Hepatocellular Carcinoma Non-resectableiHEPARNCT05114148
Individualized Dosimetry for Holmium-166-radioembolization in Patients With Unresectable Hepatocellular Carcinoma
A study testing Holmium-166 radioembolization in people with Hepatocellular Carcinoma Non-resectable, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
Patients with hepatocellular carcinoma often die from intrahepatic disease because current treatment options are limited. Local treatment using 166Ho-radioembolization (166Ho-RE) offers a safe and effective treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma Non-resectable
- What is being tested?
- Holmium-166 radioembolization
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2022to 1 Nov 2025
- Phase
- Interventional
- 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
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Patients must have given written informed consent.
- Female or male aged 18 years and over.
- Diagnosis of HCC established according to the Netherlands HCC guideline criteria (in line with American AASLD criteria): nodule >1 cm in a patient at risk for HCC, with combination of arterial hypervascularity and venous or delayed phase wash-out on multiphase CT-scan or MRI-scan.2, 4 LR-5 and LR- 4 based on Liver Imaging Reporting and Data System can be included based on discretion of the principal investigator.
- No curative treatment options (resection, transplant, or in case of solitary tumor <5 cm, RFA).
- Life expectancy of at least 6 months.
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- ECOG Performance status 0-1 (Table 2).
- Liver-dominant disease (maximum 5 lung nodules all ≤1.0 cm, solitary clinically stable adrenal metastasis, and mesenteric or portal lymph nodes all ≤2.0 cm are accepted).
- Child-Pugh class A5-6 or B7.
- At least one measurable liver lesion according to the modified RECIST criteria.(26)
- Negative pregnancy test for women of childbearing potential. Female patients of childbearing potential should use a highly effective acceptable method of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation) or should be more than 1 year postmenopausal or surgically sterile during their participation in this study (from the time they sign the consent form), to prevent pregnancy.
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Evidence of significant extrahepatic disease (MRI-scan liver and multiphase abdominal CT as well as a thoracic CT are routinely performed at screening).
- Hepatic radiation therapy within the last 4 weeks before the start of study therapy.
- Previous or current treatment with RE. Previous treatment with TACE, surgery, RFA, and previous or current treatment with sorafenib are allowed.
- Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
- Serum bilirubin >34.2 micromole/L (2 mg/dL).
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- Glomerular filtration rate <35 ml/min.
- Non-correctable INR >1.5 in case of femoral approach (as opposed to radial).
- Leukocytes <2 109/l and/or platelet count <50 109/l.
- Significant cardiac event (e.g. myocardial infarction, superior vena cava (SVC) syndrome, New York Heart Association (NYHA) classification of heart disease ≥2) within 3 months before entry, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia.
- Pregnancy or breastfeeding.
- Patients suffering from psychic disorders that make a comprehensive judgment impossible, such as psychosis, hallucinations and/or depression.
- Patients who are declared incapacitated.
- Previous enrollment in the present study.
- Male patients who are not surgically sterile or do not use an acceptable method of contraception during their participation in this study (from the time they sign the consent form), to prevent pregnancy in a partner.
- Evidence of untreated, clinically significant grade 3 portal hypertension (i.e. large varices at oesophago-gastro-duodenoscopy). In these cases, therapy with non-selective beta-blocker (propranolol) or rubber band ligation should be instituted according to accepted guidelines. In case of small varices, prophylactic propranolol is advised.
- Portal vein thrombosis (tumor and/or bland) of the main branch (diagnosed on contrast enhanced transaxial images). Involvement of the right or left portal vein branches and more distal is accepted.
- Untreated active hepatitis. In case of detectable viral HBV load, appropriate treatment should be instituted.
- Transjugular intrahepatic portosystemic shunt (TIPS).
- Body weight over 150 kg (because of maximum table load).
- Severe allergy for intravenous contrast used (Visipaque®)(because of CT evaluation, pre-treatment angiography and treatment angiography).
