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Carcinoma, HepatocellularPhase 3RESORCENCT01774344

Study of Regorafenib After Sorafenib in Patients With Hepatocellular Carcinoma

A Phase 3 study testing Regorafenib (Stivarga, BAY73-4506) in people with Carcinoma, Hepatocellular, run by Bayer at 147 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The objective of this study was to evaluate efficacy and safety of regorafenib in patients with advanced liver cancer who had progressed after sorafenib treatment. Patients were treated with regorafenib or placebo using a 2:1 randomization scheme. 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 (Stivarga, BAY73-4506)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
573 participants
Where
147 sitesin 21 countries
Study dates
14 May 2013to 5 Jul 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histological or cytological confirmation of HCC (hepatocellular carcinoma) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases criteria in patients with a confirmed diagnosis of cirrhosis
  • Barcelona Clinic Liver Cancer stage Category B or C that cannot benefit from treatments of established efficacy with higher priority such as resection, local ablation, chemoembolization or systemic sorafenib.
  • Failure to prior treatment with sorafenib (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 10 weeks after the last treatment with sorafenib.
  • Tolerability of prior treatment with sorafenib defined as not less than 20 days at a minimum daily dose of 400 mg QD within the last 28 days prior to withdrawal.
  • Liver function status Child-Pugh Class A. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
  • Local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >/=4 weeks before first dose of study medication. Note: patients who received sole intrahepatic intraarterial chemotherapy, without lipiodol or embolizing agents are not eligible.
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  • Eastern Cooperative Oncology Group Performance Status of 0 or 1.
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted within 7 days before randomization.
  • Glomerular filtration rate >/= 30 ml/min/1.73 m^2 according to the Modification of diet in renal disease study equation.
  • At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST (RECIST version 1.1), and modified RECIST for HCC. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion.
  • Life expectancy of at least 3 months.
  • Women of childbearing potential and men must agree to use adequate contraception .

Who cannot join

  • Sorafenib treatment within 2 weeks of randomization.
  • Prior systemic treatment for HCC, except sorafenib.
  • Permanent discontinuation of prior sorafenib therapy due to sorafenib related toxicity.
  • Known history or symptomatic metastatic brain or meningeal tumors (head CT or MRI at screening to confirm the absence of central nervous system [CNS] disease if patient has symptoms suggestive or consistent with CNS disease).
  • Uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
  • Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis treatment).
Show all 11Show fewer
  • Ongoing infection > Grade 2 according to NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) v. 4.0. Hepatitis B is allowed if no active replication is present. Hepatitis C is allowed if no antiviral treatment is required.
  • Clinically significant bleeding NCI-CTCAE version 4.0 Grade 3 or higher within 30 days before randomization.
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication.
  • Patients unable to swallow oral medications.
  • Interstitial lung disease with ongoing signs and symptoms at the time of screening.

Trial locations and contacts

147 sites in 21 countries.

147 sites in 21 countries

China25 sites

  • Study site

    Beijing, 100039

  • Study site

    Beijing, 100069

  • Study site

    Beijing, 100071

  • Study site

    Beijing, 100142

  • Study site

    Changsha, Hunan, 410013

  • Study site

    Chengdu, Sichuan, 610041

  • Study site

    Chongqing, 400038

  • Study site

    Dalian, Liaoning, 116011

  • Study site

    Fuzhou, Fujian, 350025

  • Study site

    Guangzhou, Guangdong, 510060

  • Study site

    Guangzhou, Guangdong, 510080

  • Study site

    Guangzhou, Guangdong, 510515

  • Study site

    Harbin, Heilongjiang, 150081

  • Study site

    Hefei, Anhui, 230022

  • Study site

    Nanjing, Jiangsu, 210002

  • Study site

    Nanning, Guangxi, 530021

  • Study site

    Shanghai, 200001

  • Study site

    Shanghai, 200032

  • Study site

    Shanghai, 201805

  • Study site

    Suzhou, Jiangsu, 215006

  • Study site

    Tianjin, 300060

  • Study site

    Wuhan, Hubei, 430030

  • Study site

    Xi'an, Shaanxi, 710032

  • Study site

    Xi'an, Shaanxi, 710038

  • Study site

    Xi'an, Shaanxi, 710061

Other trials in China

France19 sites

  • Study site

    Angers, 49100

  • Study site

    Caen, F-14033

  • Study site

    Clichy, 92110

  • Study site

    Créteil, 94010

  • Study site

    Dijon, 21000

  • Study site

    La Tronche, 38700

  • Study site

    Lille, 59037

  • Study site

    Lyon, 69004

  • Study site

    Marseille, 13005

  • Study site

    Montpellier, 34295

  • Study site

    Nice, 06202

  • Study site

    Paris, 75020

  • Study site

    Paris, 75651

  • Study site

    Perpignan, 66000

  • Study site

    Reims, 51092

  • Study site

    Rennes, 35062

  • Study site

    Toulouse, 31059

  • Study site

    Vandœuvre-lès-Nancy, 54500

  • Study site

    Villejuif, 94805

Other trials in France

United States17 sites

  • Study site

    Aurora, Colorado, 80045

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Gainesville, Florida, 32610-0286

  • Study site

    Los Angeles, California, 90048

  • Study site

    Los Angeles, California, 90095

  • Study site

    Louisville, Kentucky, 40202

  • Study site

    Minneapolis, Minnesota, 55455

  • Study site

    New York, New York, 10029

  • Study site

    Orange, California, 92868-3201

  • Study site

    Pittsburgh, Pennsylvania, 15232

  • Study site

    Richmond, Virginia, 23249

  • Study site

    Rochester, New York, 14642

  • Study site

    Seattle, Washington, 98101

  • Study site

    St Louis, Missouri, 63110

  • Study site

    Tampa, Florida, 33606

  • Study site

    Washington D.C., District of Columbia, 20007-2197

  • Study site

    Worcester, Massachusetts, 01655

Other trials in United States

Italy14 sites

  • Study site

    Bergamo, Lombardy, 24127

  • Study site

    Bologna, Emilia-Romagna, 40138

  • Study site

    Cagliari, Sardinia, 09134

  • Study site

    Foggia, Apulia, 71013

  • Study site

    Genoa, Liguria, 16132

  • Study site

    Milan, Lombardy, 20089

  • Study site

    Milan, Lombardy, 20122

  • Study site

    Modena, Emilia-Romagna, 41124

  • Study site

    Naples, Campania, 80131

  • Study site

    Novara, Piedmont, 28100

  • Study site

    Padova, Veneto, 35128

  • Study site

    Pisa, Tuscany, 56126

  • Study site

    Rome, Lazio, 00168

  • Study site

    Turin, Piedmont, 10126

Other trials in Italy

Japan12 sites

  • Study site

    Chiba, Chiba, 260-8677

  • Study site

    Chiyoda-ku, Tokyo, 101-0062

  • Study site

    Chuo-ku, Tokyo, 104-0045

  • Study site

    Fukuoka, Fukuoka, 810-8563

  • Study site

    Iizuka-shi, Fukuoka, 820-8505

  • Study site

    Kashiwa-shi, Chiba, 277-8577

  • Study site

    Kumamoto, Kumamoto, 860-8556

  • Study site

    Musashino-shi, Tokyo, 180-8610

  • Study site

    Osaka, Osaka, 541-8567

  • Study site

    Osakasayama-shi, Osaka, 589-8511

  • Study site

    Utsunomiya, Tochigi, 321-0974

  • Study site

    Yokohama, Kanagawa, 232-0024

Other trials in Japan

Germany11 sites

  • Study site

    Aachen, North Rhine-Westphalia, 52074

  • Study site

    Berlin, 13353

  • Study site

    Cologne, North Rhine-Westphalia, 50937

  • Study site

    Essen, North Rhine-Westphalia, 45136

  • Study site

    Frankfurt am Main, Hesse, 60590

  • Study site

    Hamburg, 20246

  • Study site

    Hanover, Lower Saxony, 30625

  • Study site

    Heidelberg, Baden-Wurttemberg, 69120

  • Study site

    Magdeburg, Saxony-Anhalt, 39120

  • Study site

    Mainz, Rhineland-Palatinate, 55131

  • Study site

    München, Bavaria, 81377

Other trials in Germany

Spain9 sites

  • Study site

    Alicante, 03010

  • Study site

    Barcelona, 08035

  • Study site

    Barcelona, 08036

  • Study site

    Córdoba, 14004

  • Study site

    Madrid, 28007

  • Study site

    Madrid, 28041

  • Study site

    Madrid, 28050

  • Study site

    Oviedo, Principality of Asturias, 33011

  • Study site

    Zaragoza, 50009

Other trials in Spain

Australia5 sites

  • Study site

    Box Hill, 3128

  • Study site

    Camperdown, New South Wales, 2050

  • Study site

    Clayton, Victoria, 3168

  • Study site

    Herston, Queensland, 4029

  • Study site

    Liverpool, New South Wales, 2170

Other trials in Australia

United Kingdom5 sites

  • Study site

    Birmingham, West Midlands, B15 2WB

  • Study site

    Bristol, BS2 8ED

  • Study site

    Leeds, West Yorkshire, LS9 7TF

  • Study site

    London, SE5 9RS

  • Study site

    London, W12 0HS

Other trials in United Kingdom

South Korea4 sites

  • Study site

    Busan, Busan Gwang''yeogsi, 49241

  • Study site

    Daegu, 700-721

  • Study site

    Seoul, 06351

  • Study site

    Seoul, 110-744

Other trials in South Korea

Taiwan4 sites

  • Study site

    Kaohsiung City, Kaohsiung, 83301

  • Study site

    Taipei, 10016

  • Study site

    Taipei, 11217

  • Study site

    Taoyuan, 333

Other trials in Taiwan

Austria3 sites

  • Study site

    Graz, Styria, 8036

  • Study site

    Linz, Upper Austria, 4020

  • Study site

    Vienna, 1090

Other trials in Austria

Czechia3 sites

  • Study site

    Hradec Králové, 500 05

  • Study site

    Olomouc, 775 20

  • Study site

    Prague, 128 08

Other trials in Czechia

Hungary3 sites

  • Study site

    Budapest, 1097

  • Study site

    Debrecen, 4032

  • Study site

    Kaposvár, 7400

Other trials in Hungary

Russia3 sites

  • Study site

    Barnaul, 656045

  • Study site

    Moscow, 119991

  • Study site

    Moscow

Other trials in Russia

Belgium2 sites

  • Study site

    Bruxelles - Brussel, 1090

  • Study site

    La Louvière, 7100

Other trials in Belgium

Brazil2 sites

  • Study site

    Salvador, Estado de Bahia, 41950-610

  • Study site

    São Paulo, 05403-000

Other trials in Brazil

Netherlands2 sites

  • Study site

    Amsterdam, 1105 AZ

  • Study site

    Leiden, 2333 ZA

Other trials in Netherlands

Switzerland2 sites

  • Study site

    Bellinzona, Canton Ticino, 6500

  • Study site

    Bern, 3010

Other trials in Switzerland

Argentina1 site

  • Study site

    Pilar, Buenos Aires, B1629ODT

Other trials in Argentina

Singapore1 site

  • Study site

    Singapore, 119228

Other trials in Singapore

About this study

Official title: A Randomized, Double Blind, Placebo Controlled, Multicenter Phase III Study of Regorafenib in Patients With Hepatocellular Carcinoma (HCC) After Sorafenib

The objective of this study was to evaluate efficacy and safety of regorafenib in patients with advanced liver cancer who had progressed after sorafenib treatment. Patients were treated with regorafenib or placebo using a 2:1 randomization scheme.

Being tested
Regorafenib (Stivarga, BAY73-4506), Placebo
Keywords
Regorafenib, BAY73-4506
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 (Stivarga, BAY73-4506)Drug

    Regorafenib, 40 mg tablets

  • PlaceboDrug

    Placebo tablets matching in appearance

Study groups in NCT01774344
Study groupRoleWhat they receive
RegorafenibExperimental160 mg orally (p.o.) every day (qd) for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC (Best Supportive Care)
Receives: Drug: Regorafenib (Stivarga, BAY73-4506)
PlaceboPlacebo comparator4 matching placebo tablets for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    Overall Survival (OS) was defined as the time from date of randomization (Day 1) to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.

