ABSTRACT: See https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-the-sonotran-platform-for-bowel-cancer-that-has-spread-to-the-liver-ceedd
Background and study aims
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, the 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 the safety of the new intervention. In Cohort 2, patients who are about to have their CRLMs removed by surgery will, on the day before, 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.
Who can participate?
Patients diagnosed with colorectal (bowel) cancer that has spread to the liver. Patients must be over 18 years of age and meet the trial’s specific eligibility criteria to participate in the study. For more information, please contact your GP or oncologist
What does the study involve?
For Cohort 1 (Safety), the researchers are looking at the safety of the SonoTran Platform intervention alone (ultrasound and particles), and no anticancer drugs will be given. During the SonoTran ‘intervention’ phase, patients will receive a long injection (called an infusion) of SonoTran Particles, and an administration of therapeutic SonoTran ultrasound using the SonoTran System. Additional blood samples will be taken for research tests on Day 1; the first sample will be taken immediately before patients receive the SonoTran Particles, and then at set timepoints after the start of the infusion - 15 minutes, 30 minutes, 45 minutes and 60 minutes. Patients will then be asked to return for a follow-up visit on weekly intervals - Day 8, Day 15 and Day 22 after the intervention and receive a physical examination, be asked about symptoms and any other medications, have weight, heart rate, temperature, pulse and blood pressure checked, and have routine blood tests. About 4 weeks after receiving the SonoTran Platform intervention, patients will have an FDG-PET-CT scan, an MRI scan and a CT scan to assess their tumour(s) and the effect of the SonoTran Platform.
In Cohort 2 (Performance), the researchers will investigate whether the SonoTran Platform (the combination of the SonoTran System and SonoTran Particles) can increase the delivery of a couple of routine anticancer drugs to the tumour. To do this the researchers will recruit 6 patients who, the day before their liver operation, will receive two anticancer drugs alone - cetuximab and irinotecan (at lower than standard doses), and another 6 who will receive the same anticancer drugs plus the SonoTran Platform intervention; and the researchers will compare how much of the drugs get into the tumour and how deep they get into the tumour. The researchers will be taking some of the tumour and normal tissue that is taken from the liver at your operation and they will look at the drug levels in the normal and tumour tissue in the liver. Once patients have received the intervention (drugs alone or drugs plus SonoTran Platform intervention), on Day 1, they will return the following day (Day 2) to have their tumour nodule(s) surgically removed from their liver; patients will undergo this procedure as they normally would in standard of care, and taking part in this study will not affect or delay the surgery. Additional blood samples will be taken for research tests on Day 1 and Day 2. Patients will then be asked to return for a follow-up visit on weekly intervals - Day 8, Day 15, Day 22 and on Day 29 (+/- 3 days) after the intervention and receive a physical examination, be asked about symptoms and any other medications, have weight, heart rate, temperature, pulse and blood pressure checked, and have routine blood tests.
Cohort 3 (Efficacy) will make a comparison of response between the two groups of patients; 12 patients will receive the administration of the SonoTran Particles and SonoTran System in addition to the anticancer drugs, and another 12 patients will receive the chemotherapy without the addition of the SonoTran Platform. All patients in Cohort 3 (Efficacy) will receive anticancer drugs that are used routinely in the treatment of metastatic colorectal cancer (mCRC) i.e. cancer that has spread elsewhere outside the bowel. This treatment involves a drug called cetuximab, which is an antibody treatment that blocks a growth factor receptor on tumour cells to help stop them from growing. Patients will also receive two chemotherapy drugs which are called irinotecan and 5-fluorouracil (5FU). The combination of these drugs is called FOLFIRI. During the ‘intervention’ phase of your study involvement, participants will attend the hospital to receive six cycles of this routine cetuximab and FOLFIRI, which will be given at standard doses, every 2 weeks for a 10-week period (six cycles in all). All patients will have a CT scan, MRI scan and PET-CT scan after three ‘cycles’ of anticancer treatment, to assess their tumour and the effect of the drugs (+/- the SonoTran Platform). These scans will be repeated after six cycles of anticancer agents, or sooner if the patient has to come off trial treatment for any other reason. For patients who are receiving chemotherapy drugs AND the SonoTran intervention, additional blood samples will be taken for research tests on every visit they receive intervention – Day 1, Day 15, Day 29, Day 43, Day 57 and Day 71 – one sample will be taken each treatment day about 30 minutes after patients start receiving the SonoTran Particles. Patients will receive a physical examination, be asked about symptoms and any other medications, have their weight, heart rate, temperature, pulse and blood pressure checked, and have routine blood tests at all visits.
