xml: <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/NCT06040099</url>
    </required_header>
    <id_info>
      <org_study_id>D933GC00002</org_study_id>
      <nct_id>NCT06040099</nct_id>
    </id_info>
    <brief_title>A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE</brief_title>
    <acronym>EMERALD-Y90</acronym>
    <official_title>Phase II Single-Arm Study of Durvalumab and Bevacizumab Following Transarterial Radioembolization Using Yttrium-90 Glass Microspheres (TheraSphere™) in Unresectable Hepatocellular Carcinoma Amenable to Locoregional Therapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>AstraZeneca</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to measure the efficacy and safety of durvalumab intravenous&#xD;
        (IV) solution plus bevacizumab IV solution after transarterial radioembolization (Yttrium 90&#xD;
        glass microspheres TARE) in participants with unresectable hepatocellular carcinoma (HCC)&#xD;
        amenable to embolization.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        A Phase II single-arm study conducted in participants with unresectable Hepatocellular&#xD;
        carcinoma (HCC) eligible for embolization and not eligible for or who have declined treatment&#xD;
        with resection and/or ablation or liver transplant.&#xD;
  &#xD;
        Participants with previous Transarterial Chemoembolization (TACE) or TARE associated with the&#xD;
        curative setting are permitted with a 6-month washout.&#xD;
  &#xD;
        Approximately 125 participants with unresectable but amenable to locoregional therapy HCC&#xD;
        eligible for embolization will be enrolled in the study at approximately 20 sites in the US&#xD;
        to treat approximately 100 participants.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 30, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2026</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>Progression Free Survival (PFS)</measure>
      <time_frame>From Day 1 until date of progressive disease or death [Approximately 3 years]</time_frame>
      <description>PFS is defined as the time from Day 1 (day of TARE) until the date of progressive disease per modified Response Evaluation Criteria in Solid Tumors (mRECIST), as assessed by the investigator, or death due to any cause. It is measured to assess the efficacy of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of participants with Adverse events (AEs)</measure>
      <time_frame>From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug</time_frame>
      <description>To assess the safety of the sequence of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years)</time_frame>
      <description>ORR is defined as the proportion of participants who have a confirmed complete response or partial response, as determined by the investigator per mRECIST. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Day 1 to 18 months or until death (Approximately 3 years)</time_frame>
      <description>OS is defined as the time from the start of TARE until the date of death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DoR)</measure>
      <time_frame>Time from first documented response until documented progression (Approximately 3 years)</time_frame>
      <description>DoR is defined as the time from the date of first documented response until the date of documented progression per mRECIST as assessed by the investigator, or death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Hepatocellular Carcinoma (HCC)</condition>
    <arm_group>
      <arm_group_label>Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Durvalumab</intervention_name>
      <description>Durvalumab IV (intravenous)</description>
      <arm_group_label>Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab</arm_group_label>
      <other_name>MEDI4736, IMFINZI</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bevacizumab</intervention_name>
      <description>Bevacizumab IV (intravenous)</description>
      <arm_group_label>Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab</arm_group_label>
      <other_name>AVASTIN, ZIRABEV</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Transarterial Radioembolization (TARE)</intervention_name>
      <description>Yttrium 90 glass microspheres will be administered</description>
      <arm_group_label>Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab</arm_group_label>
      <other_name>TheraSphere</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participants with confirmed unresectable HCC&#xD;
  &#xD;
            -  Participants with Lung dose threshold for Yttrium 90 glass microspheres of 30 Gy&#xD;
               (equal or less than 30 Gy per treatment for glass) and an estimated Future liver&#xD;
               remnant volume (FLRV) ≥ 30% of whole liver volume&#xD;
  &#xD;
            -  Participants with no evidence of extrahepatic disease on any available imaging&#xD;
  &#xD;
            -  Participants with one or more measurable lesions, unilobar disease for participants&#xD;
               with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2) and eligible&#xD;
               for Yttrium 90 glass microspheres TARE.&#xD;
  &#xD;
            -  Participants having Child-Pugh score class A.&#xD;
  &#xD;
            -  Participants having ECOG performance status of 0 or 1 at enrollment&#xD;
  &#xD;
            -  Adequate organ and marrow function&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Disease amenable to curative surgery or transplantation or curative ablation.&#xD;
  &#xD;
            -  Participants co-infected with HBV and HDV&#xD;
  &#xD;
            -  Any history of nephrotic or nephritic syndrome.&#xD;
  &#xD;
            -  Clinically significant (eg, active) cardiovascular disease&#xD;
  &#xD;
            -  Participants with uncontrolled hypertension&#xD;
  &#xD;
            -  History of hepatic encephalopathy&#xD;
  &#xD;
