Unresectable Hepatocellular CarcinomaREFINE-IONCT06117891
An Observational Study to Learn More About How Well a Treatment Works When Given After Treatment With Atezolizumab and Bevacizumab or Another Similar Combination of Drugs in Adults With Liver Cancer That Cannot be Treated With Surgery
An observational study of Unresectable Hepatocellular Carcinoma, run by Bayer at 17 sites in 12 countries.
Trial summary
This is an observational study in which only data will be collected from adults with unresectable hepatocellular carcinoma. These adults should be prescribed a different treatment after treatment with atezolizumab and bevacizumab, or another similar combination of drugs, by their doctors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma
- What is being tested?
- Atezolizumab, Bevacizumab and Durvalumab
- How many people
- 300 participants
- Where
- 17 sitesin 12 countries
- Study dates
- 27 Nov 2023to 10 Dec 2026
- Phase
- Observational
- 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
Study population: Patients with a diagnosis of uHCC treated with first-line AB or another approved 1L-IO combo and in whom a decision to treat with a second-line of systemic therapy has been made by the treating physician. The investigator or a delegate at these centers collects historic data (demographic and clinical characteristics) from medical records if available. The investigator or a delegate collects treatment-related data during visits that take place in routine practice.
Who may be able to join
- Adult patients, ≥ 18 years of age on the day of signing informed consent.
- Confirmed diagnosis of uHCC, treated in a first-line setting with AB or another approved 1L-IO combo therapy.
- Decision to initiate treatment with a second-line systemic treatment was made as per investigator's routine treatment practice prior to study enrollment.
- Signed informed consent or (for patients under legal age) signed informed assent by the patient (where applicable) and signed informed consent by parents / legal guardian.
- No participation in an investigational program with interventions outside of routine clinical practice.
Who cannot join
- Not applicable
Trial locations and contacts
17 sites in 12 countries.
17 sites in 12 countries
United States6 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Mercy Medical Center - Medline Healthcare Services LLC
Baltimore, Maryland, 21202
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203
University Of Cincinnati Division Of Hematology Oncology - UC Health System
Cincinnati, Ohio, 45219
Corporal Michael J Crescenz Department Of Veterans Affairs Medical Center
Philadelphia, Pennsylvania, 19104
Einstein Medical Center
Philadelphia, Pennsylvania, 19141
About this study
Official title: An Observational Study in Patients With Unresectable Hepatocellular Carcinoma (uHCC) Following Treatment With Atezolizumab Plus Bevacizumab (AB) or With Another Approved Immuno-oncology Immune Checkpoint Inhibitor Combination in First-line
This is an observational study in which only data will be collected from adults with unresectable hepatocellular carcinoma. These adults should be prescribed a different treatment after treatment with atezolizumab and bevacizumab, or another similar combination of drugs, by their doctors.
Unresectable hepatocellular carcinoma (uHCC) is a type of liver cancer that cannot be treated with surgery.
Read more
In the past, sorafenib was the only approved first-line anti-cancer drug for people with uHCC. Regorafenib and other drugs were approved as second-line treatments for uHCC if a person could not take sorafenib or it stopped working for them.
Lately, another first-line (1L) treatment called immuno-oncology (IO) immune checkpoint inhibitor combination (1L-IO combo), like atezolizumab with bevacizumab (AB), has become the preferred choice of treatment. This is because of the meaningful impact on patient survival. 1L-IO combo are drugs that help the body's defense system recognize and kill cancer cells.
Since the other treatments were previously approved for use following sorafenib, the best order to take these treatments in following an 1L-IO combo is unknown.
To better understand and determine this order, more knowledge is needed about how well different treatments work in participants with uHCC who have been treated with AB or another 1L-IO combo.
The main purpose of this study is to learn more about how well different treatments work when given after first-line treatment with AB or another approved 1L-IO combo. To do this, researchers will collect data on how long the participants live (also called overall survival) from the start of any treatment given after the first-line treatment.
In addition, researchers will also collect the following information to learn more about the participants who will be given a different treatment after the 1L-IO combo:
- characteristics including age, sex, and race, and signs and symptoms of the participants over the duration of their first-line treatment
- the length of time from the first to the last dose (also called duration of therapy) of the treatments given after the 1L-IO combo
- the length of time until a participant's cancer worsens, or they die (also called progression free survival) from the start of the treatments given after the 1L-IO combo
- the number of participants whose tumor completely disappears or shrinks (also called overall tumor response) after taking the treatments given after the 1L-IO combo
- the sequence of treatments given after the 1L-IO combo Data will be collected from September 2023 to December 2026 and cover a period of around 3 years. The data will be collected using medical records or by interviewing the participants during their routine visits to the doctor.
