIST v 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS) time</measure>
    <time_frame>Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination, assessed up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of activated CD8+ T cells infiltrating the tumor</measure>
    <time_frame>Up to 3 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Overall response</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Overall response will also be assessed using immune RECIST (iRECIST), for comparison to RECIST v1.1.</description>
  </other_outcome>
  <other_outcome>
    <measure>PD-1/PD-L1 expression in the tumor microenvironment</measure>
    <time_frame>Up to 3 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Potential associations between atezolizumab activity and tumor genomic alterations</measure>
    <time_frame>Up to 3 years</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Central Chondrosarcoma, Grade 2</condition>
  <condition>Central Chondrosarcoma, Grade 3</condition>
  <condition>Dedifferentiated Chondrosarcoma</condition>
  <condition>Metastatic Clear Cell Sarcoma of Soft Tissue</condition>
  <condition>Metastatic Primary Central Chondrosarcoma</condition>
  <condition>Unresectable Primary Central Chondrosarcoma</condition>
  <arm_group>
    <arm_group_label>Treatment (atezolizumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive atezolizumab IV over 30-60 minutes on ay 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and undergo biopsy and collection of blood samples on study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (atezolizumab)</arm_group_label>
    <other_name>MPDL 3280A</other_name>
    <other_name>MPDL 328OA</other_name>
    <other_name>MPDL-3280A</other_name>
    <other_name>MPDL3280A</other_name>
    <other_name>MPDL328OA</other_name>
    <other_name>RG7446</other_name>
    <other_name>RO5541267</other_name>
    <other_name>Tecentriq</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (atezolizumab)</arm_group_label>
    <other_name>BIOPSY_TYPE</other_name>
    <other_name>Bx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (atezolizumab)</arm_group_label>
    <other_name>Biological Sample Collection</other_name>
    <other_name>Biospecimen Collected</other_name>
    <other_name>Specimen Collection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Computed Tomography</intervention_name>
    <description>Undergo CT scan</description>
    <arm_group_label>Treatment (atezolizumab)</arm_group_label>
    <other_name>CAT</other_name>
    <other_name>CAT Scan</other_name>
    <other_name>Computed Axial Tomography</other_name>
    <other_name>Computerized Axial Tomography</other_name>
    <other_name>Computerized Tomography</other_name>
    <other_name>CT</other_name>
    <other_name>CT Scan</other_name>
    <other_name>tomography</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have documented EWSR1/ATF1 or EWSR1/CREB1 translocation or&#xD;
             histologically confirmed clear cell sarcoma, documented grade 2 or 3 conventional&#xD;
             chondrosarcoma, or documented dedifferentiated chondrosarcoma. The disease must not be&#xD;
             curable by surgery&#xD;
&#xD;
          -  Patients must have measurable disease, defined as at least one lesion that can be&#xD;
             accurately measured in at least one dimension (longest diameter to be recorded for&#xD;
             non-nodal lesions and short axis for nodal lesions) as &gt;= 20 mm (&gt;= 2 cm) by chest&#xD;
             x-ray or as &gt;= 10 mm (&gt;= 1 cm) with computed tomography (CT) scan, magnetic resonance&#xD;
             imaging (MRI), or calipers by clinical exam&#xD;
&#xD;
          -  Patients with newly diagnosed, unresectable, metastatic and measurable clear cell&#xD;
             sarcoma, EWSR1/ATF1 or EWSR1/CREB1 translocation, grade 2 or 3 conventional&#xD;
             chondrosarcoma, or dedifferentiated chondrosarcoma will also be eligible if they show&#xD;
             clinical evidence of disease progression (including history and increasing physical&#xD;
             symptoms). On-study documentation will include a physician's rationale that supports&#xD;
             evidence of clinical disease progression (i.e., increasing tumor pain)&#xD;
&#xD;
          -  Age &gt;= 2 years at the National Cancer Institute (NCI) Clinical Center (&gt;= 12 years at&#xD;
             other participating sites)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2 (Karnofsky or Lansky&#xD;
             &gt;= 70%)&#xD;
&#xD;
          -  Life expectancy of greater than 3 months&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,000/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 8 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; institutional upper limit of normal (ULN) (however, patients with&#xD;
