Carcinoma, HepatocellularPhase 3REPLACENCT04777851
Regorafenib-pembrolizumab vs. TACE/TARE in Intermediate Stage HCC Beyond Up-to-7
A Phase 3 study testing Regorafenib in combination with pembrolizumab and Loco-regional therapy in people with Carcinoma, Hepatocellular, run by Translational Research in Oncology at 26 sites in 13 countries.
Trial summary
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of regorafenib and pembrolizumab (Rego-Pembro) versus transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) for the first-line treatment of hepatocellular carcinoma (HCC or liver cancer). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Regorafenib in combination with pembrolizumab and Loco-regional therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 26 sitesin 13 countries
- Study dates
- 11 Oct 2023to 26 Feb 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Signed and dated Patient Informed Consent Form (PICF)
- ≥ 18 years-old at the time of PICF signature
- Confirmed diagnosis of HCC
- Intermediate-stage HCC, defined as follows:
- Multinodular HCC localized to the liver
- No evidence of MVI or EHS
Show all 19Show fewer
- Not amenable to curative treatment
- Child-Pugh Class A
- ECOG PS 0 or 1
- ALBI grade 1 or 2
- Beyond up-to-seven criteria
- Disease amenable to TACE or TARE and no contradiction to intra-arterial treatment
- Measurable disease by CT or MRI as per RECIST 1.1
- No prior systemic therapy or loco-regional therapy for HCC
- Adequate hematologic and organ function
- Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures
- Women of childbearing potential (CBP) must have confirmed negative serum pregnancy test
- Use of highly-effective contraceptive methods in women of CBP and men
- Patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection are eligible if they meet criteria as defined within the protocol
Who cannot join
- No measurable tumor of a diffuse infiltrative HCC type.
- Fibrolamellar HCC, sarcomatoid HCC or mixed hepatocellular/ cholangiocarcinoma subtypes.
- Clinically meaningful ascites.
- Prior treatment with regorafenib, a PD-1, PD-L1/PD-L2, or cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization.
- Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids.
Show all 12Show fewer
- Requirement of systemic treatment with either corticosteroids or other immunosuppressive medications ≤ 14 days prior to randomization.
- Interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, or clinically significant acute lung diseases.
- Cardiovascular conditions as defined within the protocol.
- Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed ≤ 2 years before randomization.
- Persistent proteinuria of NCI-CTCAE v5.0 Grade 3.
- Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
Trial locations and contacts
26 sites in 13 countries.
26 sites in 13 countries
France3 sites
CHU Amiens-Picardie
Amiens, 80054
Hôpital Beaujon - APHP
Clichy, 92110
Hôpital Henri Mondor
Créteil, 94010
Romania3 sites
Institutul Clinic Fundeni
Bucharest, 22328
Regional Institute of Gastroenterology and Hepatology "Dr Octavian Fodor"
Cluj-Napoca, 400394
Center of Oncology Euroclinic Victoria Hospital
Iași, 700106
South Korea3 sites
Inje University Haeundae Paik Hospital
Busan
Cha Bundang Medical Center
Seongnam-si
Severance Hospital, Yonsei University Health System
Seoul
Turkey (Türkiye)3 sites
Gülhane Eğitim ve Araştırma Hastanesi
Ankara, 6010
Gazi University MF
Ankara, 6560
Koc University Hospital
Istanbul, 34010
Belgium2 sites
UCL SAINT LUC - UC Louvain
Brussels, 1200
Antwerp University Hospital
Edegem, 2650
Georgia2 sites
JSC VIANI Batumi Referral Hospital
Batumi, 6010
Israel-Georgian Medical Research Clinic Healthycore
Tbilisi, 0112
Serbia2 sites
Clinic for Digestive Surgery, University Clinical Center of Serbia
Belgrade
Institue of Oncology Vojvodine Sremska Kamenica (Oncology Institute of Volvodina)
Kamenitz, 21204
Spain2 sites
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Miguel Servet
Zaragoza, 50009
Taiwan2 sites
National Taiwan University Hospital
Taipei, 10041
Chang Gung Memorial Hospital - Linkou
Taoyuan, 333
United States1 site
UCLA Santa Monica Hematology Oncology
Santa Monica, California, 90404
Germany1 site
Universitätsmedizin: Medizinische Klinik und Poliklinik I
Mainz, D-55131
About this study
Official title: A Phase III, Multicenter, Randomized, Open-label Trial to Evaluate the Safety and Efficacy of Systemic Therapy With Regorafenib and Pembrolizumab Versus Locoregional Therapy With Transarterial Chemoembolization or Transarterial Radioembolization, for the First-line Treatment of Intermediate-stage Hepatocellular Carcinoma With Beyond Up-to-7 Criteria
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of regorafenib and pembrolizumab (Rego-Pembro) versus transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) for the first-line treatment of hepatocellular carcinoma (HCC or liver cancer). Approximately 496 patients in around 80 clinical sites worldwide will be randomized to receive either:
- Investigational arm: Regorafenib in combination with pembrolizumab
- Control arm: Transarterial chemoembolization (TACE) or transarterial radioembolization (TARE)
In both arms, patients will receive trial treatment until progressive disease, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria is met. After trial treatment discontinuation, subsequent treatment will be administered according to the Investigator's clinical judgment.
Read the detailed description
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of systemic therapy with Rego-Pembro versus loco-regional therapy with TACE or TARE, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Approximately 496 patients (~248 in each arm) from approximately 80 sites will be randomized in order to power the trial efficiently to measure a clinically meaningful improvement for the primary endpoint, PFS according to mRECIST based on the Investigator´s assessment.
The trial will include patients who have been diagnosed with intermediate-stage HCC by biopsy, cytology or diagnostic imaging, such as dynamic computed tomography (CT) or magnetic resonance imaging (MRI), according to the criteria of the American Association for the Study of Liver Diseases (AASLD). Patients should have at least one measurable lesion per RECIST 1.1, disease not amenable to curative treatment but amenable to loco-regional therapy with TACE (cTACE or DEB-TACE) or TARE, ECOG PS 0-1, Child-Pugh class A, and beyond up-to-7 criteria.
The trial will include the following phases:
- Screening
- Treatment
- Follow-up
Randomized patients will receive either:
Investigational arm (Arm A):
-Regorafenib at a dose of 90 mg orally q.d. on days 1 to 21 of a 4-week cycle.
In combination with:
-Pembrolizumab 400 mg using a 30-minutes i.v. infusion, on day 1 (D1) of a 6-week cycle.
Control arm (Arm B):
-Patients will be treated with TACE or TARE "on-demand" according to site's standard, with the goal of controlling all known liver lesions.
In both arms, patients will receive trial treatment (Rego-Pembro or TACE/TARE) until PD per mRECIST, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria are met.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Regorafenib in combination with pembrolizumab, Loco-regional therapy
- Keywords
- Hepatocellular Carcinoma, Hepatoma, Liver Cancer, Adult, Liver Cell Carcinoma, Liver Cell Carcinoma, Adult
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib in combination with pembrolizumabDrug
Also called Stivarga® (regorafenib), Keytruda® (pembrolizumab)
Randomized patients will receive regorafenib at a dose of 90 mg per day by mouth on days 1 to 21 of a 28-day cycle, in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 (D1) of a 6-week cycle.
Loco-regional therapyProcedure or surgery
Also called Convention transarterial chemoembolization (cTACE), Drug-eluting bead transarterial chemoembolization (DEB-TACE), Transarterial Chemoembolization (TACE), Transarterial radioembolization (TARE)
Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice.
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib + Pembrolizumab | Experimental | Investigational arm: regorafenib at a dose of 90 mg orally once per day (on days 1 to 21 of a 28-day cycle), in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 of a 6-week cycle. Receives: Drug: Regorafenib in combination with pembrolizumab |
| Loco-regional therapy | Active comparator | Control arm: Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice. Receives: Procedure: Loco-regional therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) Assessed by the Investigator as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC
PFS, defined as the time (in months) from the date of randomization until the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed locally by the Investigator using mRECIST.
