Radioactive Holmium Microspheres for the Treatment of Unresectable Liver Metastases (HEPAR-2)

• ClinicalTrials.gov Identifier: NCT01612325
• Recruitment Status: Completed
• First Posted: June 5, 2012
• Last Update Posted: August 27, 2015
• Sponsor: UMC Utrecht
• Information provided by (Responsible Party): B.A. Zonnenberg, UMC Utrecht

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Liver Neoplasms	Device: Holmium-166 polylactic microspheres	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Radioactive Holmium Microspheres for the Treatment of Patients With Unresectable Liver Metastases; a Single Center, Interventional, Non-randomized, Phase II (HEPAR II) Trial
• Study Start Date: May 2012
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Holmium-166 MS radioembolization; Single radioembolization met Holmium-166 polylactic microspheres administered	Device: Holmium-166 polylactic microspheres; Radioembolisation with 600 mg of Holmium-166 microspheres with a patient liver size adjusted activity. The desired whole liver dose is 60 Gy.

Outcome Measures

Primary Outcome Measures :

1. Target lesions tumour response [ Time Frame: 3 month after treatment ]
   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

Secondary Outcome Measures :

1. Toxicity according CTC v 4 criteria [ Time Frame: Clinical evaluation after 1,3,6,9,12,24,36,52 weeks ]
   Clinical evaluation and laboratory testing after week 1,3,6,9,12,24,36,52

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

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 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 who are declared incompetent.
15. Previous enrolment in the present study or previous treatment with radioembolisation.

Contacts and Locations

Locations

Netherlands

Department of Radiology University Medical Center Utrecht

Utrecht, Netherlands, 3584CX

Sponsors and Collaborators

UMC Utrecht

Investigators

• Principal Investigator: Bernard Zonnenberg, MD, PhD; UMCU Utrecht Netherlands
• Study Director: Martin Hendriks, MD, PhD; UMCU Utrecht, Netherlands

More Information

Publications:

Smits ML, Nijsen JF, van den Bosch MA, Lam MG, Vente MA, Huijbregts JE, van het Schip AD, Elschot M, Bult W, de Jong HW, Meulenhoff PC, Zonnenberg BA. Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial. J Exp Clin Cancer Res. 2010 Jun 15;29(1):70. doi: 10.1186/1756-9966-29-70.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Elschot M, Nijsen JF, Lam MG, Smits ML, Prince JF, Viergever MA, van den Bosch MA, Zonnenberg BA, de Jong HW. ((9)(9)m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with (1)(6)(6)Ho-microspheres. Eur J Nucl Med Mol Imaging. 2014 Oct;41(10):1965-75. doi: 10.1007/s00259-014-2784-9. Epub 2014 May 13.

• Responsible Party: B.A. Zonnenberg, principal investigator, UMC Utrecht
• ClinicalTrials.gov Identifier: NCT01612325
• Other Study ID Numbers: UMCU-11-538
• First Posted: June 5, 2012
• Last Update Posted: August 27, 2015
• Last Verified: August 2015

Keywords provided by B.A. Zonnenberg, UMC Utrecht:

liver tumors

Additional relevant MeSH terms:

Liver Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases