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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03847428
Recruitment Status : Recruiting
First Posted : February 20, 2019
Last Update Posted : June 11, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE February 18, 2019
First Posted Date  ICMJE February 20, 2019
Last Update Posted Date June 11, 2020
Actual Study Start Date  ICMJE April 29, 2019
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2019)
Recurrence-free survival (RFS) for Arm B vs Arm C [ Time Frame: Up to 38 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2020)
  • Recurrence-free survival (RFS) Arm A vs Arm C [ Time Frame: Up to 38 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.
  • Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: At 36 (OS36) and 48 months (OS48) after first patient randomized ]
    OS is defined as the time from the date of randomization until death due to any cause
  • Recurrence-free survival at 24 months (RFS24) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 24 months ]
    Proportion of RFS at 24 months
  • Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 38 months after first patient randomized ]
    TTR is defined as the time from the date of randomization until the date of disease recurrence
  • Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 38 months after first patient randomized ]
    Time from randomization to recurrence/progression on next therapy (RFS2/PFS2)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2019)
  • Recurrence-free survival (RFS) Arm A vs Arm C [ Time Frame: Up to 38 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.
  • Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 48 months (OS48) after first patient randomized ]
    OS is defined as the time from the date of randomization until death due to any cause
  • Recurrence-free survival at 24 months (RFS24) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 24 months ]
    Proportion of RFS at 24 months
  • Recurrence-free survival at 36 months (RFS36) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 36 months ]
    Proportion of RFS at 36 months
  • Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 38 months after first patient randomized ]
    TTR is defined as the time from the date of randomization until the date of disease recurrence
  • Time from randomization to recurrence/progression on next therapy (RFS2/PFS2) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: Up to 38 months after first patient randomized ]
    Time from randomization to recurrence/progression on next therapy (RFS2/PFS2)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative Treatment
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab IV (intravenous)
    Other Name: IMFINZI
  • Drug: Bevacizumab
    Bevacizumab IV (intravenous)
    Other Name: AVASTIN
  • Other: Placebo
    Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous) or Dextrose for Durvalumab masking
Study Arms  ICMJE
  • Experimental: Arm A
    Durvalumab 1120 mg (Q3W) + bevacizumab 15 mg/kg (Q3W)
    Interventions:
    • Drug: Durvalumab
    • Drug: Bevacizumab
  • Experimental: Arm B
    Durvalumab 1120 mg (Q3W) + bevacizumab placebo (Q3W)
    Interventions:
    • Drug: Durvalumab
    • Other: Placebo
  • Placebo Comparator: Arm C
    Durvalumab placebo (Q3W) + bevacizumab placebo (Q3W)
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 18, 2019)
888
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 19, 2023
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically, 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 both HBV and HCV, or co-infected with HBV and hepatitis D virus
  • Receipt of prior systemic anticancer therapy for HCC
  • Those on a waiting list for liver transplantation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 150 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Australia,   Austria,   Brazil,   Canada,   China,   France,   Germany,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Peru,   Puerto Rico,   Taiwan,   Thailand,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03847428
Other Study ID Numbers  ICMJE D910DC00001
2018-004105-85 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified 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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account AstraZeneca
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP