Hepatobiliary CancersLIVER-RNCT06252753
Observational Study Protocol: LIVER-R
An observational study of Hepatobiliary Cancers, run by AstraZeneca at 160 sites in 22 countries.
Trial summary
Given the number of anticipated durvalumab-based treatment launches in the hepatobiliary cancer space over the next 3 years, there is a need to capture contemporary real-world data across these indications. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Hepatobiliary Cancers
- What is being tested?
- Durvalumab-based combination therapies in observational study setting, Non Durvalumab-based therapies in observational study setting and Durvalumab-based combination therapies in observational study settings
- How many people
- 4,000 participants
- Where
- 160 sitesin 22 countries
- Study dates
- 20 Dec 2023to 30 Dec 2030
- 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 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population includes patients treated with durvalumab-based and non durvalumab-based regimens for hepatobiliary cancer as part of routine clinical practice. The decision to treat patients with a durvalumab based regimen should be independent from the decision to enroll patients in the study.
Who may be able to join
- All patients must meet all of the following general criteria 1-4 along with all respective cohort specific criteria noted below:
- Age ≥18 years and a lawful adult in the country at the index date
- Confirmed presence of malignancy of primary hepatobiliary cancer by any method (e.g., radiological, histological, etc.)
- Decision to treat was made independently and prior to obtaining informed consent
- Informed consent was obtained as per country level regulations (includes waiver of consent for retrospective data collection if approved)
- aBTC Specific Inclusion Criteria
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- A patient will be eligible to be included in the aBTC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- Patient has unresectable aBTC
- Has received or is intending to receive a durvalumab-based regimen (may have been treated in an EAP)
- uHCC Specific Inclusion Criteria
- A patient will be eligible to be included in the uHCC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- Patient has unresectable uHCC
- Not eligible for LRT, as well as for those who progressed following LRT
- Has received or is intending to receive a durvalumab-based regimen (may have been treated in an EAP)
- eeHCC Specific Inclusion Criteria
- A patient will be eligible to be included in the eeHCC cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- HCC confirmed by radiological or histological diagnosis
- Child-Pugh A-B7
- Disease not amenable to curative treatment but amenable to LRT at index
- Patients with liver-confined HCC who initiated first non-curative intent LRT on or after 01 January 2024
- Patients eligible for LRT with palliative intent such as TACE/ TARE/transarterial infusion chemotherapy (TAIC)/ hepatic arterial infusion chemotherapy (HAIC)/transarterial embolization (TAE) given by itself or in combination with other systemic therapy (can include durvalumab) within 60 days of the LRT
- EMERALD Specific Inclusion Criteria
- A patient will be eligible to be included in the EMERALD cohort if they meet all general inclusion criteria 1-4 in addition to the following criteria:
- HCC confirmed by radiological or histological diagnosis
- Child-Pugh score of A-B7
- Liver-confined disease not amenable to curative treatment but amenable to LRT at index
- Receipt of a durvalumab-based regimen in combination with LRT administered within 28 days of each other (index is the first of the two treatments administered)
Who cannot join
- General Exclusion Criteria
- A patient will be excluded from participating in this study if they meet any of the following general criteria 1-2 or any cohort specific exclusion criteria:
- Currently/was participating or plans to participate in any clinical trial for investigational treatment for hepatobiliary cancers on or after the diagnosis date until the index date
- Second primary malignancy prior to HCC or BTC diagnosis
- aBTC Specific Exclusion Criteria
- A patient will be excluded from participating in the aBTC cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
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- Received a liver transplant during the baseline period
- Received more than 1 cycle of Gemcitabine + Cisplatin for biliary tract cancer on or after diagnosis of unresectable, locally advanced or metastatic disease through the index date. Patients who received any systemic therapy while having early stage, resectable disease are eligible
- uHCC Specific Exclusion Criteria
- A patient will be excluded from participating in the uHCC cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
- Received a liver transplant during the baseline period
- Received other systemic therapies for hepatobiliary cancer indication on or after diagnosis date through the index date
- eeHCC Specific Exclusion Criteria
- A patient will be excluded from participating in the eeHCC cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
- Eligible for curative therapy at the time of receiving LRT (ablation)
- Extrahepatic spread
- Portal vein tumor thrombosis (PVTT) of VP3/4
- Receipt of systemic therapy prior to index LRT in the baseline period
- Liver transplant any time prior to index
- EMERALD Specific Exclusion Criteria
- A patient will be excluded from participating in the EMERALD cohort if they meet any of the general exclusion criteria 1-2 or any of the following criteria:
- Eligible for curative therapy at the time of receiving LRT (ablation)
- Extrahepatic spread
- Portal vein tumor thrombosis (PVTT) of VP3/4
- Receipt of systemic therapy prior to index LRT in the baseline period