Measured: up to 3.5 years
Secondary outcomes (10)
Progression-free Survival (PFS) Assessed by the Investigator as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS, defined as the time (in months) from the date of randomization until the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed locally by the Investigator using RECIST 1.1.
Measured: up to 3.5 years
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST Version 1.1
PFS, defined as the time (in months) from the date of randomization until the date of PD or death due to any cause, whichever occurs first. PD will be assessed by BICR using, independently, mRECIST and RECIST 1.1.
Measured: up to 3.5 years
Overall Survival (OS) of Intermediate-Stage HCC (Rego-Pembro versus Loco-regional Therapy)
OS, defined as the time (in months) from the date of randomization until the date of death due to any cause.
Measured: up to 3.5 years
Overall Response Rate (ORR) Assessed by Investigator and Blinded Independent Central Review (BICR) as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST Version 1.1
ORR, defined as the proportion of patients who have a complete response (CR) or partial response (PR) according to RECIST v.1.1 and mRECIST, based on the Investigator's and BICR assessment.
Measured: up to 3.5 years
Time to unTACEable Progression (TTUP)
To evaluate the two treatment arms (rego-pembro versus loco-regional therapy) with respect to TTUP. TTUP, defined as the time (in months) from the date of randomization until any of the following criteria are met:
- Factors related to liver function:
- Decompensated cirrhosis (Child-Pugh class B score > 8), including jaundice, clinical hepatic encephalopathy, and refractory ascites and/or hepatorenal syndrome
- Impaired portal-vein blood flow (portal-vein thrombus, hepatofugal blood flow)
- ECOG PS ≥ 2 Note: transient post-TACE/TARE impairment of liver function of Child-Pugh class B score > 8, that return to pre-TACE/TARE values within 4 weeks of the TACE/TARE session will not qualify as TTUP.
- Factors related to HCC:
- Failure of the treated nodule to achieve Stable Disease (SD), PR or CR by mRECIST
- Malignant portal vein thrombosis
- Marcovascular invasion (MVI) or Extra-hepatic Spread (EHS)
Measured: up to 3.5 years
Duration of Response (DOR) of Rego-Pembro Versus Loco-regional Therapy
To evaluate the two treatment arms with respect to DOR. DOR, defined as the time (in months) from first documentation of response (PR or CR) to PD or death, based on Investigator's assessment or death from any cause, in patients who had a best overall response of CR or PR.
Measured: up to 3.5 years
Number of Patients with Adverse Events as Assessed by the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5
The NCI-CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading scale is provided for each AE term with unique clinical descriptions of severity based on this general guideline: Grade 1 (mild) to 5 (death). AEs will be tabulated by treatment arm, system organ class, preferred term, severity, and relationship to treatment.
Measured: up to 3.5 years
Change from Baseline in the Physical Functioning Sub-scale Score and Global Health Status/Quality of Life Scale Score as assessed by European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
To evaluate the patient reported outcomes in the two treatment arms (rego-pembro versus loco-regional therapy) as assessed by EORTC QLQ C30. EORTC QLQ C30 is a quality-of-life questionnaire to assess patients' physical, psychological and social functions. The questionnaire is composed of functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale, also several single-item symptom measures (scaling of items: 1 = Not at all to 4 = Very much; 1 = Very poor to 7 = Excellent). Scores range from 0 to 100, with a high score representing a better health-related quality of life.
Measured: up to 3.5 years
Change from Baseline in Health-related Quality of Life in Hepatocellular Carcinoma as Assessed by European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire for HCC (EORTC QLQ-HCC18)
To evaluate patient reported outcomes in the two treatment arms (rego-pembro versus loco-regional therapy) as assessed by EORTC QLQ-HCC18. EORTC QLQ-HCC18 is an 18-question module specifically to assess symptom burden and impact on health-related quality of life measuring HCC-specific symptoms. The instrument is an 18-item scale, and scores are based on a 4-point Likert scale (with 1 = 'not at all' to 4 = 'very much'); scaled scores range from 0-100 with a higher score indicating worse symptoms.
Measured: up to 3.5 years
Change from Baseline in Health-Related Quality of Life as Assessed by the EuroQol's 5-level EQ-5D Health Questionnaire (EQ-5D-5L)
To evaluate patient reported outcomes for health-related quality of life in the two treatment arms (rego-pembro versus loco-regional therapy) as assessed by health questionnaire EQ-5D-5L. Each dimension (Mobility, Self-care, Usual activities, Pain \& discomfort, Anxiety \& depression) in the EQ-5D-5L has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). There are 3,125 possible health states defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health).
Measured: up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2021
- Study start11 Oct 2023
- Primary completion26 Feb 2026
- Study completion26 Feb 2026
Why it stopped: The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Translational Research in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Peter R Galle, MD, Study chair, University Medical Center, Mainz, GermanyRichard S Finn, MD, Study chair, UCLA Department of Medicine, Division of Hematology-Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04777851
- Sponsor's protocol ID
- TRIO041
- Other IDs
- EU CT # 2022-501969-42-00
- Acronym
- REPLACE
- Status last verified
- Mar 2026
- First submitted
- 25 Feb 2021
- Last updated
- 9 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicenter, Randomized, Open-label Trial to Evaluate the Safety and Efficacy of Systemic Therapy With Regorafenib and Pembrolizumab Versus Locoregional Therapy With Transarterial Chemoembolization or Transarterial Radioembolization, for the First-line Treatment of Intermediate-stage Hepatocellular Carcinoma With Beyond Up-to-7 Criteria
- ClinicalTrials.gov ID
- NCT04777851
- Acronym / sponsor ID
- REPLACE / TRIO041
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Hepatocellular Carcinoma, Hepatoma, Liver Cancer, Adult, Liver Cell Carcinoma, Liver Cell Carcinoma, Adult
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Translational Research in OncologyUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 11 Oct 2023 (actual)
- Primary completion
- 26 Feb 2026 (actual)
- Study completion
- 26 Feb 2026 (actual)
- First posted
- 2 Mar 2021 (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.
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of regorafenib and pembrolizumab (Rego-Pembro) versus transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) for the first-line treatment of hepatocellular carcinoma (HCC or liver cancer). Approximately 496 patients in around 80 clinical sites worldwide will be randomized to receive either:
- Investigational arm: Regorafenib in combination with pembrolizumab
- Control arm: Transarterial chemoembolization (TACE) or transarterial radioembolization (TARE)
In both arms, patients will receive trial treatment until progressive disease, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria is met. After trial treatment discontinuation, subsequent treatment will be administered according to the Investigator's clinical judgment.
Detailed description
REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of systemic therapy with Rego-Pembro versus loco-regional therapy with TACE or TARE, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Approximately 496 patients (~248 in each arm) from approximately 80 sites will be randomized in order to power the trial efficiently to measure a clinically meaningful improvement for the primary endpoint, PFS according to mRECIST based on the Investigator´s assessment.
The trial will include patients who have been diagnosed with intermediate-stage HCC by biopsy, cytology or diagnostic imaging, such as dynamic computed tomography (CT) or magnetic resonance imaging (MRI), according to the criteria of the American Association for the Study of Liver Diseases (AASLD). Patients should have at least one measurable lesion per RECIST 1.1, disease not amenable to curative treatment but amenable to loco-regional therapy with TACE (cTACE or DEB-TACE) or TARE, ECOG PS 0-1, Child-Pugh class A, and beyond up-to-7 criteria.
The trial will include the following phases:
- Screening
- Treatment
- Follow-up
Randomized patients will receive either:
Investigational arm (Arm A):
-Regorafenib at a dose of 90 mg orally q.d. on days 1 to 21 of a 4-week cycle.
In combination with:
-Pembrolizumab 400 mg using a 30-minutes i.v. infusion, on day 1 (D1) of a 6-week cycle.
Control arm (Arm B):
-Patients will be treated with TACE or TARE "on-demand" according to site's standard, with the goal of controlling all known liver lesions.
