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A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE (EMERALD-Y90)

Primary Purpose

Hepatocellular Carcinoma (HCC)

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Durvalumab
Bevacizumab
Transarterial Radioembolization (TARE)
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma (HCC) focused on measuring TARE, Durvalumab, Bevacizumab, Liver Cancer, Y90

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants with confirmed unresectable HCC Participants with Lung dose threshold for Yttrium 90 glass microspheres of 30 Gy (equal or less than 30 Gy per treatment for glass) and an estimated Future liver remnant volume (FLRV) ≥ 30% of whole liver volume Participants with no evidence of extrahepatic disease on any available imaging Participants with one or more measurable lesions, unilobar disease for participants with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2) and eligible for Yttrium 90 glass microspheres TARE. Participants having Child-Pugh score class A. Participants having ECOG performance status of 0 or 1 at enrollment Adequate organ and marrow function Exclusion Criteria: Disease amenable to curative surgery or transplantation or curative ablation. Participants co-infected with HBV and HDV Any history of nephrotic or nephritic syndrome. Clinically significant (eg, active) cardiovascular disease Participants with uncontrolled hypertension History of hepatic encephalopathy Known hereditary predisposition to bleeding or thrombosis; any prior or current evidence of bleeding diathesis. Receipt of more than 1 prior embolization (TACE or TARE) treatment/procedure Participant has received any prior anticancer systemic therapy for unresectable HCC. History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment. History of abdominal fistula or gastrointestinal (GI) perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab

    Arm Description

    Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.

    Outcomes

    Primary Outcome Measures

    Progression Free Survival (PFS)
    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.

    Secondary Outcome Measures

    Number of participants with Adverse events (AEs)
    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
    Objective Response Rate (ORR)
    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.
    Overall Survival (OS)
    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.
    Duration of Response (DoR)
    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.

    Full Information

    First Posted
    September 11, 2023
    Last Updated
    September 11, 2023
    Sponsor
    AstraZeneca
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06040099
    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
    Acronym
    EMERALD-Y90
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 30, 2023 (Anticipated)
    Primary Completion Date
    September 30, 2026 (Anticipated)
    Study Completion Date
    September 30, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    AstraZeneca

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hepatocellular Carcinoma (HCC)
    Keywords
    TARE, Durvalumab, Bevacizumab, Liver Cancer, Y90

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
    Arm Type
    Experimental
    Arm Description
    Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.
    Intervention Type
    Drug
    Intervention Name(s)
    Durvalumab
    Other Intervention Name(s)
    MEDI4736, IMFINZI
    Intervention Description
    Durvalumab IV (intravenous)
    Intervention Type
    Drug
    Intervention Name(s)
    Bevacizumab
    Other Intervention Name(s)
    AVASTIN, ZIRABEV
    Intervention Description
    Bevacizumab IV (intravenous)
    Intervention Type
    Procedure
    Intervention Name(s)
    Transarterial Radioembolization (TARE)
    Other Intervention Name(s)
    TheraSphere
    Intervention Description
    Yttrium 90 glass microspheres will be administered
    Primary Outcome Measure Information:
    Title
    Progression Free Survival (PFS)
    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.
    Time Frame
    From Day 1 until date of progressive disease or death [Approximately 3 years]
    Secondary Outcome Measure Information:
    Title
    Number of participants with Adverse events (AEs)
    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
    Time Frame
    From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug
    Title
    Objective Response Rate (ORR)
    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.
    Time Frame
    From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years)
    Title
    Overall Survival (OS)
    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.
    Time Frame
    Day 1 to 18 months or until death (Approximately 3 years)
    Title
    Duration of Response (DoR)
    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.
    Time Frame
    Time from first documented response until documented progression (Approximately 3 years)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    130 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Participants with confirmed unresectable HCC Participants with Lung dose threshold for Yttrium 90 glass microspheres of 30 Gy (equal or less than 30 Gy per treatment for glass) and an estimated Future liver remnant volume (FLRV) ≥ 30% of whole liver volume Participants with no evidence of extrahepatic disease on any available imaging Participants with one or more measurable lesions, unilobar disease for participants with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2) and eligible for Yttrium 90 glass microspheres TARE. Participants having Child-Pugh score class A. Participants having ECOG performance status of 0 or 1 at enrollment Adequate organ and marrow function Exclusion Criteria: Disease amenable to curative surgery or transplantation or curative ablation. Participants co-infected with HBV and HDV Any history of nephrotic or nephritic syndrome. Clinically significant (eg, active) cardiovascular disease Participants with uncontrolled hypertension History of hepatic encephalopathy Known hereditary predisposition to bleeding or thrombosis; any prior or current evidence of bleeding diathesis. Receipt of more than 1 prior embolization (TACE or TARE) treatment/procedure Participant has received any prior anticancer systemic therapy for unresectable HCC. History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment. History of abdominal fistula or gastrointestinal (GI) perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    AstraZeneca Clinical Study Information Center
    Phone
    1-877-240-9479
    Email
    information.center@astrazeneca.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan 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 Sharing 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 Sharing 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 Sharing URL
    https://astrazenecagroup-dt.pharmacm.com/DT/Home

    Learn more about this trial

    A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE

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