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A Global Study to Evaluate Transarterial Chemoembolization (TACE) in Combination With Durvalumab and Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-1)

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ClinicalTrials.gov Identifier: NCT03778957
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : September 10, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
A global study to evaluate transarterial chemoembolization (TACE) in combination with durvalumab and bevacizumab therapy in patients with locoregional hepatocellular carcinoma

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Durvalumab Drug: Bevacizumab Other: Placebo Procedure: Transarterial Chemoembolization (TACE) Phase 3

Detailed Description:
This is a randomized, double-blind, placebo-controlled, multicenter, global Phase III study to determine the efficacy and safety of transarterial chemoembolization (TACE) treatment in combination with durvalumab monotherapy or TACE given with durvalumab plus bevacizumab therapy compared to TACE therapy alone in patients with locoregional hepatocellular carcinoma not amenable to curative therapy

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Study Type : Interventional
Estimated Enrollment : 600 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, Multicenter Study of Transarterial Chemoembolization (TACE) in Combination With Either Durvalumab Monotherapy or Durvalumab Plus Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-1)
Actual Study Start Date : November 30, 2018
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : March 29, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A
Transarterial Chemoembolization (TACE) in combination with Durvalumab
Drug: Durvalumab
Durvalumab IV (intravenous)
Other Name: MEDI4736

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

Procedure: Transarterial Chemoembolization (TACE)
TACE (chemo and embolic agent injection into the hepatic artery)

Experimental: Arm B
Transarterial Chemoembolization (TACE) in combination with Durvalumab and Bevacizumab
Drug: Durvalumab
Durvalumab IV (intravenous)
Other Name: MEDI4736

Drug: Bevacizumab
Bevacizumab IV (intravenous)
Other Name: AVASTIN

Procedure: Transarterial Chemoembolization (TACE)
TACE (chemo and embolic agent injection into the hepatic artery)

Placebo Comparator: Arm C
Transarterial Chemoembolization (TACE) in combination with Placebos
Other: Placebo
Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous)

Procedure: Transarterial Chemoembolization (TACE)
TACE (chemo and embolic agent injection into the hepatic artery)




Primary Outcome Measures :
  1. Progression Free Survival (PFS) for Arm A vs Arm C [ Time Frame: Approximately 5 years ]
    PFS per Blinded Independent Central Review (BICR) assessment will be defined as the time from the date of randomization until the date of first objective disease progression or death


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) for Arm B vs Arm C [ Time Frame: Approximately 5 years ]
    PFS per Blinded Independent Central Review (BICR) assessment will be defined as the time from the date of randomization until the date of first objective disease progression or death

  2. Overall Survival (OS) [ Time Frame: Approximately 5 years ]
    OS is defined as the time from the date of randomization until death due to any cause

  3. Health status/quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30) [ Time Frame: Approximately 5 years ]
    Collection of patient reported outcome (PRO) measures to assess time to deterioration in global health status/quality of life (QoL), functioning (physical) and symptoms

  4. Disease-related symptoms measured by European Organization for Research and Treatment of Cancer (EORTC) 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) [ Time Frame: Approximately 5 years ]
    Collection of patient reported outcome (PRO) measures to assess time to deterioration in symptoms


Other Outcome Measures:
  1. Safety of Durvalumab and Bevacizumab as evaluated by summary of adverse events by treatment arm and CTCAE grade [ Time Frame: Approximately 5 years ]
  2. Immunogenicity of Durvalumab and Bevacizumab as measured by presence of anti-drug antibodies (ADAs) [ Time Frame: Approximately 5 years ]
  3. Pharmacokinetics (PK) of Durvalumab and Bevacizumab as determined by peak serum concentrations [ Time Frame: Approximately 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • No evidence of extrahepatic disease
  • Disease not amenable to curative surgery or transplantation or curative ablation but disease amenable to TACE
  • Child-Pugh score class A to B7 and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
  • Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria
  • Adequate organ and marrow function

Key Exclusion Criteria

  • Any history of nephrotic or nephritic syndrome
  • Clinically significant cardiovascular disease or history of arterioembolic event including a stroke or myocardial infarction
  • Any prior or current evidence of coagulopathy or bleeding diathesis or patients who had any kind of surgery in the past 28 days (biopsies are exempt from this exclusion)
  • History of abdominal fistula or GI perforation, non healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment
  • Patients with Vp3 and Vp4 portal vein thrombosis on baseline imaging are excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03778957


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 179 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Bruno Sangro, MD Clinica Universidad de Navarra
Principal Investigator: Riccardo Lencioni, MD FSIR EBIR University of Pisa / Miami Cancer Institute
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03778957    
Other Study ID Numbers: D933GC00001
2018-002134-20 ( EudraCT Number )
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2020
Individual Participant Data (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
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 refer 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Hepatocellular Carcinoma
TACE
Durvalumab
Bevacizumab
Liver Cancer
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Liver Diseases
Bevacizumab
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors