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

NCT03379844 | Completed Phase 2 DMC

• 1 other identifier: NL52338.041.17
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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 options.

Conditions

Hepatocellular Carcinoma; Hepatocellular Carcinoma Non-resectable

Outcome Measures

Primary Outcomes (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

  Up to 6 months

Secondary Outcomes (7)

• Tumor response based on radiologic assessment of MRI scans using mRECIST

  Up to 6 months

• Changes in tumor marker alpha-fetoprotein

  Up to 6 months

• Quality of Life (QoL) using EORTC C30

  Up to 6 months

• Quality of Life (QoL) using EORTC HCC18

  Up to 6 months

• Quality of Life (QoL) using BPI-SF

  Up to 6 months

Study Arms (1)

Holmium-166 radioembolization

EXPERIMENTAL

Device: Holmium-166 radioembolization

Interventions

Holmium-166 radioembolization DEVICE

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.

Holmium-166 radioembolization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• UMC Utrecht: lead
• Dutch Cancer Society: collaborator
• Erasmus Medical Center: collaborator
• Quirem Medical B.V.: collaborator

Study Sites (2)

Erasmus Medical Center

Rotterdam, 3015CN, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 39786516 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Marnix G. Lam, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: November 21, 2017
• First Posted: December 20, 2017
• Study Start: August 21, 2017
• Primary Completion: January 1, 2020
• Study Completion: August 1, 2021
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)