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

• ClinicalTrials.gov Identifier: NCT06040099
• Recruitment Status: Not yet recruiting
• First Posted: September 15, 2023
• Last Update Posted: September 15, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: September 11, 2023
• First Posted Date: September 15, 2023
• Last Update Posted Date: September 15, 2023
• Estimated Study Start Date: September 30, 2023
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 11, 2023)

Progression Free Survival (PFS) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 11, 2023)

• Number of participants with Adverse events (AEs) [ Time Frame: 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
• Objective Response Rate (ORR) [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: 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.
• Duration of Response (DoR) [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A US Study to Evaluate Transarterial Radioembolization (TARE) in Combination With Durvalumab and Bevacizumab Therapy in People With Unresectable Hepatocellular Carcinoma Amenable to TARE
• 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
• 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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma (HCC)

Intervention

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

Study Arms

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.

Interventions:

• Drug: Durvalumab
• Drug: Bevacizumab
• Procedure: Transarterial Radioembolization (TARE)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: September 11, 2023): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2026
• Estimated Primary Completion Date: September 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT06040099
• Other Study ID Numbers: D933GC00002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

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.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• 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 deidentified 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: Not Provided
• PRS Account: AstraZeneca
• Verification Date: September 2023