An interventional study of External beam radiotherapy and transarterial radioembolization in Hepatocellular Carcinoma Non-Resectable, sponsored by Radboud University Medical Center. Not yet recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-26.
Sponsored by Radboud University Medical Center · Not applicable, Interventional, and Treatment
Each year, approximately 1,000 patients in the Netherlands are diagnosed with liver cancer. When liver cancer can no longer be treated with surgery or thermal ablation, cure is no longer possible. In recent years, immunotherapy has become increasingly important in the treatment of liver cancer. Unfortunately, the combination of immunotherapy (atezolizumab) and an anti-angiogenic agent (bevacizumab) results in a durable response in only 15-20% of patients. The aim of this study is to identify a strategy to enhance the effectiveness of immunotherapy, enabling the patient's immune system to better recognize and attack the cancer.
Two recent clinical observations suggested that the immune system may be activated by external radiotherapy or radioembolization. Following these treatments, both patients unexpectedly showed regression of multiple non-irradiated liver metastases. One of these patients had initially experienced disease progression during immunotherapy, but after radiotherapy subsequently demonstrated regression of all metastatic lesions. In this clinical study (16 patients in total), we will investigate whether the immune system can be reactivated after failure of immunotherapy.
Patients will be eligible for participation after disease progression during immunotherapy for liver cancer. In Group A, eight patients will receive three fractions of external radiotherapy directed at the most dominant liver lesion or an extrahepatic metastasis. In Group B, eight patients will receive radioembolization of the most dominant liver lesion. There will be no randomization. Group A will be enrolled first, and Group B will open only after completion of enrollment in Group A.
The primary outcome measure is the number of patients in each group who achieve disease control at 6 months, defined as stable disease or tumor regression lasting for at least 6 months. During the study, participating patients will undergo extensive blood analyses, tumor biopsies of both treated and untreated lesions, and multiple CT scans.
Through these investigations, we aim to characterize the tumor microenvironment in detail, evaluate the role of different immune cell populations, and gain a better understanding of why these treatments administered after immunotherapy failure may still be capable of reactivating the immune system.
This is a prospective, non-randomized proof-of-concept clinical trial in which patients with unresectable multifocal or metastatic HCC will be treated with external beam radiotherapy (EBRT) (cohort A; n=8) or radioactive yttrium-90 based transarterial radioembolization (TARE) (cohort B; n=8) after failure of first-line systemic treatment with atezolizumab and bevacizumab to overcome immunotherapy resistance and consequently improve clinical outcome. Eligible patients will be informed about the study at the outpatient clinic.
Regular CT imaging will take place at baseline and three months post-therapy. Directly after TARE (cohort B) SPECT-CT imaging will be performed. These scans are all standard of care.
Study related blood withdrawal, and target and non-target lesion ultrasound-guided biopsies (2 biopsies per lesion) will take place:
At the described timepoints, two biopsies will be taken from the irradiated lesion as well as from a non-irradiated lesion. The second biopsy, obtained 72-120 hours after EBRT or TARE, is essential for characterizing the early treatment-induced immune response. This early time point enables the assessment of treatment-related changes in, among others, immune cell infiltration, immune cell activation, and the expression of immune-related markers. The later biopsy, obtained three months after treatment, provides insight into the more sustained and long-term effects of therapy. Comparing these two time points is crucial for understanding the dynamics and evolution of the immune response and constitutes a key research objective of this study.
Standard-of-care baseline and 3-monthly regular CT chest and abdomen will be performed until progressive disease to evaluate the primary endpoint according to RECIST v1.1.
3,251 studies on the registry are indexed under Carcinoma, Hepatocellular; 974 are open to participants now.
This study's planned enrollment of 16 is below the median of 55 across 2,347 interventional studies indexed under Carcinoma, Hepatocellular.
Browse Carcinoma, Hepatocellular studies →Radboud University Medical Center is the lead sponsor of 985 studies on the registry; 136 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Exclusion Criteria:
A potential subject who meets any of the following criteria will be excluded from participation in this study:
External beam radiotherapy
Radiation: External beam radiotherapy
transarterial radioembolization
Radiation: transarterial radioembolization
Treatment will be given according to standard-of-care procedures. Patients receive 24 Gy in 8 Gy fractions (3x 8 Gy), 2-3 times per week, using a VMAT technique and taking into account standard dose constraints for the (healthy) liver and other relevant organs at risk.
Treatment will be given according to standard-of-care procedures. The most dominant liver lesion will be treated with Y-90 based transarterial radioembolization (TARE). The initial dose-rate of yttrium-90 is lower to that of EBRT, approximately 0.7 Gy per hour versus 2 Gy per minute, respectively. The expected tumor dose will be ≥100 Gy and an acceptable healthy liver dose of ≤30 Gy will be given.
The 6-month disease control rate
The 6-month disease control rate is defined by stable disease for at least 6 months, partial responses, and complete responses of non-targeted lesions, in both cohort A and B, according to RECIST version 1.1.
Time frame: The 6-month disease control rate will be calculated from randomization to the date of the CT scan of chest and abdomen planned at 6 months post-randomization (+/- 7 days).
Objective response rate
The objective response rate is defined as the percentage of patients who experience a partial or complete response of non-targeted lesions, according to RECIST version 1.1.
Time frame: Complete duration of study up to 24 weeks
Progression-free survival
The progression-free survival is defined as the time interval from randomization to the first event of disease progression, according to RECIST version 1.1, or death, whichever comes first. Kaplan-Meier curves will be shown. This study is not designed to show differences between cohort A and B.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 60 months
Overall survival
Overall survival is calculated from the date of randomization to the date of death due to any cause. For patients alive at trial closure, date of last follow-up. Kaplan-Meier curves will be shown. This study is not designed to show differences between cohort A and B.
Time frame: From the date of randomization to the date of death from any cause assessed up to 60 months
Therapy-related toxicity
This is defined as the number of patients with any grade ≥ 3 therapy-related toxicity according to the CTCAE version 5.0.
Time frame: Up to three months after the last radiotherapy fraction (cohort A) or radio-embolization (cohort B).
Feasibility of treatment
Study feasibility of post-immunotherapy treatment is defined as: 1) the proportion of patients that complete all radiotherapy fractions (cohort A) and radioembolization (cohort B); 2) the proportion of patients that complete all study-related imaging, blood withdrawal and biopsies (cohort A and B).
Time frame: Through study completion, an average of 6 months
Health-related Quality of life
Health-Related Quality of Life (HRQoL) will be scored and reported according to the EORTC scoring manual (19). Descriptive statistics will be reported per treatment arm. Quality of Life Symptom Scale: Scores range from 1 to 4, where 1 = not at all bothered by the symptom and 4 = very much bothered by the symptom. Higher scores indicate greater symptom burden and therefore a worse outcome.
Time frame: At baseline, 72-120h post treatmen, 3 months post treatment and 6 months post treatment (EOT)
Translational immune landscape studies
In-depth translational immune landscape studies will be performed.
Time frame: Through study completion (up to approximately 18 months after the inclusion of the last patient)
Plan to share: Undecided
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Sep 2028, 23 months later.
Of 337 non-industry interventional studies with no phase under Carcinoma, Hepatocellular, half reached primary completion within 50 months of starting (the median), counting those still running; a quarter within 27 and three quarters within 75. This study's planned 23 months is below that.
Counting every sponsor, half of 357 studies reached it within 48 months; a quarter within 23 and three quarters within 75.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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