Hepatocellular CarcinomaPhase 2TRACENCT01381211
Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of Hepatocellular Carcinoma (HCC)
A Phase 2 study testing TACE-DEB and 90Y-RE in people with Hepatocellular Carcinoma, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. In only 10% - 15% of all patients with HCC, tumors are considered resectable at presentation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- TACE-DEB and 90Y-RE
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteBelgium
- Study dates
- Sep 2011to Mar 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent.
- The diagnosis HCC is confirmed by typical appearance on imaging or cytohistological evaluation (liver biopsy).
- Accurate staging:
- MRI of the liver CT-scan of the abdomen and thorax bone scintigraphy, only in case of clinical symptoms suggestive of skeletal metastases.
Who cannot join
- Hypersensitivity to doxorubicin
- Pregnancy or breastfeeding
- Age under 18 years
- Child-Pugh score >B7
- ECOG performance status (PST) > 1
- Bilirubin > 2.6 mg/dl
Show all 18Show fewer
- AST/ALT >5x upper limit of normal (ULN)
- >50% of liver involvement
- Main portal vein (right, left or common trunk) thrombosis
- Extra-hepatic disease
- Previous treatment of study target lesions
- 99mTc-labelled macroaggregated albumin (99mTc-MAA) scintigraphy shows lack of MAA uptake in tumor (photopenic lesion)
- Activity > 610 MBq and activity reduction would imply a liver target dose > 80 Gy
- patients who are declared incompetent or suffering from physic disorders that make a comprehensive judgement impossible, such as psychosis.
- Unmanageable intolerance for contrast medium
- Life expectancy < 3 months or otherwise impossible follow-up
- Inadequate bone marrow, liver and/or renal function
- other contraindications to hepatic embolization procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of HCC: A Multicenter Randomized Controlled Trial (TRACE Trial)
Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. In only 10% - 15% of all patients with HCC, tumors are considered resectable at presentation. In contrast to metastatic liver disease, there is no role for systemic chemotherapy in the treatment of HCC. Today only evidence is available for Sorafenib, a tyrosine kinase inhibiting agent. The arsenal of non-surgical therapies can roughly be divided into local ablative, transarterial and systemic therapies. In well selected patients, local ablative therapy can offer favorable long term results.
For patients with disease confined to the liver, but locally more advanced, transarterial treatment modalities are proposed. These therapies exploit the dual blood supply to the liver. HCC derives its blood supply almost entirely from the hepatic artery, while liver parenchyma derives > 75% of its blood supply from the portal vein. Antitumoral agents, such as cytotoxic drugs or radionuclides, can be delivered in close proximity of the tumor.
Read more
Examples of transarterial therapies are: transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial chemoembolization with drug eluting beads (TACE-DEB) and transarterial radioembolization with Iodine-131 or Yttrium-90.
TACE is currently the gold standard for treatment of patients with intermediate stage HCC, with a reported median survival of around 17 months. A novel development in the TACE treatment for HCC is the drug-eluting bead (DEB). Recently performed small clinical trials reported the efficacy of DEBs in the treatment of intermediate stage HCC, which is substantially higher compared to conventional TACE.
Yttrium-90 radioembolization (90Y-RE) is a relatively recently developed technique which implements transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor.
In this study the investigators want to prospectively compare TACE-DEB and 90Y-RE, two novel treatments that both have theoretical and/or proven advantages compared to the use of conventional TACE, in patients with intermediate stage HCC.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- TACE-DEB, 90Y-RE
- Keywords
- Intermediate stage hepatocellular carcinoma
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TACE-DEBDrug
Transcatheter arterial chemoembolization (TACE) is performed with drug eluting beads (DEB), polyvinyl alcohol-based microspheres loaded with the chemotherapeutic agent doxorubicin.
90Y-REDrug
Glass Yttrium-90 microspheres (TheraSphere®; MDS Nordion Inc.) will be used
| Study group | Role | What they receive |
|---|---|---|
| Yttrium-90 radioembolization (90Y-RE) | Active comparator | Not described Receives: Drug: 90Y-RE |
| Transarterial chemoembolization with drug eluting beads | Active comparator | Transarterial chemoembolization is performed with drug eluting beads, polyvinyl alcohol-based microspheres (DC Beads, Biocompatibles) loaded with the chemotherapeutic agent doxorubicin. Receives: Drug: TACE-DEB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression (TTP).
