Researchers from the UCL Cancer Institute and the specialist healthcare company BTG plc have begun the first clinical trial of an experimental treatment for liver cancer using X-ray imageable microscopic beads loaded with a targeted anti-cancer drug placed directly in the liver. The trial will evaluate delivering a precisely controlled dose of vandetanib, an inhibitor of multiple tumor growth pathways, directly to the arteries feeding a liver tumor by pre-loading the drug on a radiopaque bead which can be visualized on CT scans.

Although still at a very early stage of research, the development program aims to improve current treatments for patients with primary liver cancer and metastatic Colorectal Cancer (mCRC).

The current standard of care for liver cancer patients is known as transarterial chemoembolisation, or TACE, and involves injecting beads through an artery using a microcatheter to block the tumour-feeding blood vessels, starving the tumour of oxygen and nutrients. These beads are usually loaded with a chemotherapy drug that is released over time directly at the tumor site, avoiding exposure to the rest of the body and reducing side effects. Despite advances in this procedure, liver cancer remains one of the most common causes of cancer death worldwide.

To improve the treatment of patients with primary liver cancer and mCRC, the beads used in the VEROnA study (vandetanib-eluting radiopaque beads in patients with resectable liver malignancies) are pre-loaded with a multi-kinase inhibitor called vandetanib. Vandetanib targets genetic alterations and cell-signalling pathways that lead to liver cancer growth, recurrence, and metastasis.

These pathways, including vascular endothelial growth factors (VEGF-A and C) and epidermal growth factor receptor (EGFR), stimulate new tumor blood and lymph vessel growth, and aid the development of solid tumors.

They may also promote spread of the cancer to other organs and inhibit the body’s own immune response to the tumor. A phase II trial of vandetanib in patients with advanced liver cancer showed some promise, and provided a strong rationale for the loco-regional delivery of this drug.

Professor Ricky Sharma, chair of radiation oncology at University College London and the study’s primary investigator, said: “The incidence and mortality rates for primary liver cancer continue to climb and it is vital that we explore new treatment approaches. This research is exciting because it is the first time we have been able to pre-load a targeted cancer drug on to an imageable bead, to deliver the targeted drug in high doses to the cancer and see exactly how well the beads reach the target we have defined.  By refining the treatment using information from this clinical trial, we may be able to develop a liver-directed treatment as a superior alternative to the rather poorly-tolerated drug treatments we currently offer patients with this type of cancer.”

The vandetanib-eluting bead was developed in collaboration with Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland and Dr Alban Denys, professor at the department of medical radiology at CHUV. Vandetanib-eluting beads use BTG’s recently-developed radiopaque bead platform. Beads that can be visualized with CT or fluoroscopic imaging offer the advantage of providing visible confirmation of bead location during and after the embolization procedure, enabling real-time adjustments to optimize patient treatment.

Melanie Lee, chief scientific officer at BTG said: “As leaders in Interventional Oncology, we are continuing to pursue better solutions for patients through innovation. Our suite of products are used to treat different stage cancers and they are delivered into the cancer tumor in a very targeted way, an approach called loco-regional therapy. This program is at a very early stage of research, but testing vandetanib-eluting beads in man is an exciting milestone. Bringing to market the first embolic beads visible under X-ray imaging has enabled increased control and precision during treatment, and adding a targeted anti-cancer agent we may be able to offer a new option for hard to treat cancers in the liver.”