- Liver transplant any time prior to index
Trial locations and contacts
160 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
160 sites in 22 countries
Germany33 sites, 32 recruiting
- Recruiting
Research Site
Aachen, North Rhine-Westphalia, 52074
- Terminated
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Augsburg, Bavaria, 86150
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Berlin, 13353
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Berlin, 14165
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Bochum, North Rhine-Westphalia, 44892
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Bremen, 28211
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Bremenhaven, Free Hanseatic City of Bremen, 27574
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Cologne, North Rhine-Westphalia, 50937
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Dortmund, North Rhine-Westphalia, 44137
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Dresden, Saxony, 1307
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Göttingen, Lower Saxony, 37075
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Halle, Saxony-Anhalt, 06108
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Hamburg, 20259
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Hamburg, 22291
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Hanover, Lower Saxony, 30161
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Hanover, Lower Saxony, 30459
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Heidenheim, Baden W Rttemberg, 89522
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Kassel, Hesse, 34125
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Koblenz, Rhineland-Palatinate, 56073
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Konstanz, Baden-W Rttemberg, 78484
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Leipzig, Saxony, 4103
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Magdeburg, Saxony-Anhalt, 39120
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Mannheim, Baden-W Rttemberg, 68167
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Marburg, Hesse, 35033
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Moers, North Rhine-Westphalia, 47441
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Munich, Bavaria, 81377
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Neumünster, Schleswig-Holstein, 24534
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Rostock, Mecklenburg-Vorpommern, 18057
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Schorndorf, Baden-Wurttemberg, 73614
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Stolberg, North Rhine-Westphalia, 52222
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Stuttgart, Baden-Wurttemberg, 70174
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Wiesbaden, Hesse Land, 65189
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Zwickau, Saxony, 8060
United States24 sites, 24 recruiting
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Augusta, Georgia, 30912
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Baton Rouge, Louisiana, 70808
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Bethlehem, Pennsylvania, 18015
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Birmingham, Alabama, 35233-1932
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Boston, Massachusetts, 02215
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Canton, Ohio, 44718
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Clermont, Florida, 34711
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Coronado, California, 92118
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Dallas, Texas, 75390-8567
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Evergreen Park, Illinois, 60805
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Gainesville, Florida, 32610
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Hinsdale, Illinois, 60521
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Lancaster, Pennsylvania, 17604
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Los Angeles, California, 90048
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Mobile, Alabama, 36604
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Osage Beach, Missouri, 65065
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Philadelphia, Pennsylvania, 19141
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Phoenix, Arizona, 85004
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Pittsburgh, Pennsylvania, 15212
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Spokane, Washington, 99204
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Tampa, Florida, 33606
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Temple, Texas, 76508
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Walnut Creek, California, 94598
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White Plains, New York, 10601
Spain18 sites, 18 recruiting
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Barcelona, 8035
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Burgos, Castile-Le N, 9006
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El Palmar, Murcia, 30120
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Madrid, 28007
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Madrid, 28034
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Madrid, 28040
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Madrid, 28041
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Majadahonda, Madrid, 28222
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Ourense, Galicia, 32005
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Oviedo, 33011
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Pamplona, 31008
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Poniente Sur, C Rdoba, 14004
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Santa Cruz de Tenerife, 38010
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Santander, Cantabria, 39008
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Santiago de Compostela, A Coru A, 15706
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Seville, 41009
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Valencia, 46010
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Zaragoza, Aragon, 50009
France10 sites, 10 recruiting
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Avignon, Provence-Alpes-Côte d'Azur Region, 84918
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Boulogne-sur-Mer, Hauts-de-France, 62200
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Grenoble, Auvergne-Rh ne-Alpes, 38700
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Marseille, Provence-Alpes-Côte d'Azur Region, 13008
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Mulhouse, Grand Est, 68100
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Paris, Île-de-France Region, 75012
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Paris, Île-de-France Region, 75014
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Poitiers, New Aquitaine, 86000
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St-Malo, Brittany Region, 35403
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Strasbourg, Alsace, 67000
Italy10 sites, 10 recruiting
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Brescia, Lombardy, 25123
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Milan, Lombardy, 20132
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Milan, Lombardy, 20133
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Monserrato, Sardinia, 09042
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Naples, Campania, 80131
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Pisa, Tuscany, 56124
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Rome, Lazio, 00128
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Rome, Lazio, 00168
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Rozzano, Lombardy, 20089
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Turin, Piedmont, 10126
Japan8 sites, 8 recruiting
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Kanazawa, Ishikawa-ken, 920-8641
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Kashiwa-shi, Chiba, 277-8577
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Kurume, Fukuoka, 830-0011
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Kyoto, Kyoto, 606-8507
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Nagoya, Aichi-ken, 466-8550
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Ōsaka-sayama, Osaka, 589-8511
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Sendai, Miyagi, 980-8574
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Yokohama, Kanagawa, 241-8515
Belgium6 sites, 6 recruiting
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Bonheiden, Antwerp, 2820
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Brussels, Anderlecht, 1070
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Edegem, Antwerp, 2650
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Leuven, Brabant, 3000
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Liège, Wallonia, 4000
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Stene, West Flanders, 8400
Brazil6 sites, 6 recruiting
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Curitiba, Paraná, 81480-580
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Morumbi, São Paulo, 05651-901
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Porto Alegre, Rio Grande do Sul, 90035-001
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Recife - PE, Recife - PE, 50070-490
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São Paulo, 01246-000
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São Paulo, 04538-132
Greece6 sites, 6 recruiting
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Athens, Attica, 11527
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Athens, Attica, 14564
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Chaïdári, Athens, 12462
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Larissa, Thessaly, 41110
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Thessaloniki, Central Macedonia, 54639
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Thessaloniki, Central Macedonia, 55236
Taiwan5 sites, 5 recruiting
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Kaohsiung City, 82445
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Taichung, Taichung City, 40705
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Taipei, 100225
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Taipei, 11217
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Taoyuan City, 33305
Australia4 sites, 4 recruiting
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Garran, Australian Capital Territory, 2605
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Heidelberg, Victoria, 3084
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Melbourne, Victoria, 3004
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Murdoch, Western Australia, 6150
Canada4 sites, 4 recruiting
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Calgary, Alberta, T2N 4N2
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Edmonton, Alberta, T6G-1Z2
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Halifax, Nova Scotia, B3H 2Y9
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London, Ontario, N6A 5W9
Israel4 sites, 4 recruiting
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Jerusalem, 9103102
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Nahariya, Northern Didstrict, 22100
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Ramat Gan, Tel Aviv, 52621
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Tel Aviv, 6423906
Portugal4 sites, 4 recruiting
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Faro, 8000-386
