Researchers from the University College London (UCL) Cancer Institute, London, UK, and BTG 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 chemoembolization, (TACE). 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 preloaded 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, and provided a strong rationale for the locoregional delivery of this drug.
Ricky Sharma, chair of Radiation Oncology at UCL 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 preload 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 Alban Denys, professor at the department of medical radiology at CHUV. Vandetanib-eluting beads use BTG’s recently developed radiopaque bead platform, DC Bead Lumi. Beads that can be visualised 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 optimise patient treatment.
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, a press release from BTG says.