    Measured: From randomization (Day 1) of the first subject until 419 days later

Secondary outcomes (4)

  1. Time to Progression (TTP)

    TTP was the time (days) from randomization to radiological or clinical disease progression assessed by independent radiological review. Median and 95% confidence interval were reported for the modified response evaluation criteria in solid tumors (mRECIST) and response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) analysis sets. Subjects still alive at the time of analysis were censored at their last date of last contact.

    Measured: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)

  2. Progression Free Survival (PFS)

    Progression Free Survival (PFS) was defined as the time (days) from date of randomization to date of disease progression (radiological or clinical) or death due to any cause, if death occurs before progression was documented. Death in the absence of progression was a PFS event only if it occurred within the 12+1 weeks for subjects who discontinued treatment prior to cycle 8 and 24+2 weeks for subjects who discontinued treatment after to cycle 8 of the last evaluable tumor assessment; PFS were censored at the date of the last evaluable tumor assessment, if it occurred later. Median and 95% confidence interval 95% were reported for the mRECIST and RECIST 1.1 analysis sets. Subjects still alive at the time of analysis were censored at their last date of last contact.

    Measured: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks)

  3. Objective Tumor Response Rate (ORR)

    Objective tumor response rate (ORR) was defined as the percentage of subjects whose best tumor response CR or Partial Response (PR) observed during trial period assessed according to the mRECIST criteria and RECIST 1.1. CR= Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Subjects prematurely discontinuing without an assessment were to be considered non-responders for the analysis.

    Measured: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)

  4. Disease Control Rate (DCR)

    Disease control rate (DCR) was defined as the percentage of subjects whose best response was CR (CR: disappearance of all clinical and radiological evidence of tumor (both target and non-target).), PR (PR: at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.), or stable disease (SD) (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non-target lesions, and no appearance of new lesions.) according to RECIST and RECIST 1.1 criteria. SD had to be maintained for at least 6 weeks from the first demonstration of that rating.

    Measured: From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jan 2013 (estimated)
  2. Study start14 May 2013
  3. Primary completion29 Feb 2016
  4. Study completion5 Jul 2019

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
573 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01774344
Sponsor's protocol ID
15982
Other IDs
2012-003649-14
Acronym
RESORCE
Status last verified
Aug 2020
First submitted
21 Jan 2013
Last updated
20 Aug 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.

Publications

  • Finn RS, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Gerolami R, Caparello C, Cabrera R, Chang C, Sun W, LeBerre MA, Baumhauer A, Meinhardt G, Bruix J. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial. J Hepatol. 2018 Aug;69(2):353-358. doi: 10.1016/j.jhep.2018.04.010. Epub 2018 Apr 26.

    PubMed 29704513

  • Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. doi: 10.1016/S0140-6736(16)32453-9. Epub 2016 Dec 6.

    PubMed 27932229

  • Wu W, Mao H, Song J, Yang F. Bibliometric analysis of hepatocellular carcinoma and tyrosine kinase inhibitors. Medicine (Baltimore). 2025 May 16;104(20):e42015. doi: 10.1097/MD.0000000000042015.

    PubMed 40388796

  • Teufel M, Seidel H, Kochert K, Meinhardt G, Finn RS, Llovet JM, Bruix J. Biomarkers Associated With Response to Regorafenib in Patients With Hepatocellular Carcinoma. Gastroenterology. 2019 May;156(6):1731-1741. doi: 10.1053/j.gastro.2019.01.261. Epub 2019 Feb 6.

    PubMed 30738047

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Regorafenib (Stivarga, BAY73-4506) in people with Carcinoma, Hepatocellular, run by Bayer at 147 sites in 21 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 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 147 sites in China, France, United States, Italy, Japan and 16 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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: From randomization (Day 1) of the first subject until 419 days later). 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 NCT01774344, which also lists 4 linked publications.

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 20 Aug 2020.

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