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Lisbon, 1400 - 038
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Lisbon, 1649-028
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Vila Real, North, 5000-508
Romania4 sites, 4 recruiting
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Bucharest, 22328
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Cluj-Napoca, 400162
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Craiova, 200347
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Iași, 700483
Austria3 sites, 3 recruiting
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Linz, Upper Austria, 4010
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Sankt Pölten, Lower Austria, 3100
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Vienna, State of Vienna, 1090
Norway2 sites, 2 recruiting
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Bergen, Hordaland, 5021
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Oslo, Ostlandet, 379
Saudi Arabia2 sites, 2 recruiting
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Jeddah, Mecca Region, 22384
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Riyadh, Ar Riyadh, 12231
Singapore2 sites, 2 recruiting
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Singapore, 169610
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Singapore, 329563
Switzerland2 sites, 2 recruiting
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Lausanne, Canton of Vaud, 1005
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Zurich, 8032
United Arab Emirates2 sites, 2 recruiting
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Deira, Dubai, 7272
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Mohammed Bin Zayed City, Abu Dhabi Emirate, 92510
Puerto Rico1 site, 1 recruiting
- Recruiting
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San Juan, Rio Piedras, 00935
About this study
Official title: An Observational Multi-Center Study to Evaluate Real-World Treatment Outcomes With or Without Durvalumab-Based Regimens in Hepatobiliary Cancers
Given the number of anticipated durvalumab-based treatment launches in the hepatobiliary cancer space over the next 3 years, there is a need to capture contemporary real-world data across these indications. LIVER-R is a multi-country, multi-center, observational study of patients with a confirmed diagnosis of hepatobiliary cancer treated with or without a durvalumab-based regimen as part of routine clinical practice or early access program (EAP). The study design will include primary and secondary data collection. The primary objective of this study is to evaluate the effectiveness of regimens (durvalumab-based or otherwise) in real-world settings as measured by real-world overall survival. Other endpoints include demographics, clinical characteristics, clinically significant events of interest, treatment patterns, concomitant medications, treatment provider characteristics, and other real-world clinical endpoints (such as duration of treatment, progression-free survival, time to treatment progression, time to next treatment, time to treatment discontinuation, recurrence-free survival, and time to treatment recurrence ).
Read the detailed description
LIVER-R is a real-world, multi-country, multi-centre study aiming to enroll approximately 4,000 patients across hepatobiliary cohorts (approximately 1,385 patients for aBTC, approximately 1,165 patients for uHCC, approximately 1,000 patients for eeHCC, and approximately 400 patients for EMERALD) across multiple countries from North and South America, Europe, the Middle East and the Asia-Pacific region. The study design will include primary and secondary data collection. Primary data will be collected in real-time during the patient's routine visit. Secondary data will be collected from the patient's medical record at enrollment and at prespecified study time points (6-month intervals). The study population includes adult patients whose physician has previously made the decision to treat them with or without a durvalumab-based regimen for hepatobiliary cancer as part of routine clinical practice or patients receiving treatment through EAP. The study will include a baseline period of up to 5 years before the index date (initiation of a durvalumab-based or non durvalumab-based regimen) and a follow-up period to the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years. This is a descriptive, noncomparative study. No formal hypotheses are to be tested. All descriptive analyses will be conducted separately for each primary hepatobiliary cancer indication. Kaplan Meier estimates will be produced for time-to-event outcomes.
- Conditions
- Hepatobiliary Cancers
- Being tested
- Durvalumab-based combination therapies in observational study setting, Non Durvalumab-based therapies in observational study setting, Durvalumab-based combination therapies in observational study settings
- Keywords
- Hepatobiliary cancer, Unresectable hepatocellular carcinoma (uHCC), embolization eligible uHCC (eeHCC), Advanced biliary tract cancer (aBTC), Durvalumab, Observatory, Real-world
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Durvalumab-based combination therapies in observational study settingOther
Also called Imfinzi
Data on patients who initiated durvalumab-based regimens, including STRIDE (Single Tremelimumab Regular Interval Durvalumab), will be collected).
Durvalumab-based combination therapies in observational study settingOther
Also called Imfinzi
Data on patients who initiated durvalumab-based regimens, including durvalumab + chemotherapy combinations (e.g., Durvalumab + GemCis etc.) will be collected.
Non Durvalumab-based therapies in observational study settingOther
Data on patients who initiated non durvalumab-based regimens, including LRT alone or LRT followed by systemic therapies, will be collected.