Researchers will observe participants from the start of the treatment given after the 1L-IO combo until the end of their participation in the study.
In this study, only data from routine care will be collected. No visits or tests are required as part of this study.
- Conditions
- Unresectable Hepatocellular Carcinoma
- Being tested
- Atezolizumab, Bevacizumab, Durvalumab, Tremelimumab,
- Keywords
- uHCC, systemic treatment, real-world data, prospective
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Atezolizumab combined with Bevacizumab, immune checkpoint inhibitors combination.
BevacizumabDrug
Atezolizumab combined with Bevacizumab, immune checkpoint inhibitors combination.
DurvalumabDrug
Durvalumab combined with Tremelimumab, another immuno-oncology (IO) checkpoint inhibitors combination.
Tremelimumab,Drug
Durvalumab combined with Tremelimumab, another immuno-oncology (IO) checkpoint inhibitors combination.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Patients with a diagnosis of uHCC treated with first-line AB or another approved 1L-IO combo and in whom a decision to treat with a second-line of systemic therapy has been made by the treating physician at the time of study enrollment Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Durvalumab; Drug: Tremelimumab, |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
OS is defined as the time (days) from start of second-line systemic treatment to the date of death, due to any cause. Patients alive or lost to follow-up will be censored at their last date of follow-up.
Measured: Approximately 36 months
Secondary outcomes (6)
Discriptive analysis of demographic characteristics
Measured: At baseline before the first drug administration of second-line systemic treatment
Discriptive analysis of clinical characteristics
Measured: At baseline before the first drug administration of second-line systemic treatment
Duration of therapy (DoT)
DoT in second-line setting will be calculated as the time (days) from the date of initiation of the second -line systemic treatment to the stop of this treatment regimen or to last date of follow-up, if treatment was ongoing on that date.
Measured: Approximately 36 months
Progression-free survival (PFS)
PFS is defined as the time (days) from the date of initiation of systemic treatment to the earliest date of first observed disease progression (radiological or clinical) or death due to any cause.
Measured: Approximately 36 months
Best overall response rate (ORR)
ORR will be defined according to investigator-assessed data according to local standard.
Measured: Approximately 36 months
Treatment sequences post first-line AB or other IO combinations
Measured: Approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2023
- Study start27 Nov 2023
- Primary completion10 Dec 2025
- Study completion10 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by BayerThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06117891
- Sponsor's protocol ID
- 22453
- Acronym
- REFINE-IO
- Status last verified
- Jul 2026
- First submitted
- 31 Oct 2023
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Study in Patients With Unresectable Hepatocellular Carcinoma (uHCC) Following Treatment With Atezolizumab Plus Bevacizumab (AB) or With Another Approved Immuno-oncology Immune Checkpoint Inhibitor Combination in First-line
- ClinicalTrials.gov ID
- NCT06117891
- Acronym / sponsor ID
- REFINE-IO / 22453
- Conditions
- Unresectable Hepatocellular Carcinoma
- Keywords
- uHCC, systemic treatment, real-world data, prospective
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 27 Nov 2023 (actual)
- Primary completion
- 10 Dec 2025 (actual)
- Study completion
- 10 Dec 2026 (estimated)
- First posted
- 7 Nov 2023 (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.
This is an observational study in which only data will be collected from adults with unresectable hepatocellular carcinoma. These adults should be prescribed a different treatment after treatment with atezolizumab and bevacizumab, or another similar combination of drugs, by their doctors.
Unresectable hepatocellular carcinoma (uHCC) is a type of liver cancer that cannot be treated with surgery.
In the past, sorafenib was the only approved first-line anti-cancer drug for people with uHCC. Regorafenib and other drugs were approved as second-line treatments for uHCC if a person could not take sorafenib or it stopped working for them.
Lately, another first-line (1L) treatment called immuno-oncology (IO) immune checkpoint inhibitor combination (1L-IO combo), like atezolizumab with bevacizumab (AB), has become the preferred choice of treatment. This is because of the meaningful impact on patient survival. 1L-IO combo are drugs that help the body's defense system recognize and kill cancer cells.
Since the other treatments were previously approved for use following sorafenib, the best order to take these treatments in following an 1L-IO combo is unknown.
To better understand and determine this order, more knowledge is needed about how well different treatments work in participants with uHCC who have been treated with AB or another 1L-IO combo.
The main purpose of this study is to learn more about how well different treatments work when given after first-line treatment with AB or another approved 1L-IO combo. To do this, researchers will collect data on how long the participants live (also called overall survival) from the start of any treatment given after the first-line treatment.
