Individualized Dosimetry for Holmium-166 Radioembolization in Patients With Unresectable Hepatocellular Carcinoma (RHEPaiR)

Individualized Dosimetry for Holmium-166 Radioembolization in Patients With Unresectable Hepatocellular Carcinoma; a Multi-centre, Interventional, Non-randomized, Non-comparative, Open Label, Early Phase II Study

The goal of this clinical trial is to test the safety and effectiveness of a medical device called 166-Holmium microspheres (QuiremSpheres®) in patients with hepatocellular carcinoma (HCC) . The main questions it aims to answer are:

• What is the safety and toxicity profile of the 166-Holmium microspheres?
• Is the device effective in treating HCC?

Participants will undergo a range of screening procedures to confirm they are eligible and to record their baseline results, including:

• A Computed Tomography (CT) scan
• A Magnetic Resonance Imaging (MRI) scan
• Blood tests
• Quality of life questionnaires

Before receiving treatment with QuiremSpheres® the participant will receive a 'scout' dose of the microspheres, to check whether there is distribution of the radioactivity to other non-target areas of the body. This is measured using Single-Photon Emission Computed Tomography-CT imaging. If the distribution to non-target areas is deemed to not be too high, the participant will go on to receive the individualised therapeutic dose of QuiremSpheres®. Follow-up visits will occur 3 and 6 weeks post-treatment dose, and then at 3 and 6 months.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Device: 166Holmium microspheres (QuiremSpheres®)

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rohini Sharma, Professor; Phone Number: 02033133720; Email: r.sharma@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: Rohini Sharma, Professor; Phone Number: 02033133720; Email: r.sharma@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provided written informed consent.
2. Female or male aged 18 years and over.
3. Diagnosis of HCC established according to AASLD criteria: nodule >1 cm in a patient at risk for HCC, with combination of arterial hypervascularity and venous or delayed phase wash-out on multiphase CT-scan or MRI-scan. LR-5 and LR- 4 based on Liver Imaging Reporting and Data System can be included.
4. No curative treatment options (resection, transplant, or in case of solitary tumour, RFA).
5. Life expectancy of at least 6 months.
6. ECOG Performance status 0-1.
7. Liver-dominant disease (maximum 5 lung nodules all ≤1.0 cm, solitary clinically stable adrenal metastasis, and mesenteric or portal lymph nodes all ≤2.0 cm are accepted).
8. Child-Pugh class A5-6 or B7.
9. At least one measurable liver lesion according to the modified RECIST criteria.
10. Negative pregnancy test for women of childbearing potential. Female patients of childbearing potential should use a highly effective acceptable method of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal ligation) or should be more than 1 year postmenopausal or surgically sterile during their participation in this study (from the time they sign the consent form), to prevent pregnancy.

Exclusion Criteria:

1. Evidence of significant extrahepatic disease (MRI-scan liver and multiphase abdominal CT as well as a thoracic CT are routinely performed at screening).
2. Hepatic radiation therapy within the last 4 weeks before the start of study therapy.
3. Previous or current treatment with RE. Previous treatment with TACE, surgery, RFA, and previous or current treatment with systemic treatment are allowed.
4. Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
5. Serum bilirubin > 34 umol/L in the absence of a reversible cause
6. Glomerular filtration rate <35 ml/min.
7. Non-correctable INR >1.5 in case of femoral approach (as opposed to radial).
8. Platelet count <50 109/l.
9. 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.
10. Pregnancy or breastfeeding.
11. Patients suffering from psychic disorders that make a comprehensive judgment impossible, such as psychosis, hallucinations and/or depression.
12. Patients who are declared incapacitated.
13. Previous enrolment in the present study.
14. 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.
15. Evidence of untreated, clinically significant grade 3 portal hypertension (i.e. large varices at oesophagi-gastro-duodenoscopy). In these cases, therapy with non-selective beta-blocker (propranolol) or rubber band ligation should be instituted according to accepted guidelines. In case of small varices, prophylactic propranolol is advised.
16. Portal vein thrombosis (tumour and/or bland) of the main branch (diagnosed on contrast enhanced transaxial images). Involvement of the right or left portal vein branches and more distal is accepted.
17. Untreated active hepatitis. In case of detectable viral HBV load, appropriate treatment should be instituted.
18. Transjugular intrahepatic portosystemic shunt (TIPS).
19. Body weight over 150 kg (because of maximum table load).
20. Severe allergy for intravenous contrast used (Visipaque®)
21. Lung shunt >30 Gy, as calculated using scout dose SPECT/CT.
22. Extrahepatic deposition of scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted.

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: Radioembolisation with 166Holmium microspheres	Device: 166Holmium microspheres (QuiremSpheres®); QuiremSpheres® are a biocompatible microsphere that contain the radionuclide holmium-166 (166Ho), which emits gamma-radiation (81 keV) and high-energy (1.81 MeV) beta-particles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of adverse and serious adverse events in patients receiving individualized treatment with 166Ho- microspheres, using National Cancer Institute CTCAE v5.0.	Approximately 8 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The rate of efficacy as defined as overall response rate (ORR) in patients receiving individualized treatment with 166Ho- microspheres, using modified RECIST (mRECIST) response evaluation criteria.	Approximately 8 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Terumo Europe N.V.
• Investigators: Principal Investigator: Rohini Sharma, Professor, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: RS-IC04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No