Radioactive Holmium Microspheres for the Treatment of Unresectable Liver Metastases

Study Overview
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Brief Summary
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Radioembolisation is a known method for the treatment of liver tumors and or livermetastases. Currently small beadlets called microspheres are used that are loaded with the beta radiation emitting Yttrium-90. Holmium-166 microspheres have different physical characteristics including good visualisation in gammacameras due to the gamma emission. Because of the higher specific activity higher radiation doses to the liver will be used compared to the standard Yttrium treatment. It is hypothesized that higher doses of irradiation have an improved antitumor effect.

Official Title
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Radioactive Holmium Microspheres for the Treatment of Patients With Unresectable Liver Metastases; a Single Center, Interventional, Non-randomized, Phase II (HEPAR II) Trial

Conditions
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Liver Neoplasms

Intervention / Treatment
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* Device: Holmium-166 polylactic microspheres


Participation Criteria
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Eligibility Criteria
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List of inclusion criteria: 1. Patients must have given written informed consent. 2. Female or male aged 18 years and over. 3. Diagnosis of metastatic malignancy to the liver and no detectable malignant disease outside the liver or diagnosis of metastatic malignancy to the liver with limited disease outside the liver (i.e. liver-dominant disease) defined as the sum of the diameters of all metastases in the liver to 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 for reasons of toxicity 5. Life expectancy of 12 weeks or longer. 6. World Health Organisation (WHO) Performance status 0-2 (see Appendix III). List of exclusion criteria: 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. Radiation therapy within the last 4 weeks before the start of study therapy. The last dose of prior chemotherapy has been received less than 4 weeks prior the start of study therapy. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy. 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. Serum bilirubin > 1.5 x Upper Limit of Normal (ULN). Glomerular filtration rate <35 ml/min, determined according to the Modification of Diet in Renal Disease formula. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) > 5 x ULN. Leukocytes < 4.0 109/l and/or platelet count < 150 109/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 breast feeding (women of child-bearing potential). Patients suffering from diseases with a increased chance of liver toxicity, such as primary biliary cirrhosis or xeroderma pigmentosum. Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression. Patients who are declared incompetent. Previous enrolment in the present study or previous treatment with radioembolisation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Holmium-166 MS radioembolization<br>Single radioembolization met Holmium-166 polylactic microspheres administered | Device: Holmium-166 polylactic microspheres<br>* Radioembolisation with 600 mg of Holmium-166 microspheres with a patient liver size adjusted activity. The desired whole liver dose is 60 Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target lesions tumour response | After the administration of the Ho-166 microspheres the size of the target lesions in the liver will be determined using RECIST 1.1 criteria using CT scan | 3 month after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity according CTC v 4 criteria | Clinical evaluation and laboratory testing after week 1,3,6,9,12,24,36,52 | Clinical evaluation after 1,3,6,9,12,24,36,52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver tumors