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

• ClinicalTrials.gov Identifier: NCT03847428
• Recruitment Status: Active, not recruiting
• First Posted: February 20, 2019
• Last Update Posted: February 21, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: February 18, 2019
• First Posted Date: February 20, 2019
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: April 29, 2019
• Estimated Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 10, 2021)

Recurrence-free survival (RFS) for Arm A vs Arm C [ Time Frame: 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.

Original Primary Outcome Measures (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.

Current Secondary Outcome Measures (submitted: August 10, 2021)

• Recurrence-free survival (RFS) Arm B vs Arm C [ Time Frame: 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.
• Overall Survival (OS) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: No timeframe ]
  OS is defined as the time from the date of randomization until death due to any cause
• Recurrence-free survival at 24 months (RFS24) and 36 months (RFS36) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: At 24 and at 36 months ]
  Proportion of RFS at 24 months and at 36 months
• Time to recurrence (TTR) for Arm A vs Arm C and Arm B vs Arm C [ Time Frame: 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
• 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 49 months after first patient randomized ]
  Time from randomization to recurrence/progression on next therapy (RFS2/PFS2)

Original Secondary Outcome Measures (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: Assess Efficacy and Safety of Durvalumab Alone or Combined With Bevacizumab in High Risk of Recurrence HCC Patients After Curative 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
• 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 19, 2022): 908
• Original Estimated Enrollment (submitted: February 18, 2019): 888
• Estimated Study Completion Date: May 31, 2024
• Estimated Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 150 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Brazil, Canada, China, Egypt, France, Germany, Hong Kong, India, Italy, Japan, Korea, Republic of, Peru, Philippines, Poland, Puerto Rico, Russian Federation, Singapore, Taiwan, Thailand, Turkey, United States, Vietnam

Administrative Information

• NCT Number: NCT03847428
• Other Study ID Numbers: 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

IPD Sharing Statement

• 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

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: AstraZeneca
• Verification Date: February 2023