Clinical trial NCT04269499: Real-time Imaging of Holmium Radioembolization: a Feasibility Study
Official title: Real-time MR Imaged Treatment With Holmium Microspheres of Patients With Primary or Secondary Liver Cancer; a Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Cancer
Liver Metastases
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Quirem Medical B.V.
First posted: 2020-02-13
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-arm, interventional, feasibility
Primary purpose: TREATMENT

Brief summary: This is a feasibility study in which patients with liver tumors are treated with holmium radioembolization under real time MR imaging.


Eligibility criteria: Inclusion Criteria:

1. Patients must have given written informed consent.
2. Female or male aged 18 years and over.
3. Diagnosis of hepatocellular carcinoma or cholangiocarcinoma in the liver or diagnosis of metastatic malignancy to the liver (primary tumours: colorectal cancer, melanoma, breast cancer or neuro-endocrine tumour) with limited disease outside the liver (i.e. liver-dominant disease) defined as the sum of the diameters of all metastases in the liver be more than 200% of the sum of the diameters of all soft tissue lesions outside the liver.
4. Patient is not amenable for standard therapies (other than radioembolisation) or patient refuses standard therapies
5. Life expectancy of 12 weeks or longer.
6. World Health Organisation (WHO) Performance status 0-1 (see Appendix III).
7. One or more measurable lesions of at least 10 mm in the longest diameter by spiral CT according to the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.
8. Negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

1. Brain metastases or spinal cord compression, unless irradiated at least 4 weeks prior to the date of the experimental treatment and stable without steroid treatment for at least 1 week
2. Radiation therapy within the last 4 weeks before the start of study therapy.
3. The last dose of prior systemic therapy has been received less than 4 weeks prior the start of study therapy.
4. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy.
5. Any unresolved toxicity greater than National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE version 4.0, see Appendix II) grade 2 from previous anti-cancer therapy.
6. Serum bilirubin \> 1.5 x Upper Limit of Normal (ULN).
7. Glomerular filtration rate \<35 ml/min, determined according to the Modification of Diet in Renal Disease formula.
8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \> 5 x ULN.
9. Leukocytes \< 4.0 109/l and/or platelet count \< 60 109/l.
10. 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.
11. Pregnancy or breast feeding (women of child-bearing potential).
12. Patients suffering from diseases with an increased chance of liver toxicity, such as primary biliary cirrhosis or xeroderma pigmentosum.
13. Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression.
14. Patients ineligible to undergo MR imaging.
15. Patients who are claustrophobic.
16. Patient who had prior liver resection and/or coil placement inside the liver, expected to cause imaging artefacts on MRI that will limit MR quantification.
17. Patients who are declared incompetent.
18. Previous enrolment in the present study or previous treatment with radioembolisation.
19. Portal vein thrombosis (tumour 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.
20. 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.
21. Untreated active hepatitis.
22. Transjugular intrahepatic portosystemic shunt (TIPS).
23. Body weight over 150 kg (because of maximum table load).
24. Severe allergy for intravenous contrast agents used

    1. Iomeron®, because of CT evaluation, pre-treatment angiography and treatment angiography.
    2. Dotarem or Primovist, depending on the agent used at the time of treatment
25. Lung shunt \>30 Gy, as calculated using scout dose SPECT/CT.
26. Uncorrectable extrahepatic deposition of scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted.

Primary outcomes:
measure: Feasibility of MR imaged administration of holmium microspheres
timeFrame: 1 month after inclusion
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to 3 months after treatment
measure: Tumor/non-tumor ratio on MR based dosimetry
timeFrame: 1 month after inclusion
measure: Comparison of dosimetry in Gray between MR based and SPECT based dose maps
timeFrame: 1 month after inclusion
measure: Tumor response after 3 months based on CT imaging (according to RECIST 1.1 criteria)
timeFrame: 3 months after treatment
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
state: Gelderland
Study officials:
affiliation: Associate professor
name: Frank Nijsen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roosen J, Westlund Gotby LEL, Arntz MJ, Futterer JJ, Janssen MJR, Konijnenberg MW, van Wijk MWM, Overduin CG, Nijsen JFW. Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery. Eur J Nucl Med Mol Imaging. 2022 Nov;49(13):4705-4715. doi: 10.1007/s00259-022-05902-w. Epub 2022 Jul 13.