Individualized Dosimetry for Holmium-166-radioembolization in Patients With Unresectable Hepatocellular Carcinoma

NCT05114148 | Unknown

• 1 other identifier: NL74751.041.21
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with hepatocellular carcinoma often die from intrahepatic disease because current treatment options are limited. Local treatment using 166Ho-radioembolization (166Ho-RE) offers a safe and effective treatment. Because 166Ho-microspheres are used as a scout dose for treatment simulaton and for the actual treatment itself, a tailored approach can be used. This concept has proven to be more predictive than the 90Y-radioembolization concept (current standard-of-care), which is a based on a surrogate scout dose (i.e. 99mTc-MAA). A personal treatment plan may be used for 166Ho-radioembolization to optimize efficacy, based on scout dose distribution. However, individualized treatment planning inherently leads to treatment doses that deviate from the currently approved 'one-size-fits-all' approach (i.e. 60 Gy average absorbed dose for all patients). Therefore, safety of individualized 166Ho-RE will be evaluated first to validate safety and confirm safety thresholds. These thresholds will be used in subsequent randomized controlled studies.

Conditions

Hepatocellular Carcinoma Non-resectable

Outcome Measures

Primary Outcomes (1)

• Rate of unacceptable toxicity.

  For this study, unacceptable toxicity is defined as the occurrence of RE-induced liver disease, defined as a total bilirubin increase grade 3 or higher according to the CTCAE version 4.03, in combination with ascites and low albumin, in the absence of disease progression. Any (suspected unexpected) serious adverse event of (suspected unexpected) serious device effect that is possibly, probably or definitely related to study treatment will also be regarded unacceptable toxicity.

  6 months

Secondary Outcomes (8)

• Rate of respons

  6 months

• Anti-tumor effect (alfa-fetoprotein).

  6 months

• The correlation between tumor absorbed dose in Gy and rate of response according to modified RECIST.

  6 months

• The correlation between non-tumor liver absorbed dose in Gy and rate of unacceptable toxicity.

  6 months

• EORTC Quality of Life questionnaire number C30

  6 months

Study Arms (1)

Holmium-166 radioembolization

EXPERIMENTAL

Individualized holmium-166 radioembolization will be performed via a catheter during angiography. Dosimetry-based treatment planning will be individualized based on Q-Suite™ software.

Device: Holmium-166 radioembolization

Interventions

Holmium-166 radioembolization DEVICE

Individualized 166Ho-RE will be performed via a catheter during angiography. Dosimetry-based treatment planning will be individualized based on Q-Suite™ software.

Holmium-166 radioembolization

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Patients must have given written informed consent.
• Female or male aged 18 years and over.
• Diagnosis of HCC established according to the Netherlands HCC guideline criteria (in line with American 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.2, 4 LR-5 and LR- 4 based on Liver Imaging Reporting and Data System can be included based on discretion of the principal investigator.
• No curative treatment options (resection, transplant, or in case of solitary tumor \<5 cm, RFA).
• Life expectancy of at least 6 months.
• ECOG Performance status 0-1 (Table 2).
• 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).
• Child-Pugh class A5-6 or B7.
• At least one measurable liver lesion according to the modified RECIST criteria.(26)
• 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.

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Evidence of significant extrahepatic disease (MRI-scan liver and multiphase abdominal CT as well as a thoracic CT are routinely performed at screening).
• Hepatic radiation therapy within the last 4 weeks before the start of study therapy.
• Previous or current treatment with RE. Previous treatment with TACE, surgery, RFA, and previous or current treatment with sorafenib are allowed.
• Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
• Serum bilirubin \>34.2 micromole/L (2 mg/dL).
• Glomerular filtration rate \<35 ml/min.
• Non-correctable INR \>1.5 in case of femoral approach (as opposed to radial).
• Leukocytes \<2 109/l and/or platelet count \<50 109/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 breastfeeding.
• Patients suffering from psychic disorders that make a comprehensive judgment impossible, such as psychosis, hallucinations and/or depression.
• Patients who are declared incapacitated.
• Previous enrollment in the present study.
• 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.

Sponsors & Collaborators

• UMC Utrecht: lead
• Erasmus Medical Center: collaborator
• Terumo Corporation: collaborator

Study Sites (1)

UMC Utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Nuclear Medicine

Model Details: Multi-center, interventional, treatment, non-randomized, open label, non-comparative, early clinical safety study. The study is a collaboration between UMC Utrecht and Erasmus MC Rotterdam.

Study Record Dates

• First Submitted: October 1, 2021
• First Posted: November 9, 2021
• Study Start: March 1, 2022
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2025
• Last Updated: November 10, 2022

Record last verified: 2022-11

Locations

NL (1)