Phase I First-in-Human Study on the Use of Embrace Liquid Embolic for the Treatment of Hypervascular Tumors

IO Learning spoke with Gerard S. Goh, MBBS, Head of Interventional Radiology at the Alfred Hospital in Melbourne, Australia, and co-investigator of a recently published pilot study that investigated the clinical application of an aqueous polyethylene glycol-based liquid embolic (Embrace Hydrogel Embolic System; Instylla) for the treatment of benign and malignant hypervascular tumors.

What was the purpose of this study? Describe the study design and endpoint(s).

The aim of this study¹ was to investigate the safety and efficacy of Embrace, a polyethylene glycol (PEG)-based liquid embolic agent (Instylla), in the embolization of malignant and benign hypervascular tumors. This was a prospective, single-arm, multicenter, international study with 4 centers involved in Australia, New Zealand, and Taiwan.

The primary safety endpoint was the incidence of serious device and serious procedure-related adverse events (AEs) and non-target embolization. The primary effectiveness endpoint (technical success) for hypervascular tumor embolization was delivery of Embrace to the index vessel with disappearance of >90% of the targeted vascular bed as demonstrated by postprocedural angiography. The endpoint for portal vein embolization was occlusion of the portal branches to the liver segments for future resection as demonstrated by postprocedural portography.

Describe the patient population. Why did you choose these particular tumor types/size ranges for this first-in-human study?

Eight patients were enrolled (5 males and 3 females) aged between 30-85 years. The tumors embolized were 4 hepatocellular carcinomas (HCCs), 3 renal angiomyolipomas, and 1 intrahepatic cholangiocarcinoma. The study allowed enrollment of any hypervascular tumor <8 cm in maximal diameter apart from tumors supplied by the cerebral, coronary, or pulmonary circulation. As this was an early safety and efficacy trial, enrolling different tumor types allowed the demonstration of the embolic agent in treating any hypervascular tumor.

Briefly outline the study results. Were there any adverse events during the study period?

Ten embolizations were performed in 8 tumors. The tumor sizes ranged from 2.1 to 7.5 cm (median, 4.1 cm) with the feeder vessel diameter ranging from 1 to 2.3 mm (median, 2 mm). Technical success was 100%. All 8 patients reached 30-day follow-up with imaging and 6 patients reached 90-day follow-up. At 30 days, no target-vessel recanalization was observed on imaging. According to local follow-up guidelines (eg, EASL, RECIST 1.1, and mRECIST), there was stable disease in 1 HCC and partial and complete responses in the remainder of the tumors.

There were no unanticipated AEs related to the device. There were 3 serious AEs in 2 patients, none of which were deemed related to the embolization. These serious AEs included jaundice and sepsis 70 days after the portal vein embolization and 4 days before a planned hemihepatectomy for an intrahepatic cholangiocarcinoma, as well as recurrence of acute on chronic pancreatitis 73 days after embolization in another patient. There were 16 AEs in 7 patients, the majority of which consisted of expected postembolization symptoms, such as pain, vomiting/nausea, and fever.

Tell us about the Embrace Liquid Embolic System. Is there a learning curve associated with using this system? Do you have any tips or tricks to offer other interventionists when using the system?

The Embrace liquid embolic system consists of 2 hydrogel precursors (a polymer and an initiator) that are placed into 2 syringes that are then loaded into a dual-injection, frame-like device. The target vessel is selected as per normal endovascular techniques with a standard high-flow microcatheter (eg, Boston Scientific’s 2.8-Fr Direxion microcatheter). Once in place, the Instylla 1.7-Fr microcatheter is loaded via a coaxial set-up inside the standard high-flow microcatheter. The embolic agents are then introduced through the 2 microcatheters. When the precursor agents mix in the blood, they form a hydrogel.

Are there any noteworthy advantages and/or disadvantages of this system over other currently available embolization technology?

This technology offers controllable and safe delivery of a liquid embolic agent. In contrast to some existing liquid embolic agents (eg, N-butyl cyanoacrylate, aka “glue” and onyx), the hydrogel does not adhere to the catheter so there is no risk of “gluing” in the catheter. In addition, PEG has been used in multiple human applications (eg, retroperitoneal spacing applications and vascular closure devices). In preclinical studies, embolization was achieved to the equivalent of 40 μm particles,² allowing for deep embolization.

As with any first-generation device, there are always areas that things can be improved on—that is why we perform research! I have already seen several improvements with the Embrace device throughout its lifetime. The angiographic visibility of Embrace can be challenging in larger patients and this is already being improved upon, with Instylla using different ratios of contrast and embolic precursors for the other trials mentioned below.

Tell me about potential future studies on this technology. What is the next step for studying the Embrace System?

There are several trials currently enrolling to study the Embrace system. There are trials investigating the use of Embrace in the embolization of active hemorrhage (eg, in trauma patients) as well as a global randomized multicenter clinical trial, both of which involve my team. While we cannot share any information at this stage, I know that many are eagerly looking forward to seeing the early results of these trials.

Any final thoughts on the Embrace System or liquid embolics in general?

Liquid embolics have several advantages over other embolic agents. They allow for deep tissue penetration and embolization in some patients with coagulopathy where other embolic agents, such as coils or particles, may not work. The new-generation liquid embolic Embrace holds promise for offering controllable and safe embolization, improving on many areas of the current liquid embolic agents.

From the Department of Radiology, The Alfred Hospital, Melbourne, Australia & Monash University, Melbourne, Australia.

Address for Correspondence: Gerard S. Goh, MBBS, Department of Radiology, The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia. Email: G.Goh@alfred.org.au

References

1. Goh GS, Goodwin MD, Huang JF, Kavnoudias H, Holden A. A phase I first in human study of Embrace™ a polyethylene glycol based liquid embolic in the embolization of malignant and benign hypervascular tumors. J Vasc Interv Radiol. 2022;33(6):660-667. Epub 2022 Mar 9. doi:10.1016/j.jvir.2022.02.021

2. Ganguli S, Lareau R, Jarrett T, Soulen MC. A water-based liquid embolic: evaluation of its safety and efficacy in a rabbit kidney model. J Vasc Interv Radiol. 2021;32(6):813-818. Epub 2021 Mar 4. doi:10.1016/j.jvir.2021.02.018