Hepatocellular Carcinoma Non-ResectableOvercomeHCCNCT07895342
Overcoming Immunotherapy Resistance in Hepatocellular Carcinoma
A study testing External beam radiotherapy and transarterial radioembolization in people with Hepatocellular Carcinoma Non-Resectable, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma Non-Resectable
- What is being tested?
- External beam radiotherapy and transarterial radioembolization
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2026to Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult individuals at least 18 years old
- Unresectable multifocal or metastatic HCC, as determined by the multidisciplinary tumor board;
- Subject has histologically or cytologically confirmed unresectable multifocal or metastatic HCC (all other histological types are excluded);
- Child-Pugh (CP) class A (well-compensated disease) or B ≤ 7 (acceptable functional compromise);
- Progressive HCC after failure of first-line atezolizumab-based systemic therapy;
- Life expectancy ≥12 weeks per investigator assessment;
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- At least one non-targeted measurable lesion per RECIST version 1.1 (the irradiated/targeted lesion in both cohorts will not be considered as measurable);
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- Agree to undergo multiple tumor biopsies, CT imaging, and blood withdrawals;
- Adequate baseline laboratory results (defined as a hemoglobin ≥5.0 mmol/l, an absolute neutrophil count ≥1.5 x 109/l, platelet count ≥75 x 109/l, creatinine clearance ≥30 ml/min, bil-irubin <3x ULN and liver transaminases ALT and AST <5x ULN);
- Allowance of temporary cessation of anticoagulants (no bridge therapy);
- Subjects must voluntarily sign and date the informed consent forms;
- Informed consent must be signed prior to any single study-related activity.
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Subjects who have received palliative radiation therapy after disease progression upon first-line treatment with atezolizumab and bevacizumab (note: prior palliative radiation therapy before or during treatment with atezolizumab and bevacizumab is allowed, provid-ed the final dose was administered ≥6 weeks before enrollment);
- Subjects who have received holmium-166 or yttrium-90 TARE after disease progression up-on first-line treatment with atezolizumab and bevacizumab (note: prior TARE before treat-ment with atezolizumab and bevacizumab is allowed);
- Large arterio-portal venous shunting per investigator assessment;
- Previous surgical hepatico-enterostomy;
- Lung shunt fraction >10%;
Show all 11Show fewer
- The presence of significant ascites
- Pregnancy or inadequate anticonception;
- History of other malignancies within 3 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%);
- Evidence of bleeding diathesis or clinically significant coagulopathy;
- Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents) or other systemic immunosuppressive medication.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Post-immunotherapy External Beam Radiotherapy or Radioembolization to Overcome Immune Checkpoint Blockade Resistance in Advanced Hepatocellular Carcinoma
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.
Read more
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.
Read the detailed description
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 baseline;
- 72-120 hours post-therapy (after last radiation fraction in cohort A; after Y-90 treatment in cohort B);
- blood withdrawal at one month post-therapy (20)
- three months post-therapy.
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.
- Conditions
- Hepatocellular Carcinoma Non-Resectable
- Being tested
- External beam radiotherapy, transarterial radioembolization
- Keywords
- radiotherapy, radioembolization, hepatocellular carcinoma, immunotherapy, EBRT, TARE
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
External beam radiotherapyRadiation
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.
transarterial radioembolizationRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | External beam radiotherapy Receives: Radiation: External beam radiotherapy |
| Arm B | Experimental | transarterial radioembolization Receives: Radiation: transarterial radioembolization |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: At baseline, 72-120h post treatmen, 3 months post treatment and 6 months post treatment (EOT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma Non-ResectableStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Participants will be assigned sequentially to one of two cohorts. The first cohort will receive external beam radiotherapy. After completion of enrollment in the first cohort, a second cohort will receive transarterial radioembolization. The cohorts are not randomized and are not intended for formal comparison.
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07895342
- Sponsor's protocol ID
- MOGE59
- Acronym
- OvercomeHCC
- Status last verified
- Oct 2026
- First submitted
- 6 Oct 2026
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-immunotherapy External Beam Radiotherapy or Radioembolization to Overcome Immune Checkpoint Blockade Resistance in Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT07895342
- Acronym / sponsor ID
- OvercomeHCC / MOGE59
- Conditions
- Hepatocellular Carcinoma Non-Resectable
- Keywords
- radiotherapy, radioembolization, hepatocellular carcinoma, immunotherapy, EBRT, TARE
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Oct 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 26 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 baseline;
- 72-120 hours post-therapy (after last radiation fraction in cohort A; after Y-90 treatment in cohort B);
- blood withdrawal at one month post-therapy (20)
- three months post-therapy.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be assigned sequentially to one of two cohorts. The first cohort will receive external beam radiotherapy. After completion of enrollment in the first cohort, a second cohort will receive transarterial radioembolization. The cohorts are not randomized and are not intended for formal comparison.
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Radiation: External beam radiotherapyExternal beam radiotherapy |
| Arm B | Experimental | Radiation: transarterial radioembolizationtransarterial radioembolization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adult individuals at least 18 years old
- Unresectable multifocal or metastatic HCC, as determined by the multidisciplinary tumor board;
- Subject has histologically or cytologically confirmed unresectable multifocal or metastatic HCC (all other histological types are excluded);
- Child-Pugh (CP) class A (well-compensated disease) or B ≤ 7 (acceptable functional compromise);
- Progressive HCC after failure of first-line atezolizumab-based systemic therapy;
Key exclusion criteria (11 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Subjects who have received palliative radiation therapy after disease progression upon first-line treatment with atezolizumab and bevacizumab (note: prior palliative radiation therapy before or during treatment with atezolizumab and bevacizumab is allowed, provid-ed the final dose was administered ≥6 weeks before enrollment);
- Subjects who have received holmium-166 or yttrium-90 TARE after disease progression up-on first-line treatment with atezolizumab and bevacizumab (note: prior TARE before treat-ment with atezolizumab and bevacizumab is allowed);
- Large arterio-portal venous shunting per investigator assessment;
- Previous surgical hepatico-enterostomy;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| External beam radiotherapyTreatment 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. | Radiation | Arm A |
| transarterial radioembolizationTreatment 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. | Radiation | Arm B |
Primary outcome
The 6-month disease control rate
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).
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.
6 secondary outcomes
Objective response rate
Time frame: Complete duration of study up to 24 weeks
Progression-free survival
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
Time frame: From the date of randomization to the date of death from any cause assessed up to 60 months
Therapy-related toxicity
Time frame: Up to three months after the last radiotherapy fraction (cohort A) or radio-embolization (cohort B).
Feasibility of treatment
Time frame: Through study completion, an average of 6 months
Health-related Quality of life
Time frame: At baseline, 72-120h post treatmen, 3 months post treatment and 6 months post treatment (EOT)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing External beam radiotherapy and transarterial radioembolization in people with Hepatocellular Carcinoma Non-Resectable, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Harm Westdorp, MD, PhD (0031 243610353, harm.westdorp@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The 6-month disease control rate (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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.