- Lung shunt >30 Gy, as calculated using scout dose SPECT/CT. Uncorrectable extrahepatic deposition of scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
UMC Utrecht
Utrecht, 3584 CX
Tjitske Kent - Bosma, 0031-88-7551321, tbosma@umcutrecht.nl
Joep de Bruijne, MD, PhD
About this study
Official title: Individualized Dosimetry for Holmium-166-radioembolization in Patients With Unresectable Hepatocellular Carcinoma; a Multi-center, Interventional, Non-randomized, Non-comparative, Open Label, Early Phase II Study
Patients with hepatocellular carcinoma often die from intrahepatic disease because current treatment options are limited. Local treatment using 166Ho-radioembolization (166Ho-RE) offers a safe and effective treatment. Because 166Ho-microspheres are used as a scout dose for treatment simulaton and for the actual treatment itself, a tailored approach can be used. This concept has proven to be more predictive than the 90Y-radioembolization concept (current standard-of-care), which is a based on a surrogate scout dose (i.e. 99mTc-MAA). A personal treatment plan may be used for 166Ho-radioembolization to optimize efficacy, based on scout dose distribution. However, individualized treatment planning inherently leads to treatment doses that deviate from the currently approved 'one-size-fits-all' approach (i.e. 60 Gy average absorbed dose for all patients). Therefore, safety of individualized 166Ho-RE will be evaluated first to validate safety and confirm safety thresholds. These thresholds will be used in subsequent randomized controlled studies.
Read the detailed description
The presented study proposal is a sequel study after a successful completion of the HEPAR Primary study (all patients were treated, last follow-up visit planned for August 2020). In the HEPAR Primary study, all treatments were planned using one compartment modeling, which included the target volume without distinction between tumor and non-tumor compartments. Each patient was treated with an average absorbed dose of 60 Gy in the target volume. In some patients this treatment approach resulted in a high tumor and low normal liver absorbed dose, in others this resulted in the opposite. No distinction was made because thresholds for a safe normal liver and effective tumor absorbed dose were not known, since HEPAR Primary was the first clinical study on 166Ho-RE in HCC. The study confirmed safety of a 60 Gy average absorbed dose and gave insights in the previously unknown thresholds for a safe normal liver and effective tumor absorbed dose.
The primary hypothesis of the iHEPAR study is that dosimetry-based individualized treatment planning is at least as safe as standard of care one compartment treatment planning, used in HEPAR Primary, but with the potential of improved treatment outcomes. One compartment modeling has the inherent risk of under- or over-dosing. Dosimetry-based individualized treatment planning aims for an effective tumor absorbed dose, while keeping the non-tumor absorbed dose within safety limits. So far, only one compartment modeling was established as a safe and effective treatment approach in 166Ho-RE. This phase II study aims to evaluate the safety and efficacy of dosimetry-based individualized 166Ho-RE in HCC. This data will be used for the design of future randomized controlled trials.
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Being tested
- Holmium-166 radioembolization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Holmium-166 radioembolizationDevice
Individualized 166Ho-RE will be performed via a catheter during angiography. Dosimetry-based treatment planning will be individualized based on Q-Suite™ software.
| Study group | Role | What they receive |
|---|---|---|
| Holmium-166 radioembolization | Experimental | Individualized holmium-166 radioembolization will be performed via a catheter during angiography. Dosimetry-based treatment planning will be individualized based on Q-Suite™ software. Receives: Device: Holmium-166 radioembolization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of unacceptable toxicity.
For this study, unacceptable toxicity is defined as the occurrence of RE-induced liver disease, defined as a total bilirubin increase grade 3 or higher according to the CTCAE version 4.03, in combination with ascites and low albumin, in the absence of disease progression. Any (suspected unexpected) serious adverse event of (suspected unexpected) serious device effect that is possibly, probably or definitely related to study treatment will also be regarded unacceptable toxicity.
Measured: 6 months
Secondary outcomes (8)
Rate of respons
Efficacy as a secondary endpoint will be based on the modified RECIST (mRECIST) response evaluation criteria.
Measured: 6 months
Anti-tumor effect (alfa-fetoprotein).