             known Gilbert disease who have serum bilirubin level =&lt; 3 x ULN may be enrolled)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 3 x institutional ULN (AST and/or ALT =&lt; 5 x ULN for patients with liver&#xD;
             involvement)&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 2.5 x ULN (=&lt; 5 x ULN for patients with documented liver&#xD;
             involvement or bone metastases)&#xD;
&#xD;
          -  Creatinine:&#xD;
&#xD;
               -  For adult patients (&gt;= 18 years of age): &gt;= 30 mL/min/1.73 m^2 by Cockcroft-Gault&#xD;
&#xD;
               -  For pediatric patients (&lt; 18 years of age), a serum creatinine based on age and&#xD;
                  gender as follows:&#xD;
&#xD;
                    -  Age: 2 to &lt; 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) 0.8&#xD;
                       (female)&#xD;
&#xD;
                    -  Age: 6 to &lt; 10 years; Maximum serum creatinine (mg/dL): 1 (male) 1 (female)&#xD;
&#xD;
                    -  Age: 10 to &lt; 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) 1.2&#xD;
                       (female)&#xD;
&#xD;
                    -  Age: 13 to &lt; 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) 1.4&#xD;
                       (female)&#xD;
&#xD;
                    -  Age: 16 to &lt; 18 years; Maximum serum creatinine (mg/dL): 1.7 (male) 1.4&#xD;
                       (female)&#xD;
&#xD;
          -  Patients with treated brain metastases are eligible if follow-up brain imaging after&#xD;
             central nervous system (CNS)-directed therapy shows no evidence of progression for &gt;=&#xD;
             1 month after treatment of the brain metastases&#xD;
&#xD;
          -  Patients with new or progressive brain metastases (active brain metastases) or&#xD;
             leptomeningeal disease are eligible if the treating physician determines that&#xD;
             immediate CNS-specific treatment is not required and is unlikely to be required during&#xD;
             the first 2 cycles of therapy&#xD;
&#xD;
          -  Patients with a prior malignancy whose natural history or treatment does not have the&#xD;
             potential to interfere with the safety or efficacy assessment of the investigational&#xD;
             regimen are eligible for this trial&#xD;
&#xD;
          -  Patients with known history or current symptoms of cardiac disease, or history of&#xD;
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac&#xD;
             function using the New York Heart Association Functional Classification. To be&#xD;
             eligible for this trial, patients should be class 2B or better&#xD;
&#xD;
          -  Willingness to provide biopsy samples for research purposes (patients &gt;= 18 years of&#xD;
             age only)&#xD;
&#xD;
          -  Administration of atezolizumab may have an adverse effect on pregnancy and poses a&#xD;
             risk to the human fetus, including embryo-lethality. Female patients of child-bearing&#xD;
             potential and male patients must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry, for the duration of&#xD;
             study participation, and for 5 months (150 days) after the last dose of study agent.&#xD;
             Should a woman become pregnant or suspect she is pregnant while she or her partner is&#xD;
             participating in this study, she should inform her treating physician immediately&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
             or a parent/guardian able to do the same&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any prior therapy must have been completed &gt;= 4 weeks or, if known, &gt;= 5 half-lives of&#xD;
             the prior agent (whichever is shorter) prior to enrollment on protocol (minimum of 1&#xD;
             week between prior therapy and study enrollment), and the participant must have&#xD;
             recovered to eligibility levels from prior toxicity. Patients should be at least 6&#xD;
             weeks out from nitrosoureas and mitomycin C. Prior definitive radiation should have&#xD;
             been completed &gt;= 4 weeks or palliative radiation should have been completed &gt;= 2&#xD;
             weeks prior to study enrollment and all associated toxicities resolved to eligibility&#xD;
             levels (patients on study may be eligible for palliative radiotherapy to non-targeted&#xD;
             lesions after 2 cycles of therapy at the principal investigator [PI's] discretion).&#xD;
             Patients who have had prior monoclonal antibody therapy must have completed that&#xD;
             therapy &gt;= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to&#xD;
             enrollment on protocol (minimum of 1 week between prior therapy and study enrollment).&#xD;
             A patient who has received a cumulative dose of &gt; 350 mg/m^2 of anthracycline&#xD;
             (regardless of cardioprotectant) may only be enrolled if their ejection fraction&#xD;
             measured by an echocardiogram is within normal institutional limits&#xD;
&#xD;
          -  Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or&#xD;
             pathway-targeting agents&#xD;
&#xD;
               -  Patients who have received prior treatment with anti-CTLA-4 may be enrolled,&#xD;
                  provided the following requirements are met:&#xD;
&#xD;
                    -  Minimum of 12 weeks from the first dose of anti-CTLA-4 and &gt; 6 weeks from&#xD;
                       the last dose&#xD;
&#xD;
                    -  No history of severe immune-related adverse effects from anti-CTLA-4 (NCI&#xD;
                       Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)&#xD;
&#xD;
          -  Treatment with any other investigational agent within 4 weeks (or within five half&#xD;
             lives of the investigational product, whichever is shorter) prior to cycle 1, day 1&#xD;
             (minimum of 1 week between prior therapy and study enrollment). Patients must be &gt;= 2&#xD;
             weeks since any investigational agent administered as part of a phase 0 study (also&#xD;
             referred to as an &quot;early phase I study&quot; or &quot;pre-phase I study&quot; where a sub-therapeutic&#xD;
             dose of drug is administered) at the coordinating center PI's discretion, and should&#xD;
             have recovered to eligibility levels from any toxicities&#xD;
&#xD;
          -  Treatment with systemic immunostimulatory agents (including, but not limited to,&#xD;
             interferon-alpha or interleukin-2 [aldesleukin]) within 6 weeks prior to cycle 1, day&#xD;
             1&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications (including, but not limited to,&#xD;
             prednisone [ &gt; 10 mg/day], cyclophosphamide, azathioprine, methotrexate, thalidomide,&#xD;
             and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to cycle 1, day&#xD;
             1.&#xD;
&#xD;
               -  Patients who have received acute, low dose, systemic immunosuppressant&#xD;
                  medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.&#xD;
&#xD;
               -  The use of inhaled corticosteroids and systemic mineralocorticoids (e.g.,&#xD;
                  fludrocortisone) for patients with orthostatic hypotension or adrenocortical&#xD;
                  insufficiency is allowed&#xD;
&#xD;
          -  Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of&#xD;
             bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is&#xD;
             allowed&#xD;
&#xD;
          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant&#xD;
             human antibodies&#xD;
&#xD;
          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric or humanized antibodies (i.e., antibodies with generic names ending in&#xD;
             &quot;ximab&quot; or &quot;zumab&quot;, respectively) or fusion proteins&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study because atezolizumab is an investigational&#xD;
             agent with the unknown potential for teratogenic or abortifacient effects. Because&#xD;
             there is an unknown but potential risk for adverse events in nursing infants secondary&#xD;
             to treatment of the mother with atezolizumab, breastfeeding should be discontinued if&#xD;
             the mother is treated with atezolizumab&#xD;
&#xD;
          -  Patients with a history of human immunodeficiency virus (HIV)-positive on&#xD;
             antiretroviral therapy are eligible with an undetectable viral load. For those&#xD;
             patients, an HIV viral load test must be completed within 28 days prior to enrollment&#xD;
&#xD;
          -  Known clinically significant liver disease, including active viral, alcoholic, or&#xD;
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease.&#xD;
&#xD;
               -  Patients with past or resolved hepatitis B infection (defined as having a&#xD;
                  negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc&#xD;
                  [antibody to hepatitis B core antigen] antibody test) are eligible.&#xD;
&#xD;
               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if&#xD;
                  polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)&#xD;
&#xD;
          -  History or risk of autoimmune disease, including, but not limited to, systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis&#xD;
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's&#xD;
             syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune&#xD;
             thyroid disease, vasculitis, or glomerulonephritis.&#xD;
&#xD;
               -  Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid&#xD;
