Clinical trial NCT05451862: Holmium-166 Transarterial Radioembolization in Unresectable, Early Stage Hepatocellular Carcinoma.
Official title: Holmium-166 Transarterial Radioembolization in Unresectable, Early Stage Hepatocellular Carcinoma; a Prospective, Single-arm, Open Label, Multicenter Phase II Study: HOMIE-166.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: early stage HCC
TARE
SIRT
radioembolization
Holmium-166
Lead sponsor: Terumo Europe N.V.
Sponsor class: INDUSTRY
First posted: 2022-07-11
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 166Ho-TARE is a promising modality for the treatment of HCC, given the unique characteristics of holmium, allowing careful patient selection and personalized dosimetry treatment planning. Further clinical evidence is needed to evaluate the safety and efficacy of 166Ho-TARE in the treatment of HCC patients with limited tumor burden, well preserved liver function and performance status and ineligible for liver transplantation and/or liver resection. This study will also provide further evidence on the dose-response relationship of 166Ho-TARE in (early) HCC.

Detailed description: This is a prospective, single-arm, open-label, multicenter study with 166Ho-TARE in unresectable HCC patients with limited tumor burden and well-preserved liver function and performance status, ineligible for liver transplantation and/or liver resection. Eligibility for liver transplantation and liver resection is determined by the multidisciplinary tumor board. However, patients eligible for liver transplantation can still be included in the setting of bridge to transplant.

The study proposes to use 166Ho-TARE, including both therapeutic 166Ho-microspheres (QuiremSpheres™ Holmium-166 Microspheres) and scout 166Ho-microspheres (QuiremScout™ Holmium-166 Microspheres). All patients providing informed consent and meeting the selection criteria will be further screened using a scout dose of 166Ho-microspheres to evaluate 166Ho-TARE eligibility. Patients not eligible for selective 166Ho-TARE are considered screen failures and will not be considered as enrolled.

The primary endpoint will be assessed by blinded, independent central review, organized by an imaging core laboratory.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. Multidisciplinary tumor board decision for locoregional treatment
3. Freely given, written informed consent
4. Patients with unresectable HCC with a single nodule ≤ 8 cm or up to three nodules with a diameter of ≤ 5 cm (each) eligible for selective radioembolization (including position changes of infusion catheters)
5. Non-cirrhotic patients or Child-Pugh A cirrhosis
6. ECOG performance status 0-1
7. Using an acceptable method of contraception throughout the study until survival follow up (for subjects of childbearing potential)
8. Adequate hematological, renal and liver function.

Adequate hematological function defined as:

* Hemoglobin ≥ 6 mmol/L (9.7 g/dL)
* WBC ≥ 3.0 x 10E9/L
* Absolute neutrophil count ≥ 1.5 x 10E9/L
* Platelet count ≥ 50,000/mm3

Adequate renal function defined as:

* Serum urea and serum creatinine \< 1.5 times upper limit of normal (ULN)
* Creatinine clearance ≥ 45 ml/min

Adequate liver function defined as:

* Total bilirubin ≤ 35µmol/L (2.05 mg/dL)
* Albumin ≥ 30 g/L
* AST and ALT ≤ 5X ULN

Exclusion Criteria:

1. Diffuse and/or infiltrative HCC (defined as HCC consisting of multiple tiny liver nodules spreading throughout the entire liver or entire lobe, without a dominant nodule)
2. Hypoperfused HCC (defined as a lack of tumor blush (i.e. reduced or no uptake of contrast fluid) observed on the intra-procedural CT)
3. No full, selective arterial coverage on intra-procedural CT
4. Life expectancy \< 6 months
5. Child-Pugh score ≥7 points
6. Prior liver transplantation
7. Prior locoregional or systemic anti-cancer therapy for HCC and previous malignancies
8. Macrovascular invasion (defined as macrovascular invasion of the hepatic and/or portal vein main branches)
9. Extrahepatic metastases
10. Clinically significant ascites
11. Hepatic encephalopathy
12. Untreated active hepatitis B and/or C
13. Work-up imaging showing:

    * Lung shunt \> 30 Gy is simulated on 166Ho-scout imaging; or
    * Uncorrectable extrahepatic deposition of simulated 166Ho-scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted; or
    * Anticipated ineffective tumor targeting (\< 150 Gy mean tumor simulated absorbed dose) of 166Ho-scout for each lesion; or
    * Entire tumor burden not within the perfused liver volume (possible extrahepatic collateral supply of the tumor); or
    * Perfused liver volume \> 50% of whole liver tissue
14. Pregnant or breast-feeding
15. Current or history of cancer other than HCC, except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix
16. In the Investigator's opinion there is a reason that could limit the patient's ability to participate in the study, compliance with follow-up requirements or impact the scientific integrity of the study
17. Concurrently enrolled in another study, unless it is an observational non-interventional study

Primary outcomes:
measure: confirmed Objective Response Rate (ORR) by localized mRECIST
timeFrame: 5 years
Secondary outcomes:
measure: Best ORR based on localized mRECIST
timeFrame: 5 years
measure: Best and confirmed ORR based on mRECIST
timeFrame: 5 years
measure: Duration of Response (DoR) ≥ 6 months based on localized mRECIST and mRECIST
timeFrame: 5 years
measure: Time to Progression (TTP)
timeFrame: 5 years
measure: Progression-Free Survival (PFS)
timeFrame: 5 years
measure: hepatic Progression-Free Survival (hPFS)
timeFrame: 5 years
measure: Liver transplantation rate
timeFrame: 5 years
measure: Liver resection rate
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 5 years
measure: Safety and toxicity by evaluating the number of adverse events and the number of patients with each event
timeFrame: 5 years
measure: Liver function during follow-up ALBI score
timeFrame: 5 years
measure: Liver function during follow-up using MELD score
timeFrame: 5 years
measure: Liver function during follow-up using Child Pugh score
timeFrame: 5 years
measure: Assessment of dosimetry and biodistribution based on quantitative assessment of imaging scans
timeFrame: 5 years
measure: Assessment of dosimetry and biodistribution based on quantitative assessment of imaging scans
timeFrame: 5 years
measure: Assessment of dosimetry and biodistribution based on quantitative assessment of imaging scans
timeFrame: 5 years
measure: Quality of Life using EQ-5D-5L questionnaire
timeFrame: 1 year
Other outcomes:
Locations:
city: Munich
country: Germany
facility: LMU Klinikum
Study officials:
affiliation: Ludwig-Maximilian-University Munich (LMU)
name: Jens Ricke, Prof. Dr. med
role: PRINCIPAL_INVESTIGATOR
affiliation: Munich Technische Universität (TUM)
name: Wolfgang Weber, Prof. Dr. med
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Augsburg
name: Thomas Kröncke, Prof. Dr. med
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuerzburg University Hospital
name: Ralph Kickuth, Prof. Dr. med
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Regensburg
name: Karin Menhart, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Uniklinikum Erlangen
name: Peter Dietrich, PD. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: