Liver NeoplasmsPhase 2TRENDYNCT02470533
Transarterial Chemoembolization Versus Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma
A Phase 2 study testing Radiation therapy and chemoembolization in people with Liver Neoplasms, run by Erasmus Medical Center at 11 sites in 3 countries.
Trial summary
Rationale: This study will compare head to head in patients with hepatocellular carcinoma (HCC) ineligible for surgery or radiofrequency ablation, the standard treatment arm, transarterial chemoembolization with drug-eluting beads (TACE-DEB), with the experimental arm, stereotactic body radiation therapy (SBRT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Neoplasms
- What is being tested?
- Radiation therapy and chemoembolization
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 30 Apr 2015to 30 Apr 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
- Patients diagnosed with HCC Patients can be included if they require treatment prior to liver transplantation.
- Barcelona Clinic Liver Cancer Stage System class A-B
- One to three tumors of maximum cumulative diameter ≤ 6 cm measured in all 3 axes.
- Measurable disease to be selected as a target on CT/MRI-scan, according to mRECIST criteria for HCC within 6 weeks prior to randomization (≥ 1cm at least in one dimension, suitable for repeated measurement, and arterial enhancement) [44].
- Tumor visibility on CT
- Child-Pugh A cirrhosis
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- Age ≥ 18 years
- ECOG performance status 0-1
- Albumin> 28 g/l, bilirubin < 50 µmol/l, INR < 2.3, AST/ALT < 5 times ULN, within 6 weeks prior to randomization
- Platelets will be preferably ≥ 50x10E9/ l (if not, thrombocytes transfusion is allowed to ensure a safe procedure at the discretion of the interventional radiologist and gastroenterologist). Leukocytes > 1.5x10E9/l, Hb > 6 mmol/l, within 6 weeks prior to randomization
- Written informed consent
- Willing and able to comply to the follow-up schedule
- Planned to start treatment within 6 weeks from randomization.
Who cannot join
- Eligibility for resection or RFA
- More than three tumors in the liver
- Ascites
- Any signs of acute viral or non-viral hepatitis
- Encephalopathy
- Vascular tumor invasion (contact with the vessel will not be considered contraindication).
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- Previous radiotherapy to the liver
- Known current pregnancy
- Distance from the tumor to the esophagus, stomach, duodenum, small bowel or large bowel < 0.5 cm on CT or on MRI (randomization imaging). Depending on the SBRT technique used, the minimum acceptable distance may vary and be larger for one technique compared to the other
- Uncontrolled portal hypertension (high bleeding risk). If gastroscopy has been performed, untreated esophageal varices grade III or IV.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
Netherlands8 sites
AMC
Amsterdam
VU MC
Amsterdam
LUMC
Leiden
Maastro
Maastricht
UMC Maastricht
Maastricht
UMC St Radboud
Nijmegen
Erasmus MC
Rotterdam, South Holland
UMC Utrecht
Utrecht
About this study
Official title: Transarterial Chemoembolization With Drug-Eluting Beads (Standard Arm) Versus Stereotactic Body Radiation Therapy (Experimental Arm) for Hepatocellular Carcinoma: A Multicenter Randomized Phase II Trial
Rationale:
This study will compare head to head in patients with hepatocellular carcinoma (HCC) ineligible for surgery or radiofrequency ablation, the standard treatment arm, transarterial chemoembolization with drug-eluting beads (TACE-DEB), with the experimental arm, stereotactic body radiation therapy (SBRT). The investigators hypothesis is that the time to progression is more favorable after SBRT than after TACE-DEB. The expected time to include the required patients for this trial will be four years.
Read more
To the best of the investigators knowledge this study will be the first in the world that will compare both techniques in a randomized trial.
Objective:
To assess the time to progression after TACE-DEB and after SBRT in a comparable population of patients diagnosed with HCC.
Study design:
Randomized, prospective, open-label, and phase II study.
Study population:
Patients diagnosed with HCC, Child-Pugh grade A, one to three tumors, cumulative diameter ≤ 6cm, and ≥ 18 years old.
Intervention:
Patients with HCC will be randomized to receive the standard treatment, TACE-DEB loaded with doxorubicin or the experimental arm, SBRT.
Main study parameters/endpoints:
The primary endpoint of this study will be time to progression, defined as time from randomization to radiological progression.
Secondary endpoints will be:
- Time to local recurrence
- Response rate (complete and partial response)
- Overall survival
- Toxicity
- Quality of life.
Read the detailed description
Primary liver cancer, particularly hepatocellular carcinoma (HCC) is a major health problem. Curative therapies for HCC are considered hepatic resection, liver transplantation and radiofrequency ablation (RFA). Hepatic resection is preferred for patients with limited disease, non-cirrhotic livers or selected patients with Child-Pugh A cirrhosis. Unlike resection, liver transplantation treats the tumor and the underlying cirrhosis present in the liver. Candidates for liver transplantation are preferably those with cirrhosis and tumors that comply with the Milan criteria (single tumor <5cm or 1-3 tumors each of ≤ 3cm). Because most patients are not amenable to resection or liver transplantation, RFA has emerged as an effective treatment option. RFA is limited by the location of the tumor in the liver and by the tumor size with best results after RFA achieved for tumors ≤3cm. For patients that are not eligible for RFA due to large or multifocal tumors, transarterial chemoembolization with drug-eluting beads (TACE-DEB) is the preferred treatment.
Stereotactic body radiation therapy (SBRT) delivers a highly effective dose of irradiation to the tumor while maximally avoiding dose delivery to surrounding healthy structures. SBRT is offered as an ablative local treatment with reported high percentages of complete and partial responses with limited toxicity.
An international expert committee on HCC has recommended time to progression (TTP) as primary endpoint for phase II randomized trials. Although data is scarce the best published median TTP after TACE-DEB was 16 months and after SBRT 36.5months in a more or less comparable patient population (Barcelona Clinic Liver Cancer stage system A-C).
The present study will include patients not eligible for resection or RFA. Patients may be eligible for bridging or for down staging to transplantation. Well compensated liver cirrhosis (Child-Pugh A) and disease confined to the liver (one to three tumors cumulative diameter ≤ 6cm) is required. To our knowledge this trial will be the first in the world to compare TACE-DEB and SBRT. This trial may have a big impact on the control of the disease and may contribute to change the standard of care from a palliative to a more radical/curative intention in this patient population
- Conditions
- Liver Neoplasms
- Being tested
- Radiation therapy, chemoembolization
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation therapyRadiation
6 fractions of 8-9Gy
chemoembolizationDevice
Up to 4 sessions
| Study group | Role | What they receive |
|---|---|---|
| Transarterial chemoembolization | Active comparator | Chemoembolization will be performed through a transarterial route delivering drug eluting beads, i.e. hydrogel-based microspheres (Biocompatibles UK, Ltd, HepaSphere Biosphere Medical) loaded with the chemotherapeutic agent doxorubicin. Receives: Device: chemoembolization |
| Stereotactic body radiation therapy | Experimental | Risk-adapted dose prescription for delivering the highest possible tumor dose not exceeding the maximum dose in 6 fractions of 8-9 Gy, while hepatic normal tissue complication probability (NTCP) < of 5% Receives: Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to progression
Measured: 4 years
Secondary outcomes (5)
Time to local recurrence
Measured: 4 years
Response rate
Measured: 4 years
Overall survival
Measured: 4 years
Toxicity
Common toxicity criteria v4.0
Measured: 4 years
Quality of life
EORTC Quality of life forms C-30 and HCC-18, Quality of life form Euro QoL5D
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2015 (estimated)
- Study start30 Apr 2015
- Primary completion30 Apr 2020
- Study completion30 Apr 2020
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver NeoplasmsStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe 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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society, UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), VU University of Amsterdam, Radboud University Medical Center, Maastricht University Medical Center, Maastro Clinic, The Netherlands, Leiden University Medical Center, Universitaire Ziekenhuizen KU Leuven, University Hospital, Antwerp, University Hospital, Lille
- Responsible party
- Principal investigator, Alejandra Mendez Romero, Erasmus Medical Center
- Investigators
- Alejandra Mendez Romero, MD PhD, Principal investigator, Erasmus Medical CenterAdriaan Moelker, MD PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02470533
- Sponsor's protocol ID
- NL51318.078.14
- Acronym
- TRENDY
- Status last verified
- Jan 2021
- First submitted
- 8 Jun 2015
- Last updated
- 27 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transarterial Chemoembolization With Drug-Eluting Beads (Standard Arm) Versus Stereotactic Body Radiation Therapy (Experimental Arm) for Hepatocellular Carcinoma: A Multicenter Randomized Phase II Trial
- ClinicalTrials.gov ID
- NCT02470533
- Acronym / sponsor ID
- TRENDY / NL51318.078.14
- Conditions
- Liver Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Dutch Cancer Society, UMC Utrecht, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), VU University of Amsterdam, Radboud University Medical Center, Maastricht University Medical Center, Maastro Clinic, The Netherlands, Leiden University Medical Center, Universitaire Ziekenhuizen KU Leuven, University Hospital, Antwerp, University Hospital, Lille
- Study start
- 30 Apr 2015 (actual)
- Primary completion
- 30 Apr 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 12 Jun 2015 (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.
Rationale:
This study will compare head to head in patients with hepatocellular carcinoma (HCC) ineligible for surgery or radiofrequency ablation, the standard treatment arm, transarterial chemoembolization with drug-eluting beads (TACE-DEB), with the experimental arm, stereotactic body radiation therapy (SBRT). The investigators hypothesis is that the time to progression is more favorable after SBRT than after TACE-DEB. The expected time to include the required patients for this trial will be four years.
To the best of the investigators knowledge this study will be the first in the world that will compare both techniques in a randomized trial.
Objective:
To assess the time to progression after TACE-DEB and after SBRT in a comparable population of patients diagnosed with HCC.
Study design:
Randomized, prospective, open-label, and phase II study.
Study population:
Patients diagnosed with HCC, Child-Pugh grade A, one to three tumors, cumulative diameter ≤ 6cm, and ≥ 18 years old.
Intervention:
Patients with HCC will be randomized to receive the standard treatment, TACE-DEB loaded with doxorubicin or the experimental arm, SBRT.
Main study parameters/endpoints:
The primary endpoint of this study will be time to progression, defined as time from randomization to radiological progression.
Secondary endpoints will be:
- Time to local recurrence
- Response rate (complete and partial response)
- Overall survival
- Toxicity
- Quality of life.
Detailed description
Primary liver cancer, particularly hepatocellular carcinoma (HCC) is a major health problem. Curative therapies for HCC are considered hepatic resection, liver transplantation and radiofrequency ablation (RFA). Hepatic resection is preferred for patients with limited disease, non-cirrhotic livers or selected patients with Child-Pugh A cirrhosis. Unlike resection, liver transplantation treats the tumor and the underlying cirrhosis present in the liver. Candidates for liver transplantation are preferably those with cirrhosis and tumors that comply with the Milan criteria (single tumor <5cm or 1-3 tumors each of ≤ 3cm). Because most patients are not amenable to resection or liver transplantation, RFA has emerged as an effective treatment option. RFA is limited by the location of the tumor in the liver and by the tumor size with best results after RFA achieved for tumors ≤3cm. For patients that are not eligible for RFA due to large or multifocal tumors, transarterial chemoembolization with drug-eluting beads (TACE-DEB) is the preferred treatment.
Stereotactic body radiation therapy (SBRT) delivers a highly effective dose of irradiation to the tumor while maximally avoiding dose delivery to surrounding healthy structures. SBRT is offered as an ablative local treatment with reported high percentages of complete and partial responses with limited toxicity.
An international expert committee on HCC has recommended time to progression (TTP) as primary endpoint for phase II randomized trials. Although data is scarce the best published median TTP after TACE-DEB was 16 months and after SBRT 36.5months in a more or less comparable patient population (Barcelona Clinic Liver Cancer stage system A-C).
The present study will include patients not eligible for resection or RFA. Patients may be eligible for bridging or for down staging to transplantation. Well compensated liver cirrhosis (Child-Pugh A) and disease confined to the liver (one to three tumors cumulative diameter ≤ 6cm) is required. To our knowledge this trial will be the first in the world to compare TACE-DEB and SBRT. This trial may have a big impact on the control of the disease and may contribute to change the standard of care from a palliative to a more radical/curative intention in this patient population
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transarterial chemoembolization | Active comparator | Device: chemoembolizationChemoembolization will be performed through a transarterial route delivering drug eluting beads, i.e. hydrogel-based microspheres (Biocompatibles UK, Ltd, HepaSphere Biosphere Medical) loaded with the chemotherapeutic agent doxorubicin. |
| Stereotactic body radiation therapy | Experimental | Radiation: Radiation therapyRisk-adapted dose prescription for delivering the highest possible tumor dose not exceeding the maximum dose in 6 fractions of 8-9 Gy, while hepatic normal tissue complication probability (NTCP) < of 5% |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients diagnosed with HCC Patients can be included if they require treatment prior to liver transplantation.
- Barcelona Clinic Liver Cancer Stage System class A-B
- One to three tumors of maximum cumulative diameter ≤ 6 cm measured in all 3 axes.
- Measurable disease to be selected as a target on CT/MRI-scan, according to mRECIST criteria for HCC within 6 weeks prior to randomization (≥ 1cm at least in one dimension, suitable for repeated measurement, and arterial enhancement) [44].
- Tumor visibility on CT
Key exclusion criteria (10 listed)
- Eligibility for resection or RFA
- More than three tumors in the liver
- Ascites
- Any signs of acute viral or non-viral hepatitis
- Encephalopathy
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 |
|---|---|---|
| Radiation therapy6 fractions of 8-9Gy | Radiation | Stereotactic body radiation therapy |
| chemoembolizationUp to 4 sessions | Device | Transarterial chemoembolization |
Primary outcome
Time to progression
Time frame: 4 years
5 secondary outcomes
Time to local recurrence
Time frame: 4 years
Response rate
Time frame: 4 years
Overall survival
Time frame: 4 years
Toxicity
Time frame: 4 years
Quality of life
Time frame: 4 years
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
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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.
Alejandra Mendez Romero, MD PhD principal investigator
Erasmus Medical Center
Adriaan Moelker, MD PhD principal investigator
Erasmus Medical Center
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiation therapy and chemoembolization in people with Liver Neoplasms, run by Erasmus Medical Center at 11 sites in 3 countries.
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 13 inclusion and 10 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 27 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Netherlands, Belgium, France. 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: Low accrual). 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 (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2021.