Tumor marker changes will be expressed as a percentage of the pre-treatment values.
Measured: 6 months
The correlation between tumor absorbed dose in Gy and rate of response according to modified RECIST.
Response will be measured according to modified RECIST.
Measured: 6 months
The correlation between non-tumor liver absorbed dose in Gy and rate of unacceptable toxicity.
For this study, unacceptable toxicity is defined as the occurrence of RE-induced liver disease, defined as a total bilirubin increase grade 3 or higher according to the CTCAE version 4.03, in combination with ascites and low albumin, in the absence of disease progression. Any (suspected unexpected) serious adverse event of (suspected unexpected) serious device effect that is possibly, probably or definitely related to study treatment will also be regarded unacceptable toxicity.
Measured: 6 months
EORTC Quality of Life questionnaire number C30
The questionnaire specific manual will be used for assessment and analysis.
Measured: 6 months
EORTC Quality of Life questionnaire number HCC18
The questionnaire specific manual will be used for assessment and analysis.
Measured: 6 months
Brief Pain Inventory questionnaire number BPI-SF
The questionnaire specific manual will be used for assessment and analysis.
Measured: 6 months
Assessment of regional liver function
To evaluate overall and regional liver function as measured by hepatobiliary scintigraphy using 99mTc-mebrofenin SPECT/CT, pre- and post-radioembolization.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2021
- Study start1 Mar 2022
- Primary completion1 Nov 2024 (estimated)
- Study completion1 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma Non-resectableStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Multi-center, interventional, treatment, non-randomized, open label, non-comparative, early clinical safety study. The study is a collaboration between UMC Utrecht and Erasmus MC Rotterdam.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, Terumo Corporation
- Responsible party
- Principal investigator, Marnix Lam, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05114148
- Sponsor's protocol ID
- NL74751.041.21
- Acronym
- iHEPAR
- Status last verified
- Nov 2022
- First submitted
- 1 Oct 2021
- Last updated
- 10 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualized Dosimetry for Holmium-166-radioembolization in Patients With Unresectable Hepatocellular Carcinoma; a Multi-center, Interventional, Non-randomized, Non-comparative, Open Label, Early Phase II Study
- ClinicalTrials.gov ID
- NCT05114148
- Acronym / sponsor ID
- iHEPAR / NL74751.041.21
- Conditions
- Hepatocellular Carcinoma Non-resectable
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, Terumo Corporation
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 1 Nov 2024 (estimated)
- Study completion
- 1 Nov 2025 (estimated)
- First posted
- 9 Nov 2021 (actual)
- 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.
Patients with hepatocellular carcinoma often die from intrahepatic disease because current treatment options are limited. Local treatment using 166Ho-radioembolization (166Ho-RE) offers a safe and effective treatment. Because 166Ho-microspheres are used as a scout dose for treatment simulaton and for the actual treatment itself, a tailored approach can be used. This concept has proven to be more predictive than the 90Y-radioembolization concept (current standard-of-care), which is a based on a surrogate scout dose (i.e. 99mTc-MAA). A personal treatment plan may be used for 166Ho-radioembolization to optimize efficacy, based on scout dose distribution. However, individualized treatment planning inherently leads to treatment doses that deviate from the currently approved 'one-size-fits-all' approach (i.e. 60 Gy average absorbed dose for all patients). Therefore, safety of individualized 166Ho-RE will be evaluated first to validate safety and confirm safety thresholds. These thresholds will be used in subsequent randomized controlled studies.
Detailed description
The presented study proposal is a sequel study after a successful completion of the HEPAR Primary study (all patients were treated, last follow-up visit planned for August 2020). In the HEPAR Primary study, all treatments were planned using one compartment modeling, which included the target volume without distinction between tumor and non-tumor compartments. Each patient was treated with an average absorbed dose of 60 Gy in the target volume. In some patients this treatment approach resulted in a high tumor and low normal liver absorbed dose, in others this resulted in the opposite. No distinction was made because thresholds for a safe normal liver and effective tumor absorbed dose were not known, since HEPAR Primary was the first clinical study on 166Ho-RE in HCC. The study confirmed safety of a 60 Gy average absorbed dose and gave insights in the previously unknown thresholds for a safe normal liver and effective tumor absorbed dose.
