Targeted chemotherapy using focused ultrasound for liver tumours
Research type
Research Study
Full title
A Proof of Concept Study to Investigate the Feasibility of Targeted Release of Doxorubicin from Lyso-thermosensitive Liposomal (LTSL) Doxorubicin (ThermoDox®) Using Focused Ultrasound in Patients with Primary or Secondary Liver Tumours
IRAS ID
150000
Contact name
Heather House
Contact email
Sponsor organisation
R&D Department, Oxford University Hospitals NHS Trust
Eudract number
2014-000514-61
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
LTSL-504-14-101-HIF, Celsion Coorporation Protocol Number
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
To date, purely pharmacological approaches have failed to address what is essentially a three-fold challenge: (i) to deliver therapeutically significant concentrations of active agents to the tumour vasculature while minimizing off-target effects; (ii) to release the therapeutic agent ‘on-demand’ at the target site; and, (iii) to improve the distribution and spread of the therapeutic agent against the intra-tumoural pressure gradient in order to achieve a therapeutically relevant concentration throughout the tumour.
This proof of concept study proposes targeted delivery of broad-spectrum cytotoxic agent (doxorubicin), via a specially formulated Lyso-Thermosensitive Liposome (LTSL) (ThermoDox®) activated by mild hyperthermia, as both a feasible and highly efficacious solution to the drug-delivery problem for the same systemic dose.
This single centre trial is sponsored by the University of Oxford. The recruiting study site will be Oxford University Hospitals NHS Trust. Both have extensive clinical HIFU experience. The first extracorporeal HIFU device in Europe was used for a study performed at Oxford from 2002-2004.
The trial is being funded by the Oxford Biomedical Research Centre and Celsion are providing the study drug free of charge.
Recent pre-clinical studies performed at Oxford using ThermoDox® released using HIFU has shown that increased uptake at the target site is achievable. Hence there is great promise in using this combination therapy to achieve increased tumour uptake and local dose for the equivalent dose of doxorubicin used in systemic chemotherapy for human subjects, which has a well established and safe toxicity profile.
Clinical studies have demonstrated:
1. The safety profile of ThermoDox® has been shown to be consistent with that of doxorubicin (HEAT study)
2. ThermoDox® treatment markedly improves progression-free survival and overall survival in the subset of patients having optimal RFA (HEAT study)
3. ThermoDox® has demonstrated a dose-response effect against metastatic liver tumoursPatients receive treatment for 1 day and are followed up for 30 days.
REC name
North East - York Research Ethics Committee
REC reference
14/NE/0124
Date of REC Opinion
13 May 2014
REC opinion
Favourable Opinion