Holmium-166 Transarterial Radioembolization in Unresectable, Early Stage Hepatocellular Carcinoma.

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05451862

Studienbeginn:
August 2023

Letztes Update:
25.09.2023

Wirkstoff:
-

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Hepatocellular

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Terumo Europe N.V.

Collaborator:
-

Studienleiter

Jens Ricke, Prof. Dr. med
Principal Investigator
Ludwig-Maximilian-University Munich (LMU)

Wolfgang Weber, Prof. Dr. med
Principal Investigator
Munich Technische Universität (TUM)

Thomas Kröncke, Prof. Dr. med
Principal Investigator
Universitätsklinikum Augsburg

Ralph Kickuth, Prof. Dr. med
Principal Investigator
Wuerzburg University Hospital

Karin Menhart, Dr.
Principal Investigator
Universitätsklinikum Regensburg

Peter Dietrich, PD. Dr. med.
Principal Investigator
Uniklinikum Erlangen

Kontakt

Florence Chow
Kontakt:
Phone: +32(0)16 38 12 11
E-Mail: florence.chow@terumo-europe.com» Kontaktdaten anzeigen

Rijk De Jong
Kontakt:
Phone: +32(0)16 38 12 11
E-Mail: rijk.dejong@terumo-europe.com» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

LMU Klinikum
Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Jens Ricke, M.D.» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. confirmed Objective Response Rate (ORR) by localized mRECIST (Time Frame - 5 years):
ORR is defined as the proportion of patients achieving either complete or partial tumor response during the study, as assessed by blinded central image review according to localized mRECIST

Secondary outcome:

1. Best ORR based on localized mRECIST (Time Frame - 5 years):
The number and percent of patients with a confirmed response

2. Best and confirmed ORR based on mRECIST (Time Frame - 5 years):
The number and percent of patients with a confirmed response

3. Duration of Response (DoR) ≥ 6 months based on localized mRECIST and mRECIST (Time Frame - 5 years):
The number and percent of patients with a DoR ≥ 6 months. DoR is measured from time of initial response until radiological progression. Radiological progression is determined by blinded central image review according to localized mRECIST and mRECIST.

4. Time to Progression (TTP) (Time Frame - 5 years):
TTP defined as the time from treatment with QuiremSpheresTM Holmium-166 Microspheres to progression as per mRECIST

5. Progression-Free Survival (PFS) (Time Frame - 5 years):
PFS defined as the time from treatment with QuiremSpheresTM Holmium-166 Microspheres to the date of radiological progression or death from any cause. Radiological progression is determined by blinded central image review according to mRECIST

6. hepatic Progression-Free Survival (hPFS) (Time Frame - 5 years):
hPFS defined as the time from treatment with QuiremSpheresTM Holmium-166 Microspheres to the date of radiological progression in the liver or death from any cause. Radiological progression is determined by blinded central image review according to mRECIST

7. Liver transplantation rate (Time Frame - 5 years):
The number and percent of patients receiving a liver transplant

8. Liver resection rate (Time Frame - 5 years):
The number and percent of patients undergoing a liver resection

9. Overall survival (OS) (Time Frame - 5 years):
The median overall survival time

10. Safety and toxicity by evaluating the number of adverse events and the number of patients with each event (Time Frame - 5 years):
Adverse events classified by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. (including clinical and laboratory toxicity)

11. Liver function during follow-up ALBI score (Time Frame - 5 years):
ALBI score

12. Liver function during follow-up using MELD score (Time Frame - 5 years):
MELD score

13. Liver function during follow-up using Child Pugh score (Time Frame - 5 years):
Child Pugh score

14. Assessment of dosimetry and biodistribution based on quantitative assessment of imaging scans (Time Frame - 5 years):
Correlation between scout and treatment for extrahepatic dose deposition, including lung shunt and digestive shunting of QuiremSpheresTM Holmium-166 Microspheres.

15. Assessment of dosimetry and biodistribution based on quantitative assessment of imaging scans (Time Frame - 5 years):
Correlation between treatment-based absorbed dose (into the tumor and healthy liver) and clinical outcomes in terms of toxicity and efficacy (i.e. radiological response).

16. Assessment of dosimetry and biodistribution based on quantitative assessment of imaging scans (Time Frame - 5 years):
Correlation between scout-based simulated absorbed dose (into the tumor and healthy liver) and the treatment based absorbed dose (into the tumor and healthy liver).

17. Quality of Life using EQ-5D-5L questionnaire (Time Frame - 1 year):
Patient reported outcome using EQ-5D-5L questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

Geprüfte Regime

Holmium-166 treatment (QuiremSpheresTM Holmium-166 Microspheres):
Implantation into hepatic tumors by delivery via the hepatic artery for the treatment of unresectable HCC liver tumors.
Holmium-166 work-up (QuiremScoutTM Holmium-166 Microspheres):
Evaluation of lung-shunt, extrahepatic deposition and intrahepatic distribution of intra-arterially injected microspheres for patients that are eligible for TARE treatment.

Quelle: ClinicalTrials.gov

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