                  replacement hormone may be eligible&#xD;
&#xD;
               -  Patients with autoimmune hyperthyroid disease not requiring immunosuppressive&#xD;
                  treatment may be eligible&#xD;
&#xD;
               -  Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may&#xD;
                  be eligible&#xD;
&#xD;
               -  Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with&#xD;
                  dermatologic manifestations only (e.g., patients with psoriatic arthritis would&#xD;
                  be excluded) are permitted provided that they meet the following conditions:&#xD;
&#xD;
                    -  Patients with psoriasis must have a baseline ophthalmologic exam to rule out&#xD;
                       ocular manifestations&#xD;
&#xD;
                    -  Rash must cover less than 10% of body surface area (BSA)&#xD;
&#xD;
                    -  Disease is well controlled at baseline and only requiring low potency&#xD;
                       topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,&#xD;
                       fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)&#xD;
&#xD;
                    -  No acute exacerbations of underlying condition within the last 12 months&#xD;
                       (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,&#xD;
                       retinoids, biologic agents, oral calcineurin inhibitors; high potency or&#xD;
                       oral steroids)&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),&#xD;
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing&#xD;
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed&#xD;
             tomography (CT) scan. History of radiation pneumonitis in the radiation field&#xD;
             (fibrosis) is permitted&#xD;
&#xD;
          -  Patients with active tuberculosis (TB) are excluded&#xD;
&#xD;
          -  Severe infections within 4 weeks prior to cycle 1, day 1, including, but not limited&#xD;
             to, hospitalization for complications of infection, bacteremia, or severe pneumonia&#xD;
&#xD;
          -  Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1&#xD;
&#xD;
          -  Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1.&#xD;
             Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract&#xD;
             infection or chronic obstructive pulmonary disease) are eligible&#xD;
&#xD;
          -  Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of&#xD;
             need for a major surgical procedure during the course of the study&#xD;
&#xD;
          -  Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or&#xD;
             anticipation that such a live, attenuated vaccine will be required during the study&#xD;
             and up to 5 months after the last dose of atezolizumab&#xD;
&#xD;
               -  Influenza vaccination should be given during influenza season only (approximately&#xD;
                  October to March). Patients must not receive live, attenuated influenza vaccine&#xD;
                  within 4 weeks prior to cycle 1, day 1 or at any time during the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>A P Chen</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute LAO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Health Science Center - Gainesville</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital Midtown</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital/Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute Developmental Therapeutics Clinic</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NCI - Center for Cancer Research</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center-South County</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute (UPCI)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University/Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network-Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>December 10, 2022</last_update_submitted>
  <last_update_submitted_qc>December 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Chondrosarcoma</mesh_term>
    <mesh_term>Sarcoma, Clear Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page</ipd_description>
    <ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04458922
org study id: NCI-2020-04634
secondary id: NCI-2020-04634
secondary id: 000081
secondary id: 20-C-XXXX
secondary id: 10398
secondary id: 10398
nct id: NCT04458922
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well atezolizumab works in treating patients with
      chondrosarcoma or clear cell sarcoma that is newly diagnosed, cannot be removed by surgery
      (unresectable), or has spread to other places in the body (metastatic). Immunotherapy with
      monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread.
PRIMARY OBJECTIVE:

