Radioactive Holmium Microspheres for the Treatment of Liver Metastases

Radioactive Holmium Microspheres for the Treatment of Patients With Non-resectable Liver Metastases of Mixed Origin; a Single Center, Interventional, Non-randomized, Open Label, Safety Study.

The HEPAR study is aimed at determining the safety of radioactive holmium containing microspheres for the treatment of tumors in the liver. These microspheres will be administered by infusion in the liver artery using a arterial catheter in the femoral artery.

Inclusion Criteria:

Patients meeting the following criteria may enter the study:

1. Patients must have given written informed consent.
2. Female or male aged 18 years and over.
3. Confirmed histological diagnosis of metastatic malignancy with dominant liver metastases without standard therapeutic options for treatment including chemotherapy or surgery. Dominant liver metastases are defined (according to the Response Evaluation Criteria in Solid Tumors (RECIST) methodology, see Appendix IV) as the diameter of all metastases in the liver must be more than 200% of the sum of the diameters of all soft tissue lesions outside the liver.
4. Life expectancy of 12 weeks or longer.
5. World Health Organisation (WHO) Performance status 0-2 (see Appendix III).
6. One or more measurable lesions at least 10 mm in the longest diameter by spiral Computed Tomography (CT) scan (5 mm slice thickness) according to the RECIST criteria.
7. Negative pregnancy test for women of childbearing potential. -

Exclusion Criteria:

Patients meeting any of the following criteria cannot enter the study:

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 3.0, see Appendix II) grade 2 from previous anti-cancer therapy.

6. Serum bilirubin > 1.5 x Upper Limit of Normal (ULN).

7. Serum creatinine > 185 µmol/L.

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. Comorbidity with a grave prognosis (estimated survival <3 months) and/or worse then the basic disease for which the patients will be included in the study.

13. Patients with abnormalities of the bile ducts (such as stents) with a increased chance of infections of the bile ducts.

14. Patients suffering from diseases with a increased chance of liver toxicity, such as primary biliary cirrhosis or xeroderma pigmentosum.

15. Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression.

16. Patients who are declared incompetent.

17. Previous enrolment in the present study or previous treatment with radio-embolisation.

18. Treated with an investigational agent within 42 days prior to starting study treatment.

19. 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.

20. 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.

21. Evidence of portal hypertension, splenomegaly or ascites.

22. Body weight over 150 kg.

23. Active hepatitis (B and/or C).

24. Liver weight > 3 kg (determined by software using CT data).

25. Allergy for i.v. contrast used (Visipaque®).

26. MRI contra-indications: severe claustrophobia, metal shrapnel, implanted pacemaker and/or neurostimulators.

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