            -  Known hereditary predisposition to bleeding or thrombosis; any prior or current&#xD;
               evidence of bleeding diathesis.&#xD;
  &#xD;
            -  Receipt of more than 1 prior embolization (TACE or TARE) treatment/procedure&#xD;
  &#xD;
            -  Participant has received any prior anticancer systemic therapy for unresectable HCC.&#xD;
  &#xD;
            -  History of arterial thrombotic event, including myocardial infarction, unstable&#xD;
               angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior&#xD;
               to enrollment.&#xD;
  &#xD;
            -  History of abdominal fistula or gastrointestinal (GI) perforation, non-healed gastric&#xD;
               ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to&#xD;
               enrollment&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>130 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>AstraZeneca Clinical Study Information Center</last_name>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 11, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>TARE</keyword>
    <keyword>Durvalumab</keyword>
    <keyword>Bevacizumab</keyword>
    <keyword>Liver Cancer</keyword>
    <keyword>Y90</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Bevacizumab</mesh_term>
      <mesh_term>Durvalumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:&#xD;
  https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.&#xD;
  Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
      <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
      <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06040099
  org study id: D933GC00002
  nct id: NCT06040099
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: Yes
  The purpose of this study is to measure the efficacy and safety of durvalumab intravenous
        (IV) solution plus bevacizumab IV solution after transarterial radioembolization (Yttrium 90
        glass microspheres TARE) in participants with unresectable hepatocellular carcinoma (HCC)
        amenable to embolization.
  A Phase II single-arm study conducted in participants with unresectable Hepatocellular
        carcinoma (HCC) eligible for embolization and not eligible for or who have declined treatment
        with resection and/or ablation or liver transplant.
  
        Participants with previous Transarterial Chemoembolization (TACE) or TARE associated with the
        curative setting are permitted with a 6-month washout.
  
        Approximately 125 participants with unresectable but amenable to locoregional therapy HCC
        eligible for embolization will be enrolled in the study at approximately 20 sites in the US
        to treat approximately 100 participants.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression Free Survival (PFS)
  time frame: From Day 1 until date of progressive disease or death [Approximately 3 years]
  description: PFS is defined as the time from Day 1 (day of TARE) until the date of progressive disease per modified Response Evaluation Criteria in Solid Tumors (mRECIST), as assessed by the investigator, or death due to any cause. It is measured to assess the efficacy of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.
  measure: Number of participants with Adverse events (AEs)
  time frame: From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug
  description: To assess the safety of the sequence of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy
  measure: Objective Response Rate (ORR)
  time frame: From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years)
  description: ORR is defined as the proportion of participants who have a confirmed complete response or partial response, as determined by the investigator per mRECIST. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.
  measure: Overall Survival (OS)
  time frame: Day 1 to 18 months or until death (Approximately 3 years)
  description: OS is defined as the time from the start of TARE until the date of death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.
  measure: Duration of Response (DoR)
  time frame: Time from first documented response until documented progression (Approximately 3 years)
  description: DoR is defined as the time from the date of first documented response until the date of documented progression per mRECIST as assessed by the investigator, or death due to any cause. It is assessed after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.
  arm group label: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
  arm group type: Experimental
  description: Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.
  intervention type: Drug
  intervention name: Durvalumab
  description: Durvalumab IV (intravenous)
  arm group label: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
  other name: MEDI4736, IMFINZI
  intervention type: Drug
  intervention name: Bevacizumab
  description: Bevacizumab IV (intravenous)
  arm group label: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
  other name: AVASTIN, ZIRABEV
  intervention type: Procedure
  intervention name: Transarterial Radioembolization (TARE)
  description: Yttrium 90 glass microspheres will be administered
  arm group label: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
  other name: TheraSphere
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 130 Years
  healthy volunteers: No
  last name: AstraZeneca Clinical Study Information Center
  phone: 1-877-240-9479
  email: information.center@astrazeneca.com
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Hepatocellular
  mesh term: Bevacizumab
  mesh term: Durvalumab
  sharing ipd: Yes
  ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
  https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
  Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
  ipd access criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
  ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home