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Hepatocellular CarcinomaPhase 2NCT03379844

HEPAR Primary: Holmium-166-radioembolization in Hepatocellular Carcinoma Patients

A Phase 2 study testing Holmium-166 radioembolization in people with Hepatocellular Carcinoma and Hepatocellular Carcinoma Non-resectable, run by UMC Utrecht at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients with hepatocellular carcinoma often die from intrahepatic disease since current treatment options are generally limited. Local treatment using holmium radioembolization could offer an effective treatment and a more personal approach than yttrium radioembolization (standard-of-care) as holmium has more imaging… Read more about this study

Who is it for?
Ages 18 years and older
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
2 sitesNetherlands
Study dates
21 Aug 2017to 1 Aug 2021
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 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.I
  • No curative treatment options (resection, transplant, or in case of solitary tumor <5 cm, RFA).
  • Life expectancy of at least 6 months.
  • ECOG Performance status 0-1 (Table 2).
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  • Liver-dominant disease (maximum 5 lung nodules all ≤1.0 cm 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.21
  • Negative pregnancy test for women of childbearing potential. Female patients of child-bearing potential should use an 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

  • Evidence of significant extrahepatic disease (MRI-scan liver and multiphase abdominal CT as well as a thoracic CT are routinely performed at screening).
  • 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).
  • Glomerular filtration rate <35 ml/min, determined according to the Modification of Diet in Renal Disease formula.
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  • 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, treatment with a nucleos(t)ide analog such as entecavir or tenofovir 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

2 sites in 1 country.

Netherlands2 sites

  • Erasmus Medical Center

    Rotterdam, 3015CN

  • University Medical Center Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

About this study

Official title: Holmium-166-radioembolization in Patients With Unresectable Hepatocellular Carcinoma (HCC); a Multi-center, Interventional, Non-randomized, Non-comparative, Open Label, Early Phase II Study: HEPAR Primary

Patients with hepatocellular carcinoma often die from intrahepatic disease since current treatment options are generally limited. Local treatment using holmium radioembolization could offer an effective treatment and a more personal approach than yttrium radioembolization (standard-of-care) as holmium has more imaging options.

Read the detailed description

Primary objective:

  • To establish the safety and toxicity profile of holmium radioembolization in patients with hepatocellular carcinoma.

Secondary objectives:

  • To evaluate efficacy of holmium radioembolization in hepatocellular carcinoma without curative treatment options in a non-comparative phase II study.
  • To evaluate tumor marker response.
  • To evaluate Quality of Life (QoL).
  • To evaluate biodistribution / dosimetry.
  • To evaluate hepatic function.

Study design: Multi-center, interventional, treatment, non-randomized, open label, non-comparative, early phase II study. The study is a collaboration between UMC Utrecht and Erasmus MC Rotterdam. Recruitment and treatment of patients will take place in both centers.

Intervention: Holmium radioembolization will be performed via a catheter during angiography.

Being tested
Holmium-166 radioembolization
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Holmium-166 radioembolizationDevice

    An intra-arterial radioembolization procedure will be performed. The hepatic artery catheter is inserted via the femoral or radial artery under x-ray guidance by a trained interventional radiologist. The radiologist must repeatedly check the position of the catheter during the procedure to ensure it remains correctly sited and that reflux of the QuiremSpheres® into other organs does not occur. This is performed by injecting contrast medium. At the conclusion of the procedure, the catheter is removed.

Study groups in NCT03379844
Study groupRoleWhat they receive
Holmium-166 radioembolizationExperimentalNot described
Receives: Device: Holmium-166 radioembolization

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety, expressed as the rate of unacceptable toxicity.

    Safety, expressed as the rate of unacceptable toxicity, which is 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

    Measured: Up to 6 months

Secondary outcomes (7)

  1. Tumor response based on radiologic assessment of MRI scans using mRECIST

    Tumor response based on radiologic assessment of MRI scans using mRECIST

    Measured: Up to 6 months

  2. Changes in tumor marker alpha-fetoprotein

    Changes in tumor marker alpha-fetoprotein

    Measured: Up to 6 months

  3. Quality of Life (QoL) using EORTC C30

    Quality of Life (QoL) using EORTC C30

    Measured: Up to 6 months

  4. Quality of Life (QoL) using EORTC HCC18

    Quality of Life (QoL) using EORTC HCC18

    Measured: Up to 6 months

  5. Quality of Life (QoL) using BPI-SF

    Quality of Life (QoL) using BPI-SF

    Measured: Up to 6 months

  6. Biodistribution/dosimetry based on quantitative assessment of MRI scans

    Biodistribution/dosimetry based on quantitative assessment of MRI scans

    Measured: Up to 6 months

  7. Changes in hepatic function as determined by hepatobiliary scintigraphy

    Changes in hepatic function as determined by hepatobiliary scintigraphy

    Measured: Up to 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2017
  2. Study start21 Aug 2017
  3. Primary completion1 Jan 2020
  4. Study completion1 Aug 2021

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03379844
Sponsor's protocol ID
NL52338.041.17
Status last verified
Nov 2022
First submitted
21 Nov 2017
Last updated
8 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Reinders MTM, Smits MJL, van Erpecum K, de Bruijne J, Bruijnen RCG, Sprengers D, de Man R, Vegt E, IJzermans JNM, Lam MGEH, Braat AJAT. Hepatobiliary scintigraphy and liver function changes in patients with hepatocellular carcinoma treated with 166Ho-radioembolization : HBS in HCC treated with holmium-166. EJNMMI Res. 2025 Jan 9;15(1):2. doi: 10.1186/s13550-025-01196-9.

    PubMed 39786516

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Holmium-166 radioembolization in people with Hepatocellular Carcinoma and Hepatocellular Carcinoma Non-resectable, run by UMC Utrecht at 2 sites 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 10 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: finished, as of the sponsor's last update on 8 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 2 sites 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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety, expressed as the rate of unacceptable toxicity. (time frame: Up to 6 months). 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 NCT03379844, which also lists 1 linked publication.

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 8 Nov 2022.

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