Tumor progression is defined according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) response evaluation criteria. The mRECIST evaluation criteria define progressive disease by the implication of target lesions response, non-target lesions response and the occurrence of new lesions.
Measured: Patients will be followed over a 2 years period.
Secondary outcomes (6)
Time to Local Progression (TLP).
In both study arms, treatment is done selectively for the lesions within the perfusion area (may be lobar, segmental or subsegmental), as visualized with Cone-Beam CT prior to intervention.
Measured: Since start of treatment untill local tumor progression with a maximum of 2 years follow up.
Survival of patients dedicated to either treatment arm.
Survival of patients is followed.
Measured: Patients are followed for up to 2 years.
Quality of life EQ5D
Quality of life as measured with The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) scale, The Short Form (36) Health Survey, EuroQol Group 5-Dimension Self-Report Questionnaire score (EQ5D) and European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ30).
Measured: Before treatment and after treatment on a 3 monthly interval during 2 years.
Tumor response to therapy according to mRECIST criteria
European Association for the Study of the Liver (EASL) response will be obtained based on the following: complete response, partial response, stable disease.
Measured: Before treatment and after treatment on a 3 monthly interval during 2 years.
Treatment-related costs.
Treatment-related costs, in terms of cost of therapy and number of hospitalization days, in these patients.
Measured: After follow up of 2 year.
Toxicities and adverse events (recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0)
The number of patients with AEs, SAEs and SUSARs and the total number of AEs, SAEs and SUSARs in both treatment groups.
Measured: 6 months following last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startSep 2011
- Primary completionMar 2018
- Study completionMar 2020
Why it stopped: based on interim analysis results
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luc Defreyne, MD, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01381211
- Sponsor's protocol ID
- 2011/050
- Acronym
- TRACE
- Status last verified
- Sep 2019
- First submitted
- 14 Jun 2011
- Last updated
- 15 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Dhondt E, Lambert B, Hermie L, Huyck L, Vanlangenhove P, Geerts A, Verhelst X, Aerts M, Vanlander A, Berrevoet F, Troisi RI, Van Vlierberghe H, Defreyne L. 90Y Radioembolization versus Drug-eluting Bead Chemoembolization for Unresectable Hepatocellular Carcinoma: Results from the TRACE Phase II Randomized Controlled Trial. Radiology. 2022 Jun;303(3):699-710. doi: 10.1148/radiol.211806. Epub 2022 Mar 8.
PubMed 35258371Seinstra BA, Defreyne L, Lambert B, Lam MG, Verkooijen HM, van Erpecum KJ, van Hoek B, van Erkel AR, Coenraad MJ, Al Younis I, van Vlierberghe H, van den Bosch MA. Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial. Trials. 2012 Aug 23;13:144. doi: 10.1186/1745-6215-13-144.
PubMed 22913492
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transarterial RAdioembolization Versus ChemoEmbolization for the Treatment of HCC: A Multicenter Randomized Controlled Trial (TRACE Trial)
- ClinicalTrials.gov ID
- NCT01381211
- Acronym / sponsor ID
- TRACE / 2011/050
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Intermediate stage hepatocellular carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: based on interim analysis results
- Enrolment
- 72 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Study start
- Sep 2011 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 27 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. In only 10% - 15% of all patients with HCC, tumors are considered resectable at presentation. In contrast to metastatic liver disease, there is no role for systemic chemotherapy in the treatment of HCC. Today only evidence is available for Sorafenib, a tyrosine kinase inhibiting agent. The arsenal of non-surgical therapies can roughly be divided into local ablative, transarterial and systemic therapies. In well selected patients, local ablative therapy can offer favorable long term results.
For patients with disease confined to the liver, but locally more advanced, transarterial treatment modalities are proposed. These therapies exploit the dual blood supply to the liver. HCC derives its blood supply almost entirely from the hepatic artery, while liver parenchyma derives > 75% of its blood supply from the portal vein. Antitumoral agents, such as cytotoxic drugs or radionuclides, can be delivered in close proximity of the tumor.
Examples of transarterial therapies are: transarterial chemoembolization (TACE), bland transarterial embolization (TAE), transarterial chemoembolization with drug eluting beads (TACE-DEB) and transarterial radioembolization with Iodine-131 or Yttrium-90.
TACE is currently the gold standard for treatment of patients with intermediate stage HCC, with a reported median survival of around 17 months. A novel development in the TACE treatment for HCC is the drug-eluting bead (DEB). Recently performed small clinical trials reported the efficacy of DEBs in the treatment of intermediate stage HCC, which is substantially higher compared to conventional TACE.
Yttrium-90 radioembolization (90Y-RE) is a relatively recently developed technique which implements transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor.
In this study the investigators want to prospectively compare TACE-DEB and 90Y-RE, two novel treatments that both have theoretical and/or proven advantages compared to the use of conventional TACE, in patients with intermediate stage HCC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Yttrium-90 radioembolization (90Y-RE) | Active comparator | Drug: 90Y-RE |
| Transarterial chemoembolization with drug eluting beads | Active comparator | Drug: TACE-DEBTransarterial chemoembolization is performed with drug eluting beads, polyvinyl alcohol-based microspheres (DC Beads, Biocompatibles) loaded with the chemotherapeutic agent doxorubicin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent.
- The diagnosis HCC is confirmed by typical appearance on imaging or cytohistological evaluation (liver biopsy).
- Accurate staging:
- MRI of the liver CT-scan of the abdomen and thorax bone scintigraphy, only in case of clinical symptoms suggestive of skeletal metastases.
Key exclusion criteria (18 listed)
- Hypersensitivity to doxorubicin
- Pregnancy or breastfeeding
- Age under 18 years
- Child-Pugh score >B7
- ECOG performance status (PST) > 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TACE-DEBTranscatheter arterial chemoembolization (TACE) is performed with drug eluting beads (DEB), polyvinyl alcohol-based microspheres loaded with the chemotherapeutic agent doxorubicin. | Drug | Transarterial chemoembolization with drug eluting beads |
| 90Y-REGlass Yttrium-90 microspheres (TheraSphere®; MDS Nordion Inc.) will be used | Drug | Yttrium-90 radioembolization (90Y-RE) |
Primary outcome
Time to Progression (TTP).
Time frame: Patients will be followed over a 2 years period.
Tumor progression is defined according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) response evaluation criteria. The mRECIST evaluation criteria define progressive disease by the implication of target lesions response, non-target lesions response and the occurrence of new lesions.
6 secondary outcomes
Time to Local Progression (TLP).
Time frame: Since start of treatment untill local tumor progression with a maximum of 2 years follow up.
Survival of patients dedicated to either treatment arm.
Time frame: Patients are followed for up to 2 years.
Quality of life EQ5D
Time frame: Before treatment and after treatment on a 3 monthly interval during 2 years.
Tumor response to therapy according to mRECIST criteria
Time frame: Before treatment and after treatment on a 3 monthly interval during 2 years.
Treatment-related costs.
Time frame: After follow up of 2 year.
Toxicities and adverse events (recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0)
Time frame: 6 months following last treatment
Results and safety
The study was stopped early (reason given: based on interim analysis results). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2022.
- Derived from this study: PubMed 35258371Dhondt E, Lambert B, Hermie L, Huyck L, Vanlangenhove P, Geerts A, Verhelst X, Aerts M, Vanlander A, Berrevoet F, Troisi RI, Van Vlierberghe H, Defreyne L. 90Y Radioembolization versus Drug-eluting Bead Chemoembolization for Unresectable Hepatocellular Carcinoma: Results from the TRACE Phase II Randomized Controlled Trial. Radiology. 2022 Jun;303(3):699-710. doi: 10.1148/radiol.211806. Epub 2022 Mar 8.
- Derived from this study: PubMed 22913492Seinstra BA, Defreyne L, Lambert B, Lam MG, Verkooijen HM, van Erpecum KJ, van Hoek B, van Erkel AR, Coenraad MJ, Al Younis I, van Vlierberghe H, van den Bosch MA. Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial. Trials. 2012 Aug 23;13:144. doi: 10.1186/1745-6215-13-144.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luc Defreyne, MD, PhD principal investigator
University Hospital, Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TACE-DEB and 90Y-RE in people with Hepatocellular Carcinoma, run by University Hospital, Ghent at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: based on interim analysis results). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Progression (TTP). (time frame: Patients will be followed over a 2 years period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01381211, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2022.