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EMERALD-2: Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment

Sponsor
AstraZeneca (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03847428
Collaborator
(none)
908
Enrollment
214
Locations
3
Arms
61.1
Anticipated Duration (Months)
4.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab alone in patients with hepatocellular carcinoma who are at high risk of recurrence.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab monotherapy or placebo as adjuvant therapy. This study will be conducted in patients with HCC who are at high risk of recurrence after curative hepatic resection or ablation.

Study Design

Study Type:
Interventional
Actual Enrollment :
908 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multi Center Study of Durvalumab Monotherapy or in Combination With Bevacizumab as Adjuvant Therapy in Patients With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Curative Hepatic Resection or Ablation
Actual Study Start Date :
Apr 29, 2019
Anticipated Primary Completion Date :
May 31, 2023
Anticipated Study Completion Date :
May 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

Durvalumab 1120 mg (Q3W) + bevacizumab 15 mg/kg (Q3W)

Drug: Durvalumab
Durvalumab IV (intravenous)
Other Names:
  • IMFINZI

    • Drug: Bevacizumab
    Bevacizumab IV (intravenous)
    Other Names:
  • AVASTIN

    		•
    Experimental: Arm B

    Durvalumab 1120 mg (Q3W) + bevacizumab placebo (Q3W)

    Drug: Durvalumab
    Durvalumab IV (intravenous)
    Other Names:
  • IMFINZI

    • Other: Placebo
    Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking
    Placebo Comparator: Arm C

    Durvalumab placebo (Q3W) + bevacizumab placebo (Q3W)

    Other: Placebo
    Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking

    Outcome Measures

    Primary Outcome Measures

    1. Recurrence-free survival (RFS) for Arm A vs Arm C [Up to 49 months after first patient randomized]

      RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first.

    Secondary Outcome Measures

    1. Recurrence-free survival (RFS) Arm B vs Arm C [Up to 49 months after first patient randomized]

      RFS (per RECIST 1.1 criteria as assessed by BICR) will be defined as the time from the date of randomization until the date of the first objective radiologic recurrence or death due to any cause, whichever occurs first.

    2. Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C [No timeframe]

      OS is defined as the time from the date of randomization until death due to any cause

    3. Recurrence-free survival at 24 months (RFS24) and 36 months (RFS36) for Arm A vs Arm C and Arm B vs Arm C [At 24 and at 36 months]

      Proportion of RFS at 24 months and at 36 months

    4. Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C [Up to 49 months after first patient randomized]

      TTR is defined as the time from the date of randomization until the date of disease recurrence

    5. Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) for Arm A vs Arm C and Arm B vs Arm C [Up to 49 months after first patient randomized]

      Time from randomization to recurrence/progression on next therapy (RFS2/PFS2)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 150 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically or cytologically (or radiologically for patients undergoing curative ablation), newly diagnosed, confirmed HCC and successfully completed curative therapy (resection or ablation)

    • Imaging to confirm disease-free status within 28 days prior to randomization

    • ECOG 0-1 at enrolment

    • Child-Pugh score of 5 or 6

    • Adequate organ and marrow function.

    Exclusion Criteria:

    • Known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC

    • Evidence of metastasis, macrovascular invasion or co-existing malignant disease on baseline imaging

    • History of hepatic encephalopathy within 12 months prior to randomization

    • Evidence, by Investigator assessment, of varices at risk of bleeding on upper endoscopy or contrast-enhanced cross-sectional imaging

    • Patients with Vp1 to Vp4 portal vein thrombosis on baseline imaging are excluded

    • Active co-infection with HBV and HDV.

    • Receipt of prior systemic anticancer therapy for HCC

    • Those on a waiting list for liver transplantation

    Contacts and Locations

    Locations

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    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Principal Investigator: Jia Fan, PhD, Liver Cancer Institute Zhongshan Hospital, Fudan University
    • Principal Investigator: Jennifer Knox, MD, Solid Tumor Medical Oncology Princess Margaret Cancer Centre

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT03847428
    Other Study ID Numbers:
    • D910DC00001
    • 2018-004105-85
    First Posted:
    Feb 20, 2019
    Last Update Posted:
    Aug 22, 2022
    Last Verified:
    Aug 1, 2022
    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:
    No
    Keywords provided by AstraZeneca
    Early stage HCC
    Durvalumab
    Bevacizumab
    Liver Cancer
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Recurrence
    Bevacizumab
    Durvalumab

    Study Results

    No Results Posted as of Aug 22, 2022