Holmium-166-radioembolization in NET After Lutetium-177-dotatate; an Efficacy Study (HEPAR_Plus)

This is an interventional treatment trial for Neuroendocrine Tumors focused on measuring Radioembolization, Somatostatin receptor treatment, Neuroendocrine tumors, Liver metastases Read More

Inclusion Criteria:

1. Patients must have given written informed consent.
2. Female or male aged 18 years and over.
3. Confirmed histological diagnosis NET, including bronchial carcinoids, and metastatic malignancy with liver metastases without standard therapeutic options for treatment including chemotherapy or surgery.
4. Patients must have been treated with 4 cycles of 200 mCi 177Lu-dotatate, the last cycle within 8-12 weeks of 166Ho-RE.
5. Life expectancy of 12 weeks or longer.
6. World Health Organisation (WHO) Performance status 0-2.
7. Liver disease with three or more measurable liver lesions according to the 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 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 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 < 3.0 x 109/l and/or platelet count < 100 x 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 nursing (women of child-bearing potential).
12. Patients suffering from diseases with an increased chance of liver toxicity.
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 RE.
16. 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.
17. 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.
18. Patients with abnormalities of the bile ducts (such as stents) with an increased chance of infections of the bile ducts (papillotomy and cholecystectomy are allowed). Or evidence of extensive portal hypertension, splenomegaly, ascites or active hepatitis (B and/or C).
19. Body weight over 150 kg.
20. Severe allergy for i.v. contrast (Visipaque®), used for CT evaluation, pre-treatment angiography and treatment angiography.
21. Liver tumour involvement ≥70% as quantified on CT.