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

Sponsor
AstraZeneca (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT06040099
Collaborator
(none)
100
1
36

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Sep 30, 2023
Anticipated Primary Completion Date :
Sep 30, 2026
Anticipated Study Completion Date :
Sep 30, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab

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

Drug: Durvalumab
Durvalumab IV (intravenous)
Other Names:
  • MEDI4736, IMFINZI
  • Drug: Bevacizumab
    Bevacizumab IV (intravenous)
    Other Names:
  • AVASTIN, ZIRABEV
  • Procedure: Transarterial Radioembolization (TARE)
    Yttrium 90 glass microspheres will be administered
    Other Names:
  • TheraSphere
  • Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [From Day 1 until date of progressive disease or death [Approximately 3 years]]

      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

    1. Number of participants with Adverse events (AEs) [From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug]

      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

    2. Objective Response Rate (ORR) [From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years)]

      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.

    3. Overall Survival (OS) [Day 1 to 18 months or until death (Approximately 3 years)]

      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.

    4. Duration of Response (DoR) [Time from first documented response until documented progression (Approximately 3 years)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT06040099
    Other Study ID Numbers:
    • D933GC00002
    First Posted:
    Sep 15, 2023
    Last Update Posted:
    Sep 15, 2023
    Last Verified:
    Sep 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by AstraZeneca
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 15, 2023