In both arms, patients will receive trial treatment (Rego-Pembro or TACE/TARE) until PD per mRECIST, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria are met.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regorafenib + Pembrolizumab | Experimental | Drug: Regorafenib in combination with pembrolizumabInvestigational arm: regorafenib at a dose of 90 mg orally once per day (on days 1 to 21 of a 28-day cycle), in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 of a 6-week cycle. |
| Loco-regional therapy | Active comparator | Procedure: Loco-regional therapyControl arm: Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed and dated Patient Informed Consent Form (PICF)
- ≥ 18 years-old at the time of PICF signature
- Confirmed diagnosis of HCC
- Intermediate-stage HCC, defined as follows:
- Beyond up-to-seven criteria
Key exclusion criteria (12 listed)
- No measurable tumor of a diffuse infiltrative HCC type.
- Fibrolamellar HCC, sarcomatoid HCC or mixed hepatocellular/ cholangiocarcinoma subtypes.
- Clinically meaningful ascites.
- Prior treatment with regorafenib, a PD-1, PD-L1/PD-L2, or cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization.
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 |
|---|---|---|
| Regorafenib in combination with pembrolizumabAlso: Stivarga® (regorafenib), Keytruda® (pembrolizumab)Randomized patients will receive regorafenib at a dose of 90 mg per day by mouth on days 1 to 21 of a 28-day cycle, in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 (D1) of a 6-week cycle. | Drug | Regorafenib + Pembrolizumab |
| Loco-regional therapyAlso: Convention transarterial chemoembolization (cTACE), Drug-eluting bead transarterial chemoembolization (DEB-TACE), Transarterial Chemoembolization (TACE), Transarterial radioembolization (TARE)Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice. | Procedure or surgery | Loco-regional therapy |
Primary outcome
Progression-free Survival (PFS) Assessed by the Investigator as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC
Time frame: up to 3.5 years
PFS, defined as the time (in months) from the date of randomization until the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed locally by the Investigator using mRECIST.
10 secondary outcomes
Progression-free Survival (PFS) Assessed by the Investigator as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: up to 3.5 years
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST Version 1.1
Time frame: up to 3.5 years
Overall Survival (OS) of Intermediate-Stage HCC (Rego-Pembro versus Loco-regional Therapy)
Time frame: up to 3.5 years
Overall Response Rate (ORR) Assessed by Investigator and Blinded Independent Central Review (BICR) as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST Version 1.1
Time frame: up to 3.5 years
Time to unTACEable Progression (TTUP)
Time frame: up to 3.5 years
Duration of Response (DOR) of Rego-Pembro Versus Loco-regional Therapy
Time frame: up to 3.5 years
Number of Patients with Adverse Events as Assessed by the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5
Time frame: up to 3.5 years
Change from Baseline in the Physical Functioning Sub-scale Score and Global Health Status/Quality of Life Scale Score as assessed by European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
Time frame: up to 3.5 years
Change from Baseline in Health-related Quality of Life in Hepatocellular Carcinoma as Assessed by European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire for HCC (EORTC QLQ-HCC18)
Time frame: up to 3.5 years
Change from Baseline in Health-Related Quality of Life as Assessed by the EuroQol's 5-level EQ-5D Health Questionnaire (EQ-5D-5L)
Time frame: up to 3.5 years
Results and safety
The study was stopped early (reason given: The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2026.
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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. This study is not recruiting at the moment.
Peter R Galle, MD study chair
University Medical Center, Mainz, Germany
Richard S Finn, MD study chair
UCLA Department of Medicine, Division of Hematology-Oncology
26 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Regorafenib in combination with pembrolizumab and Loco-regional therapy in people with Carcinoma, Hepatocellular, run by Translational Research in Oncology at 26 sites in 13 countries.
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 19 inclusion and 12 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: stopped early, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in France, Romania, South Korea, Turkey (Türkiye), Belgium and 8 more countries. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The trial ended earlier than planned due to slow enrolment, which has made it unfeasible to achieve the target sample size within a reasonable timeframe. Consequently, a business decision has been made to discontinue funding for the trial.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) Assessed by the Investigator as per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC (time frame: up to 3.5 years). 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 9 Mar 2026; AzTrials last refreshed its copy on 7 Nov 2026.