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

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Neoplasms
• Intervention / Treatment: Device: Holmium-166 polylactic microspheres

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584CX
    • Department of Radiology University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 1, 2012
• First Submitted That Met QC Criteria: June 1, 2012
• First Posted (Estimate): June 5, 2012

Study Record Updates

• Last Update Posted (Estimate): August 27, 2015
• Last Update Submitted That Met QC Criteria: August 26, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: liver tumors
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: UMCU-11-538