In addition, researchers will also collect the following information to learn more about the participants who will be given a different treatment after the 1L-IO combo:
- characteristics including age, sex, and race, and signs and symptoms of the participants over the duration of their first-line treatment
- the length of time from the first to the last dose (also called duration of therapy) of the treatments given after the 1L-IO combo
- the length of time until a participant's cancer worsens, or they die (also called progression free survival) from the start of the treatments given after the 1L-IO combo
- the number of participants whose tumor completely disappears or shrinks (also called overall tumor response) after taking the treatments given after the 1L-IO combo
- the sequence of treatments given after the 1L-IO combo Data will be collected from September 2023 to December 2026 and cover a period of around 3 years. The data will be collected using medical records or by interviewing the participants during their routine visits to the doctor.
Researchers will observe participants from the start of the treatment given after the 1L-IO combo until the end of their participation in the study.
In this study, only data from routine care will be collected. No visits or tests are required as part of this study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | – | Drug: Atezolizumab, Drug: Bevacizumab, Drug: Durvalumab, Drug: Tremelimumab,Patients with a diagnosis of uHCC treated with first-line AB or another approved 1L-IO combo and in whom a decision to treat with a second-line of systemic therapy has been made by the treating physician at the time of study enrollment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a diagnosis of uHCC treated with first-line AB or another approved 1L-IO combo and in whom a decision to treat with a second-line of systemic therapy has been made by the treating physician. The investigator or a delegate at these centers collects historic data (demographic and clinical characteristics) from medical records if available. The investigator or a delegate collects treatment-related data during visits that take place in routine practice.
Key inclusion criteria (5 listed)
- Adult patients, ≥ 18 years of age on the day of signing informed consent.
- Confirmed diagnosis of uHCC, treated in a first-line setting with AB or another approved 1L-IO combo therapy.
- Decision to initiate treatment with a second-line systemic treatment was made as per investigator's routine treatment practice prior to study enrollment.
- Signed informed consent or (for patients under legal age) signed informed assent by the patient (where applicable) and signed informed consent by parents / legal guardian.
- No participation in an investigational program with interventions outside of routine clinical practice.
Key exclusion criteria (1 listed)
- Not applicable
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 |
|---|---|---|
| AtezolizumabAtezolizumab combined with Bevacizumab, immune checkpoint inhibitors combination. | Drug | Treatment |
| BevacizumabAtezolizumab combined with Bevacizumab, immune checkpoint inhibitors combination. | Drug | Treatment |
| DurvalumabDurvalumab combined with Tremelimumab, another immuno-oncology (IO) checkpoint inhibitors combination. | Drug | Treatment |
| Tremelimumab,Durvalumab combined with Tremelimumab, another immuno-oncology (IO) checkpoint inhibitors combination. | Drug | Treatment |
Primary outcome
Overall survival (OS)
Time frame: Approximately 36 months
OS is defined as the time (days) from start of second-line systemic treatment to the date of death, due to any cause. Patients alive or lost to follow-up will be censored at their last date of follow-up.
6 secondary outcomes
Discriptive analysis of demographic characteristics
Time frame: At baseline before the first drug administration of second-line systemic treatment
Discriptive analysis of clinical characteristics
Time frame: At baseline before the first drug administration of second-line systemic treatment
Duration of therapy (DoT)
Time frame: Approximately 36 months
Progression-free survival (PFS)
Time frame: Approximately 36 months
Best overall response rate (ORR)
Time frame: Approximately 36 months
Treatment sequences post first-line AB or other IO combinations
Time frame: Approximately 36 months
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 7 Jul 2026.
- Individual participant dataSharing planned: No. Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
Related trials for Unresectable Hepatocellular Carcinoma
Not yet recruitingObservational study
Immune-Related Adverse Events and Clinical Outcomes of First-Line Immunotherapy in Egyptian Patients With Unresectable Hepatocellular Carcinoma
Hepatocellular Carcinoma, Hepatocellular Carcinoma (HCC)
Active, not recruiting
BioPearl™ Microspheres Loaded With Doxorubicin for the Treatment of Unresectable Hepatocellular Carcinoma (HCC)
Hepatocellular Carcinoma Non-resectable
RecruitingObservational study
Observational Study Protocol: LIVER-R
Hepatobiliary Cancers
Active, not recruitingPhase 2
Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver
Metastatic Cholangiocarcinoma, Metastatic Hepatocellular Carcinoma
Not yet recruiting
Overcoming Immunotherapy Resistance in Hepatocellular Carcinoma
Hepatocellular Carcinoma Non-Resectable
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.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Unresectable Hepatocellular Carcinoma, run by Bayer at 17 sites in 12 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 5 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Argentina, Brazil, China, Colombia and 7 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.
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?
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?
Overall survival (OS) (time frame: Approximately 36 months). 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 7 Jul 2026.