Durvalumab-based combination therapies in observational study settingsOther
Also called Imfinzi
Data on patients who initiated durvalumab-based regimens in combination with LRT, will be collected
| Study group | Role | What they receive |
|---|---|---|
| unresectable hepatocellular carcinoma (uHCC) | advanced uHCC patients who had not received prior systemic therapy and were not eligible for LRT, as well as those who had progressed following LRT, and who have received a durvalumab-based regimen Receives: Other: Durvalumab-based combination therapies in observational study setting | |
| advanced biliary tract cancer (aBTC) | patients with advanced BTC (aBTC) who are not eligible for resection and who have received a durvalumab-based regimen Receives: Other: Durvalumab-based combination therapies in observational study setting | |
| eeHCC | uHCC patients with liver-confined disease not amenable to curative treatment but amenable to LRT who receive LRT alone or LRT followed by systemic therapy within 60 days (if administered in combination, LRT must be received first) Receives: Other: Non Durvalumab-based therapies in observational study setting | |
| EMERALD | uHCC patients with liver-confined disease not amenable to curative treatment but amenable to LRT who receive durvalumab-based regimens in combination with LRT (durvalumab and LRT are given within 28 days of each other, regardless of order) Receives: Other: Durvalumab-based combination therapies in observational study settings |
What is being measured
The primary outcome is the main question the study is designed to answer.
Real-world overall survival (rwOS) in all participants
rwOS will be calculated as the time from the index date to date of death, by any cause.
Measured: rwOS will be assessed as OS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median OS for a minimum follow-up of 2 years.
Secondary outcomes (14)
Clinically significant events (CSEs) of interest leading to a medical intervention in all participants
CSEs of interest leading to medical intervention including treatment interruption, discontinuation, hospitalization, or which require interventions of concomitant use of corticosteroids, immunosuppressants and/or endocrine therapies will be captured for the enrolled patients.
Measured: CSEs will be captured from the index date through 90 days after the last administration of durvalumab-based or non durvalumab-based regimens or death, whichever occurs first.
Patient demographic and clinical characteristics in all participants
Descriptive statistics will be used to describe demographic and clinical characteristics for the enrolled patients.
Measured: Patient demographic and clinical characteristics will be captured up to 5 years prior to the index date.
Characterize the durvalumab-based regimen and/or LRT treatment patterns in all participants
Treatment patterns of the index durvalumab-based regimen or LRT will be described.
Treatment patterns of therapies administered both before and after the first administration of index durvalumab-based regimen or LRT will be described.
Measured: Treatment patterns will be captured from the index date until the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years.
Real-world duration of treatment (rwDOT) in all participants
rwDOT will be calculated as the time from the index date to date of discontinuation of the index durvalumab-based regimen or LRT.
Measured: rwDOT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median DOT for a minimum follow-up of 2 years.
Real-world progression free survival (rwPFS) in all participants
rwPFS will be calculated as the time from the index date to the earliest date of documented disease progression as determined by the physician's assessment or death.
Measured: rwPFS will be assessed as PFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median PFS for a minimum follow-up of 2 years.
Real-world time to progression (rwTTP) in all participants
rwTTP will be calculated as the time from the index date to the date of documented disease progression as determined by the physician's assessment.
Measured: rwTTP will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTP for a minimum follow up of 2 years.
Real-world time to next treatment (rwTTNT) in all participants
rwTTNT will be calculated as the time from the index date (first-line treatment date) to the date of initiation of the next treatment. rwTTNT will also be assessed for subsequent lines of therapy among patients who started a second line of therapy until a third line of therapy, patients who started a third line of therapy until a fourth line of therapy (rwTTNT), etc.
Measured: rwTTNT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTNT for a minimum follow-up of 2 years.
Real-world time to treatment discontinuation (rwTTD) in all participants
rwTTD will be calculated as the time from index date until discontinuation of treatment for any reason, including disease progression, toxicity, and death.
Measured: rwTTD will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTD for a minimum follow-up of 2 years.
Characterization of providers among all participants
Descriptive statistics will be used to describe provider characteristics: academic vs. community.
Measured: Provider characteristics will be captured up to 5 years prior to the index date
Real-world recurrence free survival (rwRFS) in aBTC and uHCC
rwRFS will be defined as the time from the index date to the earliest date of documented disease recurrence as determined by the physician's assessment or death, whichever is earlier. The analysis will be performed in patients who underwent curative therapy (resection or ablation).