The primary hypothesis of the iHEPAR study is that dosimetry-based individualized treatment planning is at least as safe as standard of care one compartment treatment planning, used in HEPAR Primary, but with the potential of improved treatment outcomes. One compartment modeling has the inherent risk of under- or over-dosing. Dosimetry-based individualized treatment planning aims for an effective tumor absorbed dose, while keeping the non-tumor absorbed dose within safety limits. So far, only one compartment modeling was established as a safe and effective treatment approach in 166Ho-RE. This phase II study aims to evaluate the safety and efficacy of dosimetry-based individualized 166Ho-RE in HCC. This data will be used for the design of future randomized controlled trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Multi-center, interventional, treatment, non-randomized, open label, non-comparative, early clinical safety study. The study is a collaboration between UMC Utrecht and Erasmus MC Rotterdam.
| Arm | Type | Receives |
|---|---|---|
| Holmium-166 radioembolization | Experimental | Device: Holmium-166 radioembolizationIndividualized holmium-166 radioembolization will be performed via a catheter during angiography. Dosimetry-based treatment planning will be individualized based on Q-Suite™ software. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Patients must have given written informed consent.
- Female or male aged 18 years and over.
- Diagnosis of HCC established according to the Netherlands HCC guideline criteria (in line with American AASLD criteria): nodule >1 cm in a patient at risk for HCC, with combination of arterial hypervascularity and venous or delayed phase wash-out on multiphase CT-scan or MRI-scan.2, 4 LR-5 and LR- 4 based on Liver Imaging Reporting and Data System can be included based on discretion of the principal investigator.
- No curative treatment options (resection, transplant, or in case of solitary tumor <5 cm, RFA).
Key exclusion criteria (22 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Evidence of significant extrahepatic disease (MRI-scan liver and multiphase abdominal CT as well as a thoracic CT are routinely performed at screening).
- Hepatic radiation therapy within the last 4 weeks before the start of study therapy.
- Previous or current treatment with RE. Previous treatment with TACE, surgery, RFA, and previous or current treatment with sorafenib are allowed.
- Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
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 |
|---|---|---|
| Holmium-166 radioembolizationIndividualized 166Ho-RE will be performed via a catheter during angiography. Dosimetry-based treatment planning will be individualized based on Q-Suite™ software. | Device | Holmium-166 radioembolization |
Primary outcome
Rate of unacceptable toxicity.
Time frame: 6 months
For this study, unacceptable toxicity is defined as the occurrence of RE-induced liver disease, defined as a total bilirubin increase grade 3 or higher according to the CTCAE version 4.03, in combination with ascites and low albumin, in the absence of disease progression. Any (suspected unexpected) serious adverse event of (suspected unexpected) serious device effect that is possibly, probably or definitely related to study treatment will also be regarded unacceptable toxicity.
8 secondary outcomes
Rate of respons
Time frame: 6 months
Anti-tumor effect (alfa-fetoprotein).
Time frame: 6 months
The correlation between tumor absorbed dose in Gy and rate of response according to modified RECIST.
Time frame: 6 months
The correlation between non-tumor liver absorbed dose in Gy and rate of unacceptable toxicity.
Time frame: 6 months
EORTC Quality of Life questionnaire number C30
Time frame: 6 months
EORTC Quality of Life questionnaire number HCC18
Time frame: 6 months
Brief Pain Inventory questionnaire number BPI-SF
Time frame: 6 months
Assessment of regional liver function
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2022.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Holmium-166 radioembolization in people with Hepatocellular Carcinoma Non-resectable, run by UMC Utrecht at 1 site in Netherlands.
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 11 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 10 Nov 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 Netherlands. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of unacceptable toxicity. (time frame: 6 months). 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 10 Nov 2022.