Researchers from the UCL Cancer Institute and 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.
Researchers from the UCL Cancer Institute and 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 tumour growth pathways, directly to the arteries feeding a liver tumour by pre-loading the drug on a radiopaque bead which can be visualised on CT scans. Although still at a very early stage of research, the development programme 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 tumour 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.1
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 tumour blood and lymph vessel growth and aid the development of solid tumours. They may also promote spread of the cancer to other organs and inhibit the body’s own immune response to the tumour. A phase II trial of vandetanib in patients with advanced liver cancer showed some promise,2 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.3 Beads that can be visualised with CT or fluoroscopic imaging offer the advantage of providing visible confirmation of bead location during and after the embolisation procedure, enabling real-time adjustments to optimise patient treatment.4
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 tumour in a very targeted way, an approach called loco-regional therapy. This programme 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.”
The VEROnA study is sponsored by BTG and supported by the Cancer Research UK Experimental Cancer Medicines Centre and the UCL Cancer Institute and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Patients with primary liver cancer or mCRC who meet the eligibility criteria will be offered participation in the clinical trial at University College London Hospitals NHS Foundation Trust and the Royal Free Hospital NHS Foundation Trust. Patients suitable for the VEROnA study are those scheduled to have their liver tumours removed surgically. By studying the resected tissue in great detail, and comparing it to the scans performed before the operation, researchers will be able to assess exactly where the vandetanib-eluting beads have been deposited in and around the tumours, and how much drug has been delivered to the target. In this way, the VEROnA “window of opportunity” clinical trial will assess the safety and tolerability of the new treatment and the potential it offers for treating liver cancer.
References
- Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D. and Bray, F. (2015), Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 136: E359–E386. doi:10.1002/ijc.29210.
- C. Hsu, et al. Vandetanib in patients with inoperable hepatocellular carcinoma: a phase II, randomized, double-blind, placebo-controlled study. J. Hepatol., 56 (5) (2012), pp. 1097–1103
- Preparation and Characterisation of Vandetanib-eluting Radiopaque Beads for Locoregional Treatment of Hepatic Malignancies. Hagan, A., Phillips, G.J., Lloyd, A.W., Czuczman, P., Lewis, A.L., Eur. J. Pharm. Sci., 101, 22-30, 2017.
- First Human Experience with Directly Image-able Iodinated Embolization Microbeads. Levy, E.B., Krishnasamy, V.P., Lewis, A.L., Willis, S., Macfarlane, C., Anderson, V., van der Bom, I.M., Radaelli, A., Dreher, M.R., Sharma, K.V., Negussie, A., Mikhail, A., Geschwind, J.H., Wood, B.J., Cardiovasc. Intervent. Radiol., 39(8), 1177-86, 2016.