Measured: rwRFS will be assessed as RFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median RFS for a minimum follow-up of 2 years.
Real-world time to recurrence (rwTTR) in aBTC and uHCC
rwTTR will be defined as the time from the index date to the date of documented disease recurrence as determined by the physician's assessment. The analysis will be performed in patients who underwent curative therapy (resection or ablation).
Measured: rwTTR will be assessed as recurrence rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTR for a minimum follow-up of 2 years.
Liver function over time in eeHCC and EMERALD
Liver function markers over time will be examined including the closest measure to the index date in the baseline period of first LRT, from pre-treatment through the follow-up period. The primary summary of interest is the change (or trajectory) in liver function markers (ALBI score and Child-Pugh score) over time.
Measured: Liver function will be assessed as the change in liver function markers for a minimum follow-up of 2 years
Provider specialty and treatment patterns in eeHCC
Provider specialty characteristics will be described. The percentage of participants receiving LRT as subsequent line of treatment (among participants receiving only LRT as standard of care).
Measured: Provider specialty will be assessed descriptively and treatment patterns will be assessed as a percentage of participants for a minimum follow-up of 2 years
Clinical characteristics in EMERALD and eeHCC
The percentage of participants who receive subsequent curative resection or liver transplant will be described.
Measured: Clinical characteristics will be assessed descriptively for a minimum follow-up of 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2024
- Study start20 Dec 2023
- Primary completion30 Dec 2030 (estimated)
- Study completion30 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatobiliary CancersStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- Other
- Enrolment
- 4,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ICON plc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06252753
- Sponsor's protocol ID
- D419CR00035
- Acronym
- LIVER-R
- Status last verified
- Sep 2026
- First submitted
- 21 Dec 2023
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Plan to share only the redacted CSR synopsis
Publications
Ikeda M, Worns MA, Akce M, Hsu C, Tebbutt NC, Casadei-Gardini A, Sah J, Farid-Kapadia M, Stirnadel-Farrant HA, Paskow MJ, Baur B, Melillo G, Schmidt J, Daktera A, Knox JJ. LIVER-R study protocol: a global real-world study of durvalumab-based regimens in patients with hepatobiliary cancers. Future Oncol. 2025 Dec;21(29):3739-3748. doi: 10.1080/14796694.2025.2589057. Epub 2025 Nov 24.
PubMed 41277677
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Multi-Center Study to Evaluate Real-World Treatment Outcomes With or Without Durvalumab-Based Regimens in Hepatobiliary Cancers
- ClinicalTrials.gov ID
- NCT06252753
- Acronym / sponsor ID
- LIVER-R / D419CR00035
- Conditions
- Hepatobiliary Cancers
- Keywords
- Hepatobiliary cancer, Unresectable hepatocellular carcinoma (uHCC), embolization eligible uHCC (eeHCC), Advanced biliary tract cancer (aBTC), Durvalumab, Observatory, Real-world
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 4,000 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- ICON plc
- Study start
- 20 Dec 2023 (actual)
- Primary completion
- 30 Dec 2030 (estimated)
- Study completion
- 30 Dec 2030 (estimated)
- First posted
- 12 Feb 2024 (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.
Given the number of anticipated durvalumab-based treatment launches in the hepatobiliary cancer space over the next 3 years, there is a need to capture contemporary real-world data across these indications. LIVER-R is a multi-country, multi-center, observational study of patients with a confirmed diagnosis of hepatobiliary cancer treated with or without a durvalumab-based regimen as part of routine clinical practice or early access program (EAP). The study design will include primary and secondary data collection. The primary objective of this study is to evaluate the effectiveness of regimens (durvalumab-based or otherwise) in real-world settings as measured by real-world overall survival. Other endpoints include demographics, clinical characteristics, clinically significant events of interest, treatment patterns, concomitant medications, treatment provider characteristics, and other real-world clinical endpoints (such as duration of treatment, progression-free survival, time to treatment progression, time to next treatment, time to treatment discontinuation, recurrence-free survival, and time to treatment recurrence ).
Detailed description
LIVER-R is a real-world, multi-country, multi-centre study aiming to enroll approximately 4,000 patients across hepatobiliary cohorts (approximately 1,385 patients for aBTC, approximately 1,165 patients for uHCC, approximately 1,000 patients for eeHCC, and approximately 400 patients for EMERALD) across multiple countries from North and South America, Europe, the Middle East and the Asia-Pacific region. The study design will include primary and secondary data collection. Primary data will be collected in real-time during the patient's routine visit. Secondary data will be collected from the patient's medical record at enrollment and at prespecified study time points (6-month intervals). The study population includes adult patients whose physician has previously made the decision to treat them with or without a durvalumab-based regimen for hepatobiliary cancer as part of routine clinical practice or patients receiving treatment through EAP. The study will include a baseline period of up to 5 years before the index date (initiation of a durvalumab-based or non durvalumab-based regimen) and a follow-up period to the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years. This is a descriptive, noncomparative study. No formal hypotheses are to be tested. All descriptive analyses will be conducted separately for each primary hepatobiliary cancer indication. Kaplan Meier estimates will be produced for time-to-event outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| unresectable hepatocellular carcinoma (uHCC) | – | Other: Durvalumab-based combination therapies in observational study settingadvanced uHCC patients who had not received prior systemic therapy and were not eligible for LRT, as well as those who had progressed following LRT, and who have received a durvalumab-based regimen |
| advanced biliary tract cancer (aBTC) | – | Other: Durvalumab-based combination therapies in observational study settingpatients with advanced BTC (aBTC) who are not eligible for resection and who have received a durvalumab-based regimen |
| eeHCC | – | Other: Non Durvalumab-based therapies in observational study settinguHCC patients with liver-confined disease not amenable to curative treatment but amenable to LRT who receive LRT alone or LRT followed by systemic therapy within 60 days (if administered in combination, LRT must be received first) |
| EMERALD | – | Other: Durvalumab-based combination therapies in observational study settingsuHCC patients with liver-confined disease not amenable to curative treatment but amenable to LRT who receive durvalumab-based regimens in combination with LRT (durvalumab and LRT are given within 28 days of each other, regardless of order) |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes patients treated with durvalumab-based and non durvalumab-based regimens for hepatobiliary cancer as part of routine clinical practice. The decision to treat patients with a durvalumab based regimen should be independent from the decision to enroll patients in the study.
Key inclusion criteria (27 listed)
- All patients must meet all of the following general criteria 1-4 along with all respective cohort specific criteria noted below:
- Age ≥18 years and a lawful adult in the country at the index date
- Confirmed presence of malignancy of primary hepatobiliary cancer by any method (e.g., radiological, histological, etc.)
- Decision to treat was made independently and prior to obtaining informed consent
- Informed consent was obtained as per country level regulations (includes waiver of consent for retrospective data collection if approved)
Key exclusion criteria (26 listed)
- General Exclusion Criteria
- A patient will be excluded from participating in this study if they meet any of the following general criteria 1-2 or any cohort specific exclusion criteria:
- Currently/was participating or plans to participate in any clinical trial for investigational treatment for hepatobiliary cancers on or after the diagnosis date until the index date
- Second primary malignancy prior to HCC or BTC diagnosis
- aBTC Specific Exclusion Criteria
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 |
|---|---|---|
| Durvalumab-based combination therapies in observational study settingAlso: ImfinziData on patients who initiated durvalumab-based regimens, including STRIDE (Single Tremelimumab Regular Interval Durvalumab), will be collected). | Other | unresectable hepatocellular carcinoma (uHCC) |
| Durvalumab-based combination therapies in observational study settingAlso: ImfinziData on patients who initiated durvalumab-based regimens, including durvalumab + chemotherapy combinations (e.g., Durvalumab + GemCis etc.) will be collected. | Other | advanced biliary tract cancer (aBTC) |
| Non Durvalumab-based therapies in observational study settingData on patients who initiated non durvalumab-based regimens, including LRT alone or LRT followed by systemic therapies, will be collected. | Other | eeHCC |
| Durvalumab-based combination therapies in observational study settingsAlso: ImfinziData on patients who initiated durvalumab-based regimens in combination with LRT, will be collected | Other | EMERALD |
Primary outcome
Real-world overall survival (rwOS) in all participants
Time frame: rwOS will be assessed as OS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median OS for a minimum follow-up of 2 years.
rwOS will be calculated as the time from the index date to date of death, by any cause.
