Trial · NCT02181075
Targeted Chemotherapy Using Focused Ultrasound for Liver Tumours
NCT02181075, Phase 1, Completed, University of Oxford; results first posted 2019-06-24
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Targeted Chemotherapy Using Focused Ultrasound for Liver Tumours. Trials, record NCT02181075. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02181075
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Targeted Chemotherapy Using Focused Ultrasound for Liver Tumours
- NCT number
- NCT02181075
- Status
- Completed
- Phases
- Phase 1
- Enrollment
- 10 participants, actual
- Lead sponsor
- University of Oxford
- Conditions
- Liver Tumour
- Interventions
ThermoDox® (LTLD), Focused Ultrasound of Target Liver Tumour, Pre-LTLD Biopsy of Target Liver Tumour, Post-LTLD Biopsy of Target Liver Tumour, Post-LTLD+FUS (Post-FUS) Biopsy of Target Liver Tumour, Thermometry of Target Tumour
- First posted
- 2014-07-03
- Last updated
- 2019-07-22
- Other registries' IDs
- eudract:2014-000514-61
- Results first posted
- 2019-06-24
- Limitations and caveats
- Key Lancet Oncology paper (detailed in References section) addresses these limitations:~1. Laboratory limitations not detailed e.g. under/over estimates~2. Tertiary endpoints not presented
Source ClinicalTrials.gov
Registered outcomes6
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Concentration of Total Intratumoral Doxorubicin in Liver Tumour (Biopsies) Following Targeted Release of Doxorubicin From ThermoDox® ('Drug') Using Mild Hyperthermia Generated Non-invasively by Focused Ultrasound (FUS) | Post-intervention sample (Day 1) compared to pre-intervention sample (Day 1) | Analytical chemistry (High Performance Liquid Chromatography) for total doxorubicin (including both released and unreleased forms) was performed on section of intratumoral biopsy samples in Good Clinical Practice Laboratory, using a validated assay. Doxorubicin concentration was evaluated in biopsy samples both post-LTLD and post-LTLD+FUS. Tumour samples were not analysed same day and were frozen at -80\^oC for subsequent analysis. Required to evaluate the primary endpoint. |
| Primary | Patients Demonstrating >Two-fold Increase in the Amount of Intratumoural Doxorubicin Before and After Focused Ultrasound | Post-LTLD+FUS sample (Day 1) compared to Post-LTLD sample (Day 1) | To satisfy the primary endpoint, a demonstrable two-fold increase in\*, or value exceeding 10μg/g of, the concentration of intra-tumoural doxorubicin at the treated tumour site following FUS-induced mild hyperthermia, was required in at least 50% of evaluable participants. \* As per the a priori protocol design, in Part II the biopsy prior to FUS-induced mild hyperthermia is not performed and therefore the average value for all evaluable tumours receiving intervention in Part I is used as a comparison for the two-fold increase from pre-FUS to post-FUS biopsy. |
| Secondary | (Part I Only) Achievement of Satisfactory Hyperthermia Within the Target Liver Tumour for a Range of Participant Body Mass Indices (BMIs) and Tumour Locations Within the Liver (Optimal FUS Exposure Parameters) | Real-time thermometry monitoring during intervention (Day 1) | Achievement of hyperthermia in the target liver tumour, as determined by real-time thermometry obtained by an indwelling thermometry device. For success, sustained and controlled hyperthermia is required in the target tumour, consequent with drug release (in excess of 39.5\^oC). Real time thermometry plots for each Part I patient are available in the key Lancet Oncology publication, details available in the References section. |
| Secondary | Persistence of Cell Viability Stain Post-LTLD+FUS | Tissue obtained on day of intervention (Day 1). All CK8 cell viability staining was performed within 2 months of sampling. | Post-LTLD+FUS tissue from the targeted liver tumours was obtained by biopsy at the time of the intervention, between 24/03/2015 and 29/03/2017. Cytokeratin-8 (CK-8) is a cell viability marker which if present, demonstrates lack of ablative cell death by any ablative modality, including FUS. Not all histological cell types express CK8, thus if the Post-LTLD+FUS it may either indicate: i) Non-CK8 expression ii) Thermal ablation and consequent cell death. Note there was uncertainty about CK8 expression of individual patient tumours prior to recruitment. In this study if the Post-LTLD+FUS tissue shows specific cellular CK8 cellular staining, then it demonstrates that i) the tumour is CK8+, and, ii) the tumour was not instantaneously thermally ablated and any subsequent cell death is likely due to drug delivery/chemo-ablation. For more information see key TARDOX Lancet Oncology publication and Cytokeratin 8 reference (both detailed in References section). |
