Safety and Feasibility of Radioembolization Using Ho-166 in Patients With Unresectable Hepatocellular Carcinoma

NCT05643391 | Completed

• 1 other identifier: P2020/226
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and represents a growing health problem worldwide. Most patients present locally advanced disease and are candidates for palliative transarterial locoregional treatment. Transarterial radioembolization (TARE) using 90Y has been used for more than a decade for patients with advanced disease. The use of 166Ho could offer a more personalized approach in terms of imaging and dosimetry. Aim: to evaluate the feasibility and safety of TARE using 166Ho in a selected population of HCC patients and assess the biological peripheral response to this therapy. Materials and methods: In this open-label, prospective, non-randomized, singlecenter pilot study, 20 patients with unresectable hepatocellular carcinoma will undergo TARE using 166Ho. The primary outcome is the feasibility of 166Ho radioembolization as well as the assessment of safety and toxicity profiles (CTAE V5.0). Secondary outcomes include the evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular carcinoma, according to mRECIST and metabolic criteria, as well as the impact on the tumor marker alpha-fetoprotein (AFP), assessment of biodistribution/dosimetry using a "scout dose" and time to progression (TTP). A substudy will assess the hepatic function using 99mTc-IDA hepato-biliary scintigraphy (HBS) and the comparison between "pre-scout" HBS and HBS just after "scout dose". Finally, blood samples will be collected at different time points in order to explore the biological peripheral response to these therapies. Perspectives: The newly developed 166Ho-microspheres have distinctive advantages over the existing 90Ymicrospheres with improved dosimetry that represents a prerequisite for optimal safety and efficacy.

Conditions

Hepatocellular Carcinoma

Keywords

Radioembolization; Holmium-166; Transarterial locoregional therapy

Outcome Measures

Primary Outcomes (5)

• Achievement of the selective radioembolization with Holmium-166 treatment in patients with HCC

  Feasibility will be measured by the number of completed treatments and the percentage of injected activity compared to simulation

  immediately after the SIRT session

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

  % of patients with change in clinical, biological and radiological parameters

  Day 1

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

  % of patients with change in clinical, biological and radiological parameters

  1 month

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

  % of patients with change in clinical, biological and radiological parameters

  3 months

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

  % of patients with change in clinical, biological and radiological parameters

  6 months

Secondary Outcomes (6)

• Evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular carcinoma, according to mRECIST

  3 months

• Evaluation of biodistribution/dosimetry using a scout dose

  Day 5

• Evaluation of tumor response marker alpha-fetoprotein

  Baseline,1,3,6 Months

• Time to progression (TTP)

  6 months

• Microsphere concentration derived from 1.5T MRI R2* relaxivity measurements

  Baseline and immediately after the intervention

Other Outcomes (3)

• Assess the peripheral response to TA-LRT (i.e.: serum levels of tumor necrosis factor (TNF-alfa), interleukine-6 and 8 (IL6, IL8) and vascular endothelial growth factor (VEGF) at different time points of the study)

  Baseline, day 1, day 14 and one month

• Evaluation of hepatic function using 99mTc-IDA hepato-biliary scintigraphy (HBS)

  3 months

• Comparison between "pre-scout" HBS and HBS just after "scout dose"

  Baseline and immediately after the intervention

Study Arms (1)

Single arm

EXPERIMENTAL

The treatment will include 1 preparatory angiography followed by treatment at a maximum 2 weeks interval. Dosimetry MRI will be performed just before and immediately after treatment. SPECT CT will be performed three days after treatment. The activity of 166Ho that must be administered to a patient will depend on the tumor perfusion and absorbed dose linked to this activity.Q-SuiteTM 2.0 will be used, more precisely a dosimetry software to perform an optimal compartmental predictive dosimetry: \- minimum 150 Gy to the tumor, maximum 60 Gy to non-tumoral liver, maximum 30 Gy lung shunt fraction.

Radiation: Radioembolization using Holmium-166

Interventions

Radioembolization using Holmium-166 RADIATION

This technic consists of the intra-arterial infusion of smaller beads that are loaded with a radioactive isotope (yttrium-90), and it relies on the beta radiation emitted by the isotope to induce tumor necrosis, with a minor contribution from microembolization and without risk of ischemia of the remaining liver.

Single arm

Eligibility Criteria

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

You may qualify if:

• Patients must have given written informed consent
• Adults ≥ 18 years-old
• Typical imaging or biopsy proven HCC according to EASL-EORTC guidelines (1)
• Unresectable disease, BCLC B, or contraindicated for ablation, resection or transplantation, BCLC A, or BCLC C patients with no extra-hepatic extension, patients on the waiting list for resection or transplantation.
• At least one measurable lesion on multiphasic CT or MRI
• Preserved liver function with Child- Pugh score≤ B7
• ECOG performance status ≤ 1 (Table 2)
• Life expectancy ≥3 months
• Efficient contraception for women
• Platelets ≥ 50000/m3 and PT≥ 50%
• Hemoglobin ≥8.5 g/dl
• Bilirubin ≤ 2 mg/dl
• ASAT/ALAT levels ≤ 5x upper normal limit
• Creatinine ≤ 1.5x upper normal limit

You may not qualify if:

• Before work-up:
• History of progressive, uncontrolled cancer other than HCC presenting liver metastasis.
• \>50% of liver involvement
• Portal vein thrombosis of the main branch diagnosed on contrast enhanced images. Involvement of the right or left portal main branches and more distal is accepted
• Evidence of extrahepatic disease
• Unmanageable intolerance to contrast medium
• Contraindication to hepatic angiography
• Digestive hemorrhage due to portal hypertension in the 30 days preceding treatment
• Previous systemic treatment, radiation therapy, transarterial loco-regional therapy or ablation therapy for HCC
• Active infection or untreated active hepatitis (if detectable viral HBV load, treatment with a nucleoside analog should be instituted).
• Pregnancy or breast feeding
• Ascitis
• Transjugular intrahepatic portosystemic shunt (TIPS) or portacaval shunt
• Major surgery withing 4 weeks or incompletely healed surgical incision before starting study therapy
• Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or severe depression.

Sponsors & Collaborators

• Erasme University Hospital: lead
• Terumo Europe N.V.: collaborator

Study Sites (1)

Hôpital Universitaire Erasme, ULB

Brussels, Anderlecht, 1070, Belgium

Location

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

• Gontran VERSET, MD

  Erasme University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: December 8, 2022
• Study Start: June 15, 2020
• Primary Completion: June 10, 2022
• Study Completion: December 10, 2022
• Last Updated: August 8, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)