Radioactive holmium microspheres for the treatment of patients with unresectable liver metastases; a single center, interventional, non-randomized, phase II efficacy (HEPAR II) trial.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 48

Inclusion Criteria

* Patients must have given written informed consent.
* Female or male aged 18 years and over.
* 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 tbe more than 200% of the sum of the diameters of all soft tissue lesions outside the liver.
* Patiënt is not amenable for standard therapies or patient refuses standard therapies for reasons of toxicity
* Life expectancy of 12 weeks or longer.
* World Health Organisation (WHO) Performance status 0-2 .
* One or more measurable lesions at least 10 mm in the longest diameter by spiral CT according to the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.
* 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 chemotherapy 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 < 150 109/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 a increased chance of liver toxicity, such as primary biliairy 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 who are declared incompetent.
15. Previous enrolment in the present study or previous treatment with radioembolization.
16. Treated with an investigational agent within 42 days prior to starting study treatment.
17. Female patients who are not using an acceptable method of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation) OR are less than 1 year postmenopausal or surgically sterile during their participation in this study (from the time they sign the consent form) to prevent pregnancy.
18. 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.
19. Patients with abnormalities of the bile ducts (such as stents) with an increased chance of infections of the bile ducts. Or evidence of extensive portal hypertension, splenomegaly, ascites or active hepatitis (B and/or C).
20. Body weight over 150 kg.
21. Moderate or severe adverse reaction to i.v. contrast (Visipaque®), as defined by the ACR Manual on Contrast Media - Version 9 (2013) (see Appendix XIV).
22. MRI contra-indications: severe claustrophobia, metal shrapnel, implanted pacemaker and/or neurostimulators.
23. Liver tumour involvement >=70% as quantified on CT

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Target lesions tumour response at three months follow-up. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Overall tumour response.<br /><br>* Liver specific progression-free survival post 166Ho-RE.<br /><br>* Non-liver specific progression-free survival.<br /><br>* Overall survival.<br /><br>* Toxicity.<br /><br>* Quality of life.<br /><br>* Performance status.<br /><br>* Tc-99m-MAA and 166Ho-PLLA-MS scout and therapy dose SPECTs comparison.<br /><br>* Ho-166-PLLA-MS scout dose and total dose MRI comparison.<br /><br>* Ho-166-PLLA-MS scout dose and total dose PET/CT comparison.</p><br>