| Secondary | Patients With Significant (Grade 3-5) Adverse Event(s) Deemed Related to ThermoDox (LTLD) | Up to 30 days post-intervention (Day 1-30) | Adverse Events are listed separately in the subsequent results, but were also specified as a secondary endpoint in the a priori protocol and thus significant events are summarised here. 'Definitely' or 'Probably' related events are included. |
| Secondary | Patients With Significant (Grade 3-5) Adverse Event(s) Deemed Related to FUS Procedure | Up to 30 days post-intervention (Day 1-30) | Adverse Events are listed separately in the subsequent results, but were also specified as a secondary endpoint in the a priori protocol and thus significant events are summarised here. 'Definitely' or 'Probably' related events are included. |
Source ClinicalTrials.gov
Outcomes6
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Concentration of Total Intratumoral Doxorubicin in Liver Tumour (Biopsies) Following Targeted Release of Doxorubicin From ThermoDox® ('Drug') Using Mild Hyperthermia Generated Non-invasively by Focused Ultrasound (FUS) | Post-intervention sample (Day 1) compared to pre-intervention sample (Day 1) | ug/g of total doxorubicin(tumour biopsy) | MEAN | |
| PRIMARY | Patients Demonstrating >Two-fold Increase in the Amount of Intratumoural Doxorubicin Before and After Focused Ultrasound | Post-LTLD+FUS sample (Day 1) compared to Post-LTLD sample (Day 1) | Participants | COUNT_OF_PARTICIPANTS | |
| SECONDARY | (Part I Only) Achievement of Satisfactory Hyperthermia Within the Target Liver Tumour for a Range of Participant Body Mass Indices (BMIs) and Tumour Locations Within the Liver (Optimal FUS Exposure Parameters) | Real-time thermometry monitoring during intervention (Day 1) | In Part II there was no real-time thermometry and this endpoint only applies to Part I patients. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Persistence of Cell Viability Stain Post-LTLD+FUS | Tissue obtained on day of intervention (Day 1). All CK8 cell viability staining was performed within 2 months of sampling. | 5/6 Part I patients and 4/4 Part II patients had tissue which was analysable for CK-8. The Outcome Measure Data Table demonstrates the number of patients from each arm having CK-8 positive tumour biopsy samples post-LTLD+FUS, indicating lack of thermal ablation (which is consistent with desired hyperthermia rather than undesirable FUS ablation). | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Patients With Significant (Grade 3-5) Adverse Event(s) Deemed Related to ThermoDox (LTLD) | Up to 30 days post-intervention (Day 1-30) | Participants | COUNT_OF_PARTICIPANTS | |
| SECONDARY | Patients With Significant (Grade 3-5) Adverse Event(s) Deemed Related to FUS Procedure | Up to 30 days post-intervention (Day 1-30) | Participants | COUNT_OF_PARTICIPANTS |
Source ClinicalTrials.gov
Results by group13
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
Concentration of Total Intratumoral Doxorubicin in Liver Tumour (Biopsies) Following Targeted Release of Doxorubicin From ThermoDox® ('Drug') Using Mild Hyperthermia Generated Non-invasively by Focused Ultrasound (FUS) | Part I (Patients Enrolled Between March 2015-April 2017) | Pre-FUS Intratumoural Doxorubicin Concentration | 2.34 | Standard Deviation 0.93 | ug/g of total doxorubicin(tumour biopsy) |
Concentration of Total Intratumoral Doxorubicin in Liver Tumour (Biopsies) Following Targeted Release of Doxorubicin From ThermoDox® ('Drug') Using Mild Hyperthermia Generated Non-invasively by Focused Ultrasound (FUS) | Part II (Patients Enrolled Between June 2016-Feb 2017) | Pre-FUS Intratumoural Doxorubicin Concentration | 2.34 | Standard Deviation 0.93 | ug/g of total doxorubicin(tumour biopsy) |
Concentration of Total Intratumoral Doxorubicin in Liver Tumour (Biopsies) Following Targeted Release of Doxorubicin From ThermoDox® ('Drug') Using Mild Hyperthermia Generated Non-invasively by Focused Ultrasound (FUS) | Part I (Patients Enrolled Between March 2015-April 2017) | Post-FUS Intratumoural Doxorubicin Concentration | 7.74 | Standard Deviation 4.09 | ug/g of total doxorubicin(tumour biopsy) |
Concentration of Total Intratumoral Doxorubicin in Liver Tumour (Biopsies) Following Targeted Release of Doxorubicin From ThermoDox® ('Drug') Using Mild Hyperthermia Generated Non-invasively by Focused Ultrasound (FUS) | Part II (Patients Enrolled Between June 2016-Feb 2017) | Post-FUS Intratumoural Doxorubicin Concentration | 9.8 | Standard Deviation 8.12 | ug/g of total doxorubicin(tumour biopsy) |
| Patients Demonstrating >Two-fold Increase in the Amount of Intratumoural Doxorubicin Before and After Focused Ultrasound | Part I (Patients Enrolled Between March 2015-April 2017) | 4 | Participants | ||
| Patients Demonstrating >Two-fold Increase in the Amount of Intratumoural Doxorubicin Before and After Focused Ultrasound | Part II (Patients Enrolled Between June 2016-Feb 2017) | 3 | Participants | ||