14 secondary outcomes
Clinically significant events (CSEs) of interest leading to a medical intervention in all participants
Time frame: CSEs will be captured from the index date through 90 days after the last administration of durvalumab-based or non durvalumab-based regimens or death, whichever occurs first.
Patient demographic and clinical characteristics in all participants
Time frame: Patient demographic and clinical characteristics will be captured up to 5 years prior to the index date.
Characterize the durvalumab-based regimen and/or LRT treatment patterns in all participants
Time frame: Treatment patterns will be captured from the index date until the earliest of death, loss to follow-up, withdrawal, or end of study for a minimum follow-up of 2 years.
Real-world duration of treatment (rwDOT) in all participants
Time frame: rwDOT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median DOT for a minimum follow-up of 2 years.
Real-world progression free survival (rwPFS) in all participants
Time frame: rwPFS will be assessed as PFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median PFS for a minimum follow-up of 2 years.
Real-world time to progression (rwTTP) in all participants
Time frame: rwTTP will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTP for a minimum follow up of 2 years.
Real-world time to next treatment (rwTTNT) in all participants
Time frame: rwTTNT will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTNT for a minimum follow-up of 2 years.
Real-world time to treatment discontinuation (rwTTD) in all participants
Time frame: rwTTD will be assessed as event rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTD for a minimum follow-up of 2 years.
Characterization of providers among all participants
Time frame: Provider characteristics will be captured up to 5 years prior to the index date
Real-world recurrence free survival (rwRFS) in aBTC and uHCC
Time frame: rwRFS will be assessed as RFS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median RFS for a minimum follow-up of 2 years.
Real-world time to recurrence (rwTTR) in aBTC and uHCC
Time frame: rwTTR will be assessed as recurrence rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median TTR for a minimum follow-up of 2 years.
Liver function over time in eeHCC and EMERALD
Time frame: Liver function will be assessed as the change in liver function markers for a minimum follow-up of 2 years
Provider specialty and treatment patterns in eeHCC
Time frame: Provider specialty will be assessed descriptively and treatment patterns will be assessed as a percentage of participants for a minimum follow-up of 2 years
Clinical characteristics in EMERALD and eeHCC
Time frame: Clinical characteristics will be assessed descriptively for a minimum follow-up of 2 years.
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 25 Sep 2026.
- Background: PubMed 41277677Ikeda M, Worns MA, Akce M, Hsu C, Tebbutt NC, Casadei-Gardini A, Sah J, Farid-Kapadia M, Stirnadel-Farrant HA, Paskow MJ, Baur B, Melillo G, Schmidt J, Daktera A, Knox JJ. LIVER-R study protocol: a global real-world study of durvalumab-based regimens in patients with hepatobiliary cancers. Future Oncol. 2025 Dec;21(29):3739-3748. doi: 10.1080/14796694.2025.2589057. Epub 2025 Nov 24.
- Individual participant dataSharing planned: Yes. Plan to share only the redacted CSR synopsis
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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.
AstraZeneca Clinical Study Information Center contact
160 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatobiliary Cancers, run by AstraZeneca at 160 sites in 22 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 27 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 160 sites in Germany, United States, Spain, France, Italy and 17 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?
Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Real-world overall survival (rwOS) in all participants (time frame: rwOS will be assessed as OS rates at 6, 12, 18, 24, and 36 months, as applicable per the type of hepatobiliary cancer; median OS for a minimum follow-up of 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06252753, which also lists 1 linked publication.
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 25 Sep 2026.