CEeDD: Sonosensitive particles and ultrasound to enhance drug delivery
Research type
Research Study
Full title
CEeDD: A First-in-Human Clinical Investigation of Cavitation-Enhanced Drug Delivery to Solid Tumours by co-Administration of Sonosensitive Particles and Application of Extracorporeal Ultrasound in Patients with Colorectal Metastases to the Liver
IRAS ID
289760
Contact name
Rachel Kerr
Contact email
Sponsor organisation
University of Oxford, Clinical Trials and Research Governance Team
ISRCTN Number
17598292
Duration of Study in the UK
2 years, 2 months, 31 days
Research summary
Summary of Research
This study will look at a new intervention in patients with bowel cancer that has spread to the liver (called colorectal cancer liver metastases (CRLM)). This is required because bowel cancer is very common, and despite best efforts, once CRLM are present, chances of cure are small. The planned intervention combines specialist ultrasound treatment delivered to the body through the skin over the liver area (SonoTran System), and the injection of microscopic cup-shaped ‘particles’ (SonoTran Particles) that are given into the vein. The hope is that when these two are delivered together (termed the SonoTran Platform) they will help ‘push’ standard cancer drugs deeper into the tumours and increase the effectiveness of those drugs (both standard chemotherapy drugs, and newer larger cancer antibody drugs). The study is split into three parts. In the first part (cohort 1) patients who have received all standard drugs for their bowel cancer, or who are having a break off standard drugs, will receive one ‘treatment’ with the specialist ultrasound (called SonoTran System-SS) and one injection of the SonoTran Particles(SP), in order to assess safety of the new intervention. In Cohort 2, patients who are about to have their CRLMs removed by surgery will, the day prior, receive one low dose each of the anticancer drugs irinotecan and cetuximab and, in addition, half of the patients will receive an injection of SonoTran Particles and a single ’treatment’ with SonoTran ultrasound. The tumours (CRLMs) that are removed will be examined to see how much and how deep the drugs get into them. In Cohort 3, patients who have not yet received treatment for their CRLMs will receive repeated cycles of standard chemotherapy drugs (5-fluoruracil, irinotecan and cetuximab) and half of them will also receive SonoTran particles and SonoTran Ultrasound. Tumour responses will be measured and compared.
Summary of Results
This clinical trial investigated the safety and feasibility of a new technology called SonoTran, which uses tiny particles and ultrasound waves to help anticancer drugs reach tumours more precisely. The study was divided into three parts, each focusing on a different aspect of the intervention.
The first part looked at the overall safety and feasibility of SonoTran. Nine participants received a single dose of SonoTran particles without any cancer drugs. During the procedure, the feasibility of the technology was measured in real time, allowing doctors to monitor how well the intervention was working as it happened. This real-time feedback was also shared with the patient, so both the medical team and the patient could see the success of the intervention as it progressed. No serious side effects were reported, and the technology worked as expected in all patients. Because of these positive results, the lowest dose tested was chosen for use in the rest of the trial.
The second part of the study examined how well SonoTran improved the delivery and distribution of anticancer drugs to tumours. Seven participants with liver tumours from bowel cancer, who were scheduled for surgery to remove their tumours, were given lower doses of two common anticancer drugs, cetuximab and irinotecan. Some received these drugs with SonoTran, while others received the drugs without it. Researchers measured how much of the drugs reached different areas of the tumours and the surrounding healthy liver tissue. The results showed that patients treated with SonoTran had higher levels of the drugs in certain parts of the tumours, especially around the edges. Importantly, when the removed tissue was examined, there was no sign that SonoTran caused any damage to the cells or blood vessels, confirming that the intervention is safe at the tissue level.
The third part of the study assessed early signs of SonoTran’s impact. Ten participants received at least three cycles of standard cancer treatment. Seven of these also received SonoTran during each treatment cycle, while three did not. After treatment, scans showed that tumours shrank in 86 percent of the patients who received SonoTran, compared to 67 percent of those who did not.
Overall, these results suggest that SonoTran is safe, does not harm healthy tissue, and may help anticancer drugs reach tumours more effectively, resulting in a higher rate of tumour shrinkage. Further studies involving larger groups of patients are needed to confirm these encouraging findings.REC name
North of Scotland Research Ethics Committee 1
REC reference
21/NS/0090
Date of REC Opinion
31 Jul 2021
REC opinion
Favourable Opinion