(Part I Only) Achievement of Satisfactory Hyperthermia Within the Target Liver Tumour for a Range of Participant Body Mass Indices (BMIs) and Tumour Locations Within the Liver (Optimal FUS Exposure Parameters) | Part I (July 2014-July 2017) | 5 | Participants | ||
| Persistence of Cell Viability Stain Post-LTLD+FUS | Part I (Patients Enrolled Between March 2015-April 2017) | 5 | Participants | ||
| Persistence of Cell Viability Stain Post-LTLD+FUS | Part II (Patients Enrolled Between June 2016-Feb 2017) | 3 | Participants | ||
| Patients With Significant (Grade 3-5) Adverse Event(s) Deemed Related to ThermoDox (LTLD) | Part I (Patients Enrolled Between March 2015-April 2017) | 3 | Participants |
1 to 10 of 13Source ClinicalTrials.gov
See all 13 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Part I (Patients Enrolled Between March 2015-April 2017) | 6 | |
| Overall Study | STARTED | Part II (Patients Enrolled Between June 2016-Feb 2017) | 4 | |
| Overall Study | COMPLETED | Part I (Patients Enrolled Between March 2015-April 2017) | 6 | |
| Overall Study | COMPLETED | Part II (Patients Enrolled Between June 2016-Feb 2017) | 4 | |
| Overall Study | NOT COMPLETED | Part I (Patients Enrolled Between March 2015-April 2017) | 0 | |
| Overall Study | NOT COMPLETED | Part II (Patients Enrolled Between June 2016-Feb 2017) | 0 |
Source ClinicalTrials.gov
Adverse events50
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Dysphonia | Surgical and medical procedures | Part I (Patients Enrolled Between March 2015-April 2017) | 0 | 6 | |
| other | Dysphonia | Surgical and medical procedures | Part II (Patients Enrolled Between June 2016-Feb 2017) | 1 | 4 | |
| other | Neutropenia | Blood and lymphatic system disorders | Part I (Patients Enrolled Between March 2015-April 2017) | 0 | 6 | |
| other | Neutropenia | Blood and lymphatic system disorders | Part II (Patients Enrolled Between June 2016-Feb 2017) | 1 | 4 | |
| other | Fatigue or Lethargy | General disorders | Part I (Patients Enrolled Between March 2015-April 2017) | 4 | 6 | |
| other | Fatigue or Lethargy | General disorders | Part II (Patients Enrolled Between June 2016-Feb 2017) | 2 | 4 | |
| other | Nausea | General disorders | Part I (Patients Enrolled Between March 2015-April 2017) | 2 | 6 | |
| other | Nausea | General disorders | Part II (Patients Enrolled Between June 2016-Feb 2017) | 2 | 4 | |
| other | Abdominal Pain | General disorders | Part I (Patients Enrolled Between March 2015-April 2017) | 1 | 6 | |
| other | Abdominal Pain | General disorders | Part II (Patients Enrolled Between June 2016-Feb 2017) | 2 | 4 |
1 to 10 of 50Source ClinicalTrials.gov
See all 50 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Part I (Patients Enrolled Between March 2015-April 2017) | 0 | 6 |
| Total, all-cause mortality | Part II (Patients Enrolled Between June 2016-Feb 2017) | 0 | 4 |
| Total, other adverse events | Part I (Patients Enrolled Between March 2015-April 2017) | 6 | 6 |
| Total, other adverse events | Part II (Patients Enrolled Between June 2016-Feb 2017) | 4 | 4 |
| Total, serious adverse events | Part I (Patients Enrolled Between March 2015-April 2017) | 3 | 6 |
| Total, serious adverse events | Part II (Patients Enrolled Between June 2016-Feb 2017) | 3 | 4 |
Source ClinicalTrials.gov
Papers4
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons6
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
Part I (Patients Enrolled Between March 2015-April 2017) vs Part II (Patients Enrolled Between June 2016-Feb 2017): Patients With Significant (Grade 3-5) Adverse Event(s) Deemed Related to ThermoDox (LTLD) | Trial comparisons |
| Part I (Patients Enrolled Between March 2015-April 2017) vs Part II (Patients Enrolled Between June 2016-Feb 2017): Persistence of Cell Viability Stain Post-LTLD+FUS | Trial comparisons |
Part I (Patients Enrolled Between March 2015-April 2017) vs Part II (Patients Enrolled Between June 2016-Feb 2017): Patients With Significant (Grade 3-5) Adverse Event(s) Deemed Related to FUS Procedure | Trial comparisons |
| Part I (Patients Enrolled Between March 2015-April 2017) vs Part II (Patients Enrolled Between June 2016-Feb 2017): deaths from any cause | Trial comparisons |
Part I (Patients Enrolled Between March 2015-April 2017) vs Part II (Patients Enrolled Between June 2016-Feb 2017): Patients Demonstrating >Two-fold Increase in the Amount of Intratumoural Doxorubicin Before and After Focused Ultrasound | Trial comparisons |
| Part I (Patients Enrolled Between March 2015-April 2017) vs Part II (Patients Enrolled Between June 2016-Feb 2017): serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT02181075
GET https://conductscience.org/api/trials/v1/NCT02181075/events?page=2