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

Phase 2Active Not RecruitingNCT06040099

AstraZeneca56 enrolled

Overview

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.

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 120 participants with unresectable but amenable to locoregional therapy HCC eligible for embolization will be screened in the study at approximately 20 sites in the US to enroll approximately 60 participants.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatocellular Carcinoma (HCC)

Interventions

DurvalumabDRUG

Durvalumab IV (intravenous)

BevacizumabDRUG

Bevacizumab IV (intravenous)

Transarterial Radioembolization (TARE)PROCEDURE

Yttrium 90 glass microspheres will be administered

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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 more than 1 prior embolization are permitted if more than 12 months ago, for a different primary lesion, and FLR \> 30%. * 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, ablation or transplantation. Transplant patients are considered eligible if outside of Milan criteria and not currently listed for transplant. * 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

Locations (21)

Research Site

Aurora, Colorado, United States

Research Site

Gainesville, Florida, United States

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

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.

Time frame: From Day 1 until date of progressive disease or death [Approximately 3 years]

Secondary Outcomes

Number of participants with Adverse events (AEs)

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

Time frame: From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug

Objective Response Rate (ORR)

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.

Time frame: From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years)

Overall Survival (OS)

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.

Time frame: Day 1 to 18 months or until death (Approximately 3 years)

Duration of Response (DoR)

DoR is defined as the time from the date of first documented response (that is subsequently confirmed) 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.

Data from ClinicalTrials.gov

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