Ignite Creation Date:
2024-05-06 @ 3:01 AM
Last Modification Date:
2024-10-26 @ 11:27 AM
Study NCT ID:
NCT02181075
Status:
COMPLETED
Last Update Posted:
2019-07-22
First Post:
2014-07-01
Brief Title:
Targeted Chemotherapy Using Focused Ultrasound for Liver Tumours
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official 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
Status:
COMPLETED
Status Verified Date:
2018-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TARDOX
Brief Summary:
This proof of concept study proposes targeted delivery of a broad-spectrum cytotoxic agent doxorubicin via a specially formulated LTSL ThermoDox activated by mild hyperthermia by using focused ultrasound FUS to achieve enhanced intra-tumoural doxorubicin concentrations for the same systemic dose
Adult patients with incurable confirmed hepatic primary or secondary tumours received a single cycle of LTLD followed by ultrasound-mediated hyperthermia to a single target liver tumour The primary endpoint relates to evidencing enhanced delivery of doxorubicin from LTLD at the target tumour site by comparing intratumoural concentrations of the drug before and after focused ultrasound FUS exposure
Adult patients with incurable confirmed hepatic primary or secondary tumours received a single cycle of LTLD followed by ultrasound-mediated hyperthermia to a single target liver tumour The primary endpoint relates to evidencing enhanced delivery of doxorubicin from LTLD at the target tumour site by comparing intratumoural concentrations of the drug before and after focused ultrasound FUS exposure
Detailed Description:
To date purely pharmacological approaches have failed to address what is essentially a threefold 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
Recent pre-clinical studies performed at Oxford using ThermoDox released using FUS 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 The first extracorporeal FUS device in Europe was used for a study performed at Oxford between 2002 and 2004
This single centre trial was sponsored by the University of Oxford The recruiting study site was Oxford University Hospitals NHS Trust where there is extensive clinical FUS experience
The study is split into two parts Part I identified optimal FUS exposure parameters for a range of patient BMIs and tumour locations within the liver using real time thermometry data from an implanted thermistor After at least 5 and no more than 14 participants have had the intervention using real-time thermometry data was reviewed by the Trial Management Group TMG to confirm readiness to proceed without real-time thermometry Part II which did not require thermistor implantation is designed to reflect how the therapy would be implemented in clinical practice
Participants received treatment for 1 day and are followed up for 30 days All evaluable participants from both Part I and Part II were included in the endpoint analysis Doxorubicin concentrations were directly determined from tissue biopsies of the target tumour using a Good Laboratory Practice-validated high performance liquid chromatography HPLC assay based on previously published methods
If this study demonstrates successful targeted drug delivery in human subjects using LTSLs released by mild-hyperthermia this could potentially transform the future of chemotherapy in clinical practice targeted therapy using LTSLs containing other chemotherapeutic agents triggered non-invasively by mild hyperthermia could be applied to any solid organ cancer
Recent pre-clinical studies performed at Oxford using ThermoDox released using FUS 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 The first extracorporeal FUS device in Europe was used for a study performed at Oxford between 2002 and 2004
This single centre trial was sponsored by the University of Oxford The recruiting study site was Oxford University Hospitals NHS Trust where there is extensive clinical FUS experience
The study is split into two parts Part I identified optimal FUS exposure parameters for a range of patient BMIs and tumour locations within the liver using real time thermometry data from an implanted thermistor After at least 5 and no more than 14 participants have had the intervention using real-time thermometry data was reviewed by the Trial Management Group TMG to confirm readiness to proceed without real-time thermometry Part II which did not require thermistor implantation is designed to reflect how the therapy would be implemented in clinical practice
Participants received treatment for 1 day and are followed up for 30 days All evaluable participants from both Part I and Part II were included in the endpoint analysis Doxorubicin concentrations were directly determined from tissue biopsies of the target tumour using a Good Laboratory Practice-validated high performance liquid chromatography HPLC assay based on previously published methods
If this study demonstrates successful targeted drug delivery in human subjects using LTSLs released by mild-hyperthermia this could potentially transform the future of chemotherapy in clinical practice targeted therapy using LTSLs containing other chemotherapeutic agents triggered non-invasively by mild hyperthermia could be applied to any solid organ cancer
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2014-000514-61 | EUDRACT_NUMBER | None | None |