      I. Determine the objective response rates (ORR) using Response Evaluation Criteria in Solid
      Tumors (RECIST) version (v) 1.1 of atezolizumab in adult (>= 18 years) patients with clear
      cell sarcoma (CCS) and chondrosarcoma (CS).

      SECONDARY OBJECTIVES:

      I. Determine duration of response (DOR) using RECIST v 1.1 and/or change in clinical symptoms
      (time frame: baseline until disease progression, death, loss to follow-up, initiation of
      another anti-cancer treatment, withdrawal of consent, or study termination).

      II. Measure progression-free survival (PFS) time (time frame: baseline until disease
      progression, death, loss to follow-up, initiation of another anti-cancer treatment,
      withdrawal of consent, or study termination).

      III. Assess the number of activated CD8+ T cells infiltrating the tumor before and after
      atezolizumab treatment, and correlate treatment-induced changes with clinical response.

      EXPLORATORY OBJECTIVES:

      I. Compare RECIST v 1.1 versus (vs) immune RECIST (iRECIST) in patients with CCS and CS on
      atezolizumab.

      II. Examine changes in PD-1/PD-L1 expression in the tumor microenvironment before and after
      atezolizumab treatment, and correlate treatment-induced changes with clinical response.

      III. Evaluate potential associations between atezolizumab activity and tumor genomic
      alterations.

      OUTLINE:

      Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat
      every 21 days in the absence of disease progression or unacceptable toxicity. Patients
      undergo computed tomography (CT) scans and undergo biopsy and collection of blood samples on
      study.

      After completion of study treatment, patients are followed up to 90 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rates (ORR)
time frame: Up to 90 days after completion of treatment
description: Measured using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
measure: Duration of response (DOR) or change in clinical symptoms
time frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination, assessed up to 3 years
description: Measured using RECIST v 1.1.
measure: Progression-free survival (PFS) time
time frame: Baseline until disease progression, death, loss to follow-up, initiation of another anti-cancer treatment, withdrawal of consent, or study termination, assessed up to 3 years
measure: Number of activated CD8+ T cells infiltrating the tumor
time frame: Up to 3 years
measure: Overall response
time frame: Up to 3 years
description: Overall response will also be assessed using immune RECIST (iRECIST), for comparison to RECIST v1.1.
measure: PD-1/PD-L1 expression in the tumor microenvironment
time frame: Up to 3 years
measure: Potential associations between atezolizumab activity and tumor genomic alterations
time frame: Up to 3 years
arm group label: Treatment (atezolizumab)
arm group type: Experimental
description: Patients receive atezolizumab IV over 30-60 minutes on ay 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and undergo biopsy and collection of blood samples on study.
intervention type: Drug
intervention name: Atezolizumab
description: Given IV
arm group label: Treatment (atezolizumab)
other name: MPDL 3280A
other name: MPDL 328OA
other name: MPDL-3280A
other name: MPDL3280A
other name: MPDL328OA
other name: RG7446
other name: RO5541267
other name: Tecentriq
intervention type: Procedure
intervention name: Biopsy
description: Correlative studies
arm group label: Treatment (atezolizumab)
other name: BIOPSY_TYPE
other name: Bx
intervention type: Procedure
intervention name: Biospecimen Collection
description: Correlative studies
arm group label: Treatment (atezolizumab)
other name: Biological Sample Collection
other name: Biospecimen Collected
other name: Specimen Collection
intervention type: Procedure
intervention name: Computed Tomography
description: Undergo CT scan
arm group label: Treatment (atezolizumab)
other name: CAT
other name: CAT Scan
other name: Computed Axial Tomography
other name: Computerized Axial Tomography
other name: Computerized Tomography
other name: CT
other name: CT Scan
other name: tomography
criteria: 
gender: All
minimum age: 2 Years
maximum age: N/A
healthy volunteers: No
last name: A P Chen
role: Principal Investigator
affiliation: National Cancer Institute LAO
facility: 
facility: 
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facility: 
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Chondrosarcoma
mesh term: Sarcoma, Clear Cell
mesh term: Atezolizumab
mesh term: Antibodies, Monoclonal
sharing ipd: Yes
ipd description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
ipd url: https://grants.nih.gov/policy/sharing.htm