Radioactive Holmium Microspheres for the Treatment of Liver Metastases

NCT01031784 | Completed Phase 1 DMC

• 1 other identifier: 08-450
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Liver Metastasis; Liver Tumors

Keywords

liver metastasis; Liver tumors; microspheres; holmium; toxicity

Outcome Measures

Primary Outcomes (1)

• Toxicity of Ho-166 poly lactic microspheres using CTC vs 3 criteria

  12 weeks

Secondary Outcomes (1)

• tumor response according to RECIST criteria

  12 weeks

Study Arms (1)

Holmium-166 microspheres, intra-arterial

EXPERIMENTAL

intra-arterial administration of holmium-166 microspheres in the liver

Device: holmium-166 poly lactic acid microspheres; Device: holmium 166 microspheres

Interventions

holmium-166 poly lactic acid microspheres DEVICE

Intra arterial administration of radioactive Holmium 166 microspheres; 600 mg with a specific activity ranging from 1260 MBq per kilo liver weight to 5040 MBq in the highest dose

Holmium-166 microspheres, intra-arterial

holmium 166 microspheres DEVICE

intra arterial administration of holmium 166 microsphers in the hepatic artery

Holmium-166 microspheres, intra-arterial

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients meeting the following criteria may enter the study:
• Patients must have given written informed consent.
• Female or male aged 18 years and over.
• 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.
• Life expectancy of 12 weeks or longer.
• World Health Organisation (WHO) Performance status 0-2 (see Appendix III).
• 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.
• Negative pregnancy test for women of childbearing potential. -

You may not qualify if:

• Patients meeting any of the following criteria cannot enter the study:
• 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.
• Radiation therapy within the last 4 weeks before the start of study therapy.
• The last dose of prior chemotherapy has been received less than 4 weeks prior the start of study therapy.
• Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy.
• 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.
• Serum bilirubin \> 1.5 x Upper Limit of Normal (ULN).
• Serum creatinine \> 185 µmol/L.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \> 5 x ULN.
• Leukocytes \< 4.0 109/l and/or platelet count \< 150 109/l.
• 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.
• Pregnancy or breast feeding (women of child-bearing potential).
• 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.
• Patients with abnormalities of the bile ducts (such as stents) with a increased chance of infections of the bile ducts.
• Patients suffering from diseases with a increased chance of liver toxicity, such as primary biliary cirrhosis or xeroderma pigmentosum.

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (6)

• Vente MA, Nijsen JF, de Wit TC, Seppenwoolde JH, Krijger GC, Seevinck PR, Huisman A, Zonnenberg BA, van den Ingh TS, van het Schip AD. Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(L-lactic acid) microspheres in healthy pigs. Eur J Nucl Med Mol Imaging. 2008 Jul;35(7):1259-71. doi: 10.1007/s00259-008-0747-8. Epub 2008 Mar 11.

  PMID: 18330569 BACKGROUND

• Bult W, Vente MA, Zonnenberg BA, Van Het Schip AD, Nijsen JF. Microsphere radioembolization of liver malignancies: current developments. Q J Nucl Med Mol Imaging. 2009 Jun;53(3):325-35.

  PMID: 19521312 BACKGROUND

• Wagemans MEHM, Braat AJAT, van Rooij R, Smits MLJ, Bruijnen RCG, Prince JF, Bol GM, de Jong HWAM, Lam MGEH. Lung Mean Dose Prediction in Transarterial Radioembolization (TARE): Superiority of [166Ho]-Scout Over [99mTc]MAA in a Prospective Cohort Study. Cardiovasc Intervent Radiol. 2024 Apr;47(4):443-450. doi: 10.1007/s00270-023-03656-y. Epub 2024 Feb 7.

  PMID: 38326577 DERIVED

• 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.

  PMID: 24819055 DERIVED

• Smits ML, Nijsen JF, van den Bosch MA, Lam MG, Vente MA, Mali WP, van Het Schip AD, Zonnenberg BA. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012 Oct;13(10):1025-34. doi: 10.1016/S1470-2045(12)70334-0. Epub 2012 Aug 22.

  PMID: 22920685 DERIVED

• 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.

  PMID: 20550679 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Bernard Zonnenberg, MD, Ph.D

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator; MD, PhD

Study Record Dates

• First Submitted: December 14, 2009
• First Posted: December 15, 2009
• Study Start: December 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 31, 2012

Record last verified: 2012-01

Locations

NL (1)