Clinical trial NCT06040099: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: TARE
Durvalumab
Bevacizumab
Liver Cancer
Y90
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-09-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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, ablation or transplantation.
* 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From Day 1 until date of progressive disease or death [Approximately 3 years]
Secondary outcomes:
measure: Number of participants with Adverse events (AEs)
timeFrame: From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug
measure: Objective Response Rate (ORR)
timeFrame: From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years)
measure: Overall Survival (OS)
timeFrame: Day 1 to 18 months or until death (Approximately 3 years)
measure: Duration of Response (DoR)
timeFrame: Time from first documented response until documented progression (Approximately 3 years)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Trenton
country: United States
facility: Research Site
state: New Jersey
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